Major Depressive DisorderPhase 1NCT02869035
Treatment Outcome in Major Depressive Disorder
A Phase 1 study testing Escitalopram and Duloxetine in people with Major Depressive Disorder, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
Major Depressive Disorder (MDD) is one of the most severe and frequently occurring brain disorders worldwide. It has been linked to serotonergic dysfunction, sexual dysfunction, vulnerability to stress and neuro-inflammation. However, at the same time the etiological understanding is limited. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Escitalopram and Duloxetine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteDenmark
- Study dates
- Aug 2016to Jul 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Moderate to severe depression
- Age 18-65 years
- No previous antidepressant treatment the last 2 months
- Informed and signed consent
Who cannot join
- More than one previous attempt with antidepressant drugs
- Duration of current depression more than 2 years
- Current or previous psychiatric severe co-morbidity
- Acute suicidal ideation
- Psychotic
- Previous non-response to Selective Serotonin Reuptake Inhibitor (SSRI)
Show all 17Show fewer
- Contraindication for SSRI treatment
- More suitable with treatment of alternative anti-depressive drug.
- Severe somatic co-morbidity
- Somatic medicine that can influence the trial
- Contraindications for MR-scanning
- Previous exposure to radioactivity > 10 milli sievert (mSv) within the last year
- Alcohol or drug abuse
- Previous severe head trauma
- Pregnancy
- Breast-feeding
- Insufficient Danish skills
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Predicting Treatment Outcome in Major Depressive Disorder
Major Depressive Disorder (MDD) is one of the most severe and frequently occurring brain disorders worldwide. It has been linked to serotonergic dysfunction, sexual dysfunction, vulnerability to stress and neuro-inflammation. However, at the same time the etiological understanding is limited. Most antidepressants act on the serotonin (5- HT) system, yet between 30-50 % of patients with MDD does not respond successfully to 5-HT acting drugs. Recent experimental models from our group suggest that cerebral 5-HT levels in vivo can be indexed through molecular brain imaging of the 5-HT 4 receptor (5-HT4R) with a novel Positron Emission Tomography (PET) ligand (11C-SB207145). Also, our human studies have confirmed that cerebral synaptic 5-HT is inversely related to 5-HT4R binding and this technique thus can be used to investigate the role of 5-HT tone in the brain in MDD with differential responses to standard antidepressant treatment. By using multimodal neuroimaging technology, we aim to determine the status of the 5-HT system prior to and after either successful or failed neuropharmacological intervention in a non-randomized longitudinal open clinical trial. 100 untreated patients with moderate to severe MDD will be included. Data collection from various neurobiological domains (i.e, 5-HT4R PET imaging, Magnetic Resonance Imaging (MRI), functional MRI (fMRI), electroencephalogram (EEG), psychometrics, neuropsychological tests, and peripheral biomarkers) will be conducted before, during and after 12 weeks of antidepressant treatment. The objective is to identify predictors of pharmacological antidepressant treatment response in depressed individuals before and after 8 weeks of antidepressant treatment.
Read the detailed description
Study population and study program:
Patients will be recruited through a unique new central referral site for "depression packages" in The Mental Health Services in the Capital Region of Denmark. 100 patients with MDD, 18-65 years of age, with moderate to severe single or recurrent episode of MDD (Hamilton 17 item (HAMD-17) score > 17) will be recruited through this portal. All diagnoses will be confirmed by a specialist in psychiatry.
Before initiation of pharmacological antidepressant treatment with escitalopram, patients will receive baseline examinations as follows: 1) 5-HT4R imaging with 11C-SB207145 PET-scan, 2) EEG examinations, 3) structural MRI, 4) functional MRI , 5) neuropsychological testing, 6) peripheral markers of immune-active cell responses, oxidative stress, cortisol-levels, RNA, genotypes and epigenetic factors will be measured in urine, saliva and peripheral blood at baseline and across the study period. Repeated measures across the study period include: 7) psychometrics by using self-reported questionnaires covering trait and state, including mental distress related to depression and other psychopathology, 8) neuropsychological examinations as well as 9) clinical follow-up with interview based ratings of mental status.
Patients will be treated with escitalopram at flexible doses of 10-20 mg/day adjusted depending on effects and side effects, and participate in clinical follow-up sessions at week 1, 2, 4 and 8. Patients with no response to escitalopram after 4 weeks will be shifted to a secondary pharmacological treatment (duloxetine). A final visit to determine longer-term clinical outcome will be performed at week 12. Compliance, side-effects to antidepressant treatment, and depressive symptoms will be monitored at each follow-up session.
The Hamilton 6 items (HAMD-6) subscale has recently shown to be more sensitive to antidepressant response (Østergaard et al), and will be used to identify treatment response in patients. Patients with > 50 % reduction in HAMD-6 after 4 weeks will be defined as early responders, and those with additional < 5 points on the HAMD-6 scale after 8 weeks will be considered in remission. Patients with >25% response at week 4 and < 50% reduction in HAMD-6 after full intervention will be considered non-responders. The assessment program including brain imaging with PET 11C-SB207145 will be conducted before drug intervention is initiated and, depending on treatment outcome, again after 8 weeks of antidepressant treatment in 20 patients in remission (remitters) and 20 non-responding patients (non-responders).
UPDATE: As per April 3, 2017 the rescanned group has been expanded to include various response patterns in order to capture rescan data from patients on a spectrum from poor to excellent treatment response, since out of the first 17 included patients only 1 patient fulfilled the non-responder criterion defined above. Accordingly, the clinical outcome parameter in the context will be changes in HAM-D6 from baseline at week 8.
Healthy controls:
From previous studies conducted at the Neurobiological Research Unit, there is access to brain imaging data and baseline PET-SB207145 brain images among healthy controls as well as an associated biobank with stored blood specimens. During the trial, additional healthy controls will be included and will receive baseline examinations and repeated neuropsychological testing after 12 weeks.
Hypotheses:
- 5-HT4R binding (as imaged by 11C-SB207145 PET) before treatment will predict antidepressant treatment outcome (remission vs non-response) in depressed patients; higher binding at baseline is hypothesized to be associated with a better treatment outcome. Likewise, secondary, 5-HT4R binding (as imaged by 11C-SB207145 PET) before treatment is expected to be associated with the magnitude of change from baseline in Hamilton score (HAMD-6) at 8 weeks.
- Remitters will display a greater reduction in 5-HT4R binding (as imaged by 11C-SB207145 PET) after antidepressant treatment relative to non-responders.
- Patients with MDD will have a higher 5-HT4R binding (as imaged by 11C-SB207145 PET) relative to healthy controls.
- High amygdala reactivity in an "emotional faces" fMRI paradigm before treatment predicts remission in response to antidepressant treatment.
- Amygdala response to exposure to negative emotional faces (fear and anger) and cerebral 5-HT4R binding is expected to be associated, both in cross-sectional comparison before treatment and with regard to longitudinal changes (changes from baseline).
- In resting state fMRI (rsfMRI), we expect that changes from baseline in a functional network centered around dorsomedial prefrontal cortex and other networks centered around anterior cingulate cortex and posterior cingulate cortex (default mode network) respectively will predict treatment outcome.
- Low activity in a brain network engaged in reward processing (as assessed by fMRI) will predict antidepressant treatment response (i.e. positive association between low activity and remitter- relative to non-responder group) both in cross-sectional comparison before treatment and with regard to longitudinal changes (changes from baseline).
- We expect reduced evoked gamma-activity measured with EEG and "Event-related-potentials" (ERP) in MDD patients compared to controls.
- Using EEG/ERP, we expect reduced alpha and theta cordance and higher theta band activity among remitters measured at baseline.
- Higher levels of systemic inflammation will predict poor cognitive function at baseline, and a poor antidepressant treatment outcome.
- A blunted cortisol awakening response (CAR) at baseline will predict a positive antidepressant treatment outcome.
- Restored HPA-axis dynamics (increased CAR compared to baseline) at week 8 will be associated with a positive treatment outcome.
- There will be a significant association between functional networks found by EEG and fMRI, both at baseline and as contrast between remitters and non-responders after 8 weeks.
- Hippocampal volume will predict treatment outcome.
- Patients with a low 5-HT4R binding (as imaged by 11C-SB207145 PET) at baseline before treatment will have a lower libido relative to patients with a high binding.
- Patients who respond to antidepressant treatment with the most pronounced changes in 5-HT4R binding (as imaged by 11C-SB207145) will experience a larger degree of sexual side-effects; i.e., the magnitude of 5-HT4R binding changes from baseline will be positively associated with the degree of sexual side-effects.
- Childhood abuse (defined by a composite measure of early life stress questionnaires) and anxious depression (defined as anxiety/somatization factor score in HAMD-17 > 7) predicts poor antidepressant treatment outcome.
- We expect urinary markers of oxidatively generated DNA/RNA damage to increase more in responders than in non-responders.
- With an exploratory approach it will be possible to identify a set of predictors of antidepressant treatment outcome. This explorative analysis includes genetics, epigenetics, peripheral and central neurobiological characteristics, neuropsychology testing outcomes, psychometry including self-reported mental distress, both cross-sectional at baseline and as longitudinal measures.
Ethical Aspects:
The study protocol complies with the Declaration of Helsinki II and approval by all relevant authorities will be obtained before initiation. All human volunteers will receive oral and written information about the given study and provide written informed consent before enrolment. The trial is monitored by a Good Clinical Practise unit for the relevant domains.
- Conditions
- Major Depressive Disorder
- Being tested
- Escitalopram, Duloxetine
- Keywords
- PET, Serotonin, 5-HT4R, MRI, fMRI, EEG, Cortisol awakening response, Oxidative stress, Mental health, Prediction of treatment response, Inflammation, 5-HTTLPR, Brain imaging, Early life stress, Selective Serotonin Reuptake Inhibitor, Escitalopram, Psychometrics, Moderate depression, Severe depression, ERP
- Medical subject headings
- Depressive Disorder, Major, Psychological Well-Being, Inflammation, Stress, Psychological, Depression, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EscitalopramDrug
Patients will be treated with an antidepressant drug (escitalopram) at flexible standard doses for 12 weeks. If no response after 4 weeks; shift to duloxetine arm.
DuloxetineDrug
Patients who at 4 weeks of escitalopram have not responded will be shifted to duloxetine at flexible standard dosages.
| Study group | Role | What they receive |
|---|---|---|
| Treatment of MDD patients | Experimental | Treatment of MDD patients with escitalopram Receives: Drug: Escitalopram |
| Healthy controls | No intervention | No treatment. |
| Shift of treatment for MDD patients | Experimental | Treatment of MDD patients with duloxetine Receives: Drug: Duloxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Binary treatment outcome in terms of remission from depression.
Treatment outcome defined as changes in HAMD-6 score after antidepressant treatment (remitters and non-responders as previously defined).
Measured: Baseline to clinical follow-up at 8 weeks after antidepressant treatment.
Baseline cerebral 5-HT4R binding as imaged by 11C-SB207145 PET.
Latent variable construct of 5-HT4R level based on quantification of 5-HT4R binding in primary volumes of interest; neocortex, nucleus caudatus, putamen and hippocampus. Assessed in depressed patients and healthy controls.
Measured: Baseline.
Changes from baseline in cerebral 5-HT4R binding as imaged by 11C-SB207145 PET
Difference in latent variable construct of 5-HT4R level based on quantification of 5-HT4R binding in primary volumes of interest; neocortex, nucleus caudatus, putamen and hippocampus. Measured in remitters and non-responders.
Measured: Baseline to follow-up scan at 8 weeks after antidepressant treatment.
Baseline hippocampus volume
Structural MRI scan in depressed patients and healthy controls.
Measured: Baseline.
Changes from baseline in hippocampus volume.
Structural MRI in remitters and non-responders.
Measured: Baseline to follow-up scan at 8 weeks after antidepressant treatment.
Baseline fMRI BOLD response to an emotional faces paradigm
fMRI (BOLD response) based assessment of brain activity to emotionally salient, relative to neutral, stimuli.
Measured: Baseline
Changes from baseline in fMRI BOLD response to an emotional faces paradigm
fMRI (BOLD response) based assessment of brain activity to emotionally salient, relative to neutral, stimuli.
Measured: Baseline to follow-up scan at 8 weeks after antidepressant treatment.
Baseline fMRI BOLD response to reward paradigm.
fMRI (BOLD response) based assessment of brain activity in response to reward, relative to non-reward, stimuli.
Measured: Baseline
Changes from baseline in fMRI BOLD response to reward paradigm
fMRI (BOLD response) based assessment of brain activity in response to reward, relative to non-reward, stimuli.
Measured: Baseline to follow-up scan at 8 weeks after antidepressant treatment.
Baseline rsfMRI based spontaneous co-fluctuations in low frequency BOLD signal (functional connectivity)
Assessed with rsfMRI scan in the resting state, i.e. non-goal oriented spontaneous thought and awake.
Measured: Baseline
Changes from baseline in rsfMRI spontaneous co-fluctuations in low frequency BOLD signal (functional connectivity)
Assessed with rsfMRI scan in the resting state, i.e. non-goal oriented spontaneous thought and awake.
Measured: Baseline to follow-up scan at 8 weeks after antidepressant treatment.
Sexual function in depression
Assessed with scores of self reported sexual function questionnaires in depressed patients and healthy controls.
Measured: Baseline
Changes in sexual function
Questionnaire-based self-reported sexual function in remitters and non-responders
Measured: Baseline to clinical follow-up at 8 or 12 weeks after antidepressant treatment, and baseline to follow-up scan at 8 weeks after antidepressant treatment.
Baseline EEG including event related potentials (ERP)
Assessment of evoked gamma activity, alpha and theta cordance band activity in depressed patients and healthy controls.
Measured: Baseline
Changes in EEG including event related potentials (ERP)
Assessment of evoked gamma activity, alpha and theta cordance band activity in remitters and non-responders.
Measured: Baseline to follow-up examination at 8 weeks after antidepressant treatment.
Cortisol awakening response
Cortisol changes in response to awakening as measured in saliva from 0 to 60 minutes after awakening in depressed patients and healthy controls.
Measured: Baseline
Changes in cortisol awakening response (HPA-axis dynamics)
Measured in remitters and non-responders.
Measured: Baseline and follow-up examination at 8 weeks after antidepressant treatment.
Systemic inflammation peripheral blood hsCRP and immunoactive cytokines
Measured with peripheral blood markers in plasma by high-sensitivity (hs) methods.
Measured: Baseline and follow-up examination at 8 weeks after antidepressant treatment.
Changes in systemic inflammation peripheral blood hsCRP and immunoactive cytokines
Measured with peripheral blood markers in plasma by high-sensitivity (hs) methods.
Measured: Baseline and follow-up examination at 8 weeks after antidepressant treatment.
Systemic oxidative stress in terms of 8-oxodG and 8-oxoGuo in urine
8-oxodG and 8-oxoGuo measured with mass spectrometry in spot-urine and normalized to urinary creatinine, in depressed patients and healthy controls.
Measured: Baseline
Changes in systemic oxidative stress in terms of 8-oxodG and 8-oxoGuo in urine
8-oxodG and 8-oxoGuo measured with mass spectrometry in spot-urine and normalized to urinary creatinine, in remitters and non-responders.
Measured: Baseline and follow-up examinations at 8 weeks after antidepressant treatment.
Early life Stress
Self-reported early life stress with the Children Abuse and Trauma Scale (CATS) questionnaire.
Measured: Baseline
Performance on Verbal Affective Memory Tasks (VAMT-26).
Differences between healthy controls and depressed patients at baseline and week 12 follow-up, as well as longitudinal alterations to treatment response in MDD patients.
Measured: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Performance on Moral Judgement Task
Differences between healthy controls and depressed patients at baseline and week 12 follow-up, as well as longitudinal alterations to treatment response in MDD patients.
Measured: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Performance on Letter-Number Sequence Task.
Differences between healthy controls and depressed patients at baseline and week 12 follow-up, as well as longitudinal alterations to treatment response in MDD patients.
Measured: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Secondary outcomes (21)
Changes from baseline in HAMD-6 score
Score indexing changes in severity of the depressed state
Measured: Baseline to follow-up at 8 and 12 weeks
HAMD-6 score after 8 and 12 weeks of antidepressant treatment
Score indexing severity of the depressed state
Measured: Week 8 and 12 of treatment period
Regional 5-HT4R binding
Measurement of 5-HT4R binding in (a) striatum (caudate nuclei and putamen), (b) a pooled limbic region (amygdala, hippocampus, thalamus, anterior- and posterior cingulate cortex,) (c) a pooled neocortex region (parietal cortex, occipital cortex, lateral temporal cortex, insula, orbito-frontal and lateral-frontal cortex).
Measured: Measured at baseline and after 8 weeks of antidepressant treatment.
Sexual side-effects from antidepressant treatment
Perceived side effects from self reported questionnaires
Measured: 8 weeks of antidepressant treatment
Baseline latent variable construct of self-reported mental state
Composed by latent variable structural equation modelling of self-reported mental state from questionnaires score of: Becks Depression Inventory -II (BDI-II), Perceived Stress Scale (PSS), Snaith-Hamilton Pleasure Scale (SHAPS), Rumination Response Scale (RRS), Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Distress Assessment 10 item (GAD-10), Activity level, Profile of Mood States (POMS), Visual Analogue Scale for mental distress (VAS) and Brief symptom Inventory-53 item (BSI-53)) in depressed patients and healthy controls.
Measured: Baseline
Baseline self reported family history of mood disorders
Family History Assessment Module (OS-FHAM) in depressed patients and healthy controls.
Measured: Baseline
Changes from baseline in self-reported mental state questionnaire-based latent variable construct
Composed by latent variable structural equation modelling of changes from baseline in self-reported mental state from questionnaires score of: Becks Depression Inventory -II (BDI-II), Perceived Stress Scale (PSS), Snaith-Hamilton Pleasure Scale (SHAPS), Rumination Response Scale (RRS), Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Distress Assessment 10 item (GAD-10), Activity level, Profile of Mood States (POMS) and Brief symptom Inventory-53 item (BSI-53) in remitters and non-responders.
Measured: At baseline and repeated across the study period to last follow-up after 12 weeks of antidepressant treatment.
Total daily cortisol output
Area under curve of 8 serial measures of salivary cortisol concentrations during an assessment day
Measured: Baseline (before treatment)
Changes in total daily cortisol output
Difference in area under curve of 8 serial measures of salivary cortisol concentrations during an assessment day
Measured: Baseline (before treatment) to 8 weeks of antidepressant treatment
Parental bonding quality
Self-reported parental bonding quality as assessed in baseline by parental bonding interview (PBI)
Measured: Baseline
5-HTTLPR genotype status
5-HTTLPR genotype status (binary), i.e. high-expressing LALA vs low-expressing (S or LG) variants
Measured: Baseline
Epigenetic FK506-binding protein 51 (FKBP5) status at baseline
Methylation of the FKBP5 gene
Measured: Baseline
Changes in epigenetic FKBP5 status from baseline
Changes in methylation status of the FKBP5 gene
Measured: Baseline to 8 and 12 weeks of intervention
Epigenetic 5-HTTLPR status at baseline
Methylation status of the 5-HTTLPR gene
Measured: Baseline
Changes in epigenetic 5-HTTLPR status from baseline
Changes in methylation status of the 5-HTTLPR gene
Measured: Baseline to 8 and 12 weeks of intervention
Epigenetic spindle and kinetochore associated complex subunit 2 (SKA2) status at baseline
Methylation status of the SKA2 gene
Measured: Baseline to 8 and 12 weeks of intervention
Changes in epigenetic SKA2 status from baseline
Changes in methylation status of the SKA2 gene
Measured: Baseline to 8 and 12 weeks of intervention
Performance on Face and Eyes Emotion Recognition Task
Differences between healthy controls and depressed patients at baseline and week 12 follow-up, as well as longitudinal alterations to treatment response in MDD patients.
Measured: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Performance on Intensity Morphing Task
Differences between healthy controls and depressed patients at baseline and week 12 follow-up, as well as longitudinal alterations to treatment response in MDD patients.
Measured: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Performance on Social Information Preference Task
Differences between healthy controls and depressed patients at baseline and week 12 follow-up, as well as longitudinal alterations to treatment response in MDD patients.
Measured: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Performance on Simple Reaction Time.
Differences between healthy controls and depressed patients at baseline and week 12 follow-up, as well as longitudinal alterations to treatment response in MDD patients.
Measured: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2016 (estimated)
- Study startAug 2016
- Primary completionJul 2019
- Study completionJul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Integrated Molecular Brain Imaging, Copenhagen, Denmak, Psychiatric Centre Copenhagen, Central Visitation, Region Hovedstaden
- Responsible party
- Principal investigator, Gitte Moos Knudsen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Gitte M Knudsen, MD,Prof., Principal investigator, Neurobiology Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02869035
- Sponsor's protocol ID
- NP1
- Status last verified
- Oct 2019
- First submitted
- 29 Jul 2016
- Last updated
- 16 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Via database of Center for Integrated Molecular Brain Imaging (Knudsen et al 2016, NeuroImage) data will be available for neuroscience research community contingent on approval by scientific board.
Publications
Ostergaard SD, Bech P, Miskowiak KW. Fewer study participants needed to demonstrate superior antidepressant efficacy when using the Hamilton melancholia subscale (HAM-D(6)) as outcome measure. J Affect Disord. 2016 Jan 15;190:842-845. doi: 10.1016/j.jad.2014.10.047. Epub 2014 Nov 7.
PubMed 25487682Jensen KHR, Aarestrup MR, Larsen SV, Kohler-Forsberg K, Knudsen GM, Jorgensen MB, Frokjaer VG. Psychoneuroendocrine profiles of unmedicated men with major depressive disorder and associations to treatment effects and sexual side-effects. Neurosci Appl. 2024 Feb 23;3:104050. doi: 10.1016/j.nsa.2024.104050. eCollection 2024.
PubMed 40656082Sankar A, Ozenne B, Dam VH, Svarer C, Jorgensen MB, Miskowiak KW, Frokjaer VG, Knudsen GM, Fisher PM. Association between brain serotonin 4 receptor binding and reactivity to emotional faces in depressed and healthy individuals. Transl Psychiatry. 2023 May 11;13(1):165. doi: 10.1038/s41398-023-02440-3.
PubMed 37169780Ip CT, Ganz M, Ozenne B, Olbrich S, Beliveau V, Dam VH, Kohler-Forsberg K, Jorgensen MB, Frokjaer VG, Knudsen GM. Association between the loudness dependence of auditory evoked potential, serotonergic neurotransmission and treatment outcome in patients with depression. Eur Neuropsychopharmacol. 2023 May;70:32-44. doi: 10.1016/j.euroneuro.2023.02.008. Epub 2023 Feb 28.
PubMed 36863106Weber S, Frokjaer VG, Armand S, Nielsen JH, Knudsen GM, Joergensen MB, Stenbaek DS, Giraldi A. Sexual function improves as depressive symptoms decrease during treatment with escitalopram: results of a naturalistic study of patients with major depressive disorder. J Sex Med. 2023 Feb 14;20(2):161-169. doi: 10.1093/jsxmed/qdac016.
PubMed 36763929Dam VH, Stenbaek DS, Kohler-Forsberg K, Cheng Ip, Ozenne B, Sahakian BJ, Knudsen GM, Jorgensen MB, Frokjaer VG. Evaluating cognitive disturbances as treatment target and predictor of antidepressant action in major depressive disorder: A NeuroPharm study. Transl Psychiatry. 2022 Nov 8;12(1):468. doi: 10.1038/s41398-022-02240-1.
PubMed 36347845Fisher PM, Ozenne B, Ganz M, Frokjaer VG, Dam VN, Penninx BW, Sankar A, Miskowiak K, Jensen PS, Knudsen GM, Jorgensen MB. Emotional faces processing in major depressive disorder and prediction of antidepressant treatment response: A NeuroPharm study. J Psychopharmacol. 2022 May;36(5):626-636. doi: 10.1177/02698811221089035. Epub 2022 May 13.
PubMed 35549538Ip CT, Olbrich S, Ganz M, Ozenne B, Kohler-Forsberg K, Dam VH, Beniczky S, Jorgensen MB, Frokjaer VG, Sogaard B, Christensen SR, Knudsen GM. Pretreatment qEEG biomarkers for predicting pharmacological treatment outcome in major depressive disorder: Independent validation from the NeuroPharm study. Eur Neuropsychopharmacol. 2021 Aug;49:101-112. doi: 10.1016/j.euroneuro.2021.03.024. Epub 2021 Apr 25.
PubMed 33910154Kohler-Forsberg K, Jorgensen A, Dam VH, Stenbaek DS, Fisher PM, Ip CT, Ganz M, Poulsen HE, Giraldi A, Ozenne B, Jorgensen MB, Knudsen GM, Frokjaer VG. Predicting Treatment Outcome in Major Depressive Disorder Using Serotonin 4 Receptor PET Brain Imaging, Functional MRI, Cognitive-, EEG-Based, and Peripheral Biomarkers: A NeuroPharm Open Label Clinical Trial Protocol. Front Psychiatry. 2020 Jul 23;11:641. doi: 10.3389/fpsyt.2020.00641. eCollection 2020.
PubMed 32792991
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predicting Treatment Outcome in Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT02869035
- Acronym / sponsor ID
- NP1
- Conditions
- Major Depressive Disorder
- Keywords
- PET, Serotonin, 5-HT4R, MRI, fMRI, EEG, Cortisol awakening response, Oxidative stress
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Center for Integrated Molecular Brain Imaging, Copenhagen, Denmak, Psychiatric Centre Copenhagen, Central Visitation, Region Hovedstaden
- Study start
- Aug 2016
- Primary completion
- Jul 2019 (actual)
- Study completion
- Jul 2019 (actual)
- First posted
- 16 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Major Depressive Disorder (MDD) is one of the most severe and frequently occurring brain disorders worldwide. It has been linked to serotonergic dysfunction, sexual dysfunction, vulnerability to stress and neuro-inflammation. However, at the same time the etiological understanding is limited. Most antidepressants act on the serotonin (5- HT) system, yet between 30-50 % of patients with MDD does not respond successfully to 5-HT acting drugs. Recent experimental models from our group suggest that cerebral 5-HT levels in vivo can be indexed through molecular brain imaging of the 5-HT 4 receptor (5-HT4R) with a novel Positron Emission Tomography (PET) ligand (11C-SB207145). Also, our human studies have confirmed that cerebral synaptic 5-HT is inversely related to 5-HT4R binding and this technique thus can be used to investigate the role of 5-HT tone in the brain in MDD with differential responses to standard antidepressant treatment. By using multimodal neuroimaging technology, we aim to determine the status of the 5-HT system prior to and after either successful or failed neuropharmacological intervention in a non-randomized longitudinal open clinical trial. 100 untreated patients with moderate to severe MDD will be included. Data collection from various neurobiological domains (i.e, 5-HT4R PET imaging, Magnetic Resonance Imaging (MRI), functional MRI (fMRI), electroencephalogram (EEG), psychometrics, neuropsychological tests, and peripheral biomarkers) will be conducted before, during and after 12 weeks of antidepressant treatment. The objective is to identify predictors of pharmacological antidepressant treatment response in depressed individuals before and after 8 weeks of antidepressant treatment.
Detailed description
Study population and study program:
Patients will be recruited through a unique new central referral site for "depression packages" in The Mental Health Services in the Capital Region of Denmark. 100 patients with MDD, 18-65 years of age, with moderate to severe single or recurrent episode of MDD (Hamilton 17 item (HAMD-17) score > 17) will be recruited through this portal. All diagnoses will be confirmed by a specialist in psychiatry.
Before initiation of pharmacological antidepressant treatment with escitalopram, patients will receive baseline examinations as follows: 1) 5-HT4R imaging with 11C-SB207145 PET-scan, 2) EEG examinations, 3) structural MRI, 4) functional MRI , 5) neuropsychological testing, 6) peripheral markers of immune-active cell responses, oxidative stress, cortisol-levels, RNA, genotypes and epigenetic factors will be measured in urine, saliva and peripheral blood at baseline and across the study period. Repeated measures across the study period include: 7) psychometrics by using self-reported questionnaires covering trait and state, including mental distress related to depression and other psychopathology, 8) neuropsychological examinations as well as 9) clinical follow-up with interview based ratings of mental status.
Patients will be treated with escitalopram at flexible doses of 10-20 mg/day adjusted depending on effects and side effects, and participate in clinical follow-up sessions at week 1, 2, 4 and 8. Patients with no response to escitalopram after 4 weeks will be shifted to a secondary pharmacological treatment (duloxetine). A final visit to determine longer-term clinical outcome will be performed at week 12. Compliance, side-effects to antidepressant treatment, and depressive symptoms will be monitored at each follow-up session.
The Hamilton 6 items (HAMD-6) subscale has recently shown to be more sensitive to antidepressant response (Østergaard et al), and will be used to identify treatment response in patients. Patients with > 50 % reduction in HAMD-6 after 4 weeks will be defined as early responders, and those with additional < 5 points on the HAMD-6 scale after 8 weeks will be considered in remission. Patients with >25% response at week 4 and < 50% reduction in HAMD-6 after full intervention will be considered non-responders. The assessment program including brain imaging with PET 11C-SB207145 will be conducted before drug intervention is initiated and, depending on treatment outcome, again after 8 weeks of antidepressant treatment in 20 patients in remission (remitters) and 20 non-responding patients (non-responders).
UPDATE: As per April 3, 2017 the rescanned group has been expanded to include various response patterns in order to capture rescan data from patients on a spectrum from poor to excellent treatment response, since out of the first 17 included patients only 1 patient fulfilled the non-responder criterion defined above. Accordingly, the clinical outcome parameter in the context will be changes in HAM-D6 from baseline at week 8.
Healthy controls:
From previous studies conducted at the Neurobiological Research Unit, there is access to brain imaging data and baseline PET-SB207145 brain images among healthy controls as well as an associated biobank with stored blood specimens. During the trial, additional healthy controls will be included and will receive baseline examinations and repeated neuropsychological testing after 12 weeks.
Hypotheses:
- 5-HT4R binding (as imaged by 11C-SB207145 PET) before treatment will predict antidepressant treatment outcome (remission vs non-response) in depressed patients; higher binding at baseline is hypothesized to be associated with a better treatment outcome. Likewise, secondary, 5-HT4R binding (as imaged by 11C-SB207145 PET) before treatment is expected to be associated with the magnitude of change from baseline in Hamilton score (HAMD-6) at 8 weeks.
- Remitters will display a greater reduction in 5-HT4R binding (as imaged by 11C-SB207145 PET) after antidepressant treatment relative to non-responders.
- Patients with MDD will have a higher 5-HT4R binding (as imaged by 11C-SB207145 PET) relative to healthy controls.
- High amygdala reactivity in an "emotional faces" fMRI paradigm before treatment predicts remission in response to antidepressant treatment.
- Amygdala response to exposure to negative emotional faces (fear and anger) and cerebral 5-HT4R binding is expected to be associated, both in cross-sectional comparison before treatment and with regard to longitudinal changes (changes from baseline).
- In resting state fMRI (rsfMRI), we expect that changes from baseline in a functional network centered around dorsomedial prefrontal cortex and other networks centered around anterior cingulate cortex and posterior cingulate cortex (default mode network) respectively will predict treatment outcome.
- Low activity in a brain network engaged in reward processing (as assessed by fMRI) will predict antidepressant treatment response (i.e. positive association between low activity and remitter- relative to non-responder group) both in cross-sectional comparison before treatment and with regard to longitudinal changes (changes from baseline).
- We expect reduced evoked gamma-activity measured with EEG and "Event-related-potentials" (ERP) in MDD patients compared to controls.
- Using EEG/ERP, we expect reduced alpha and theta cordance and higher theta band activity among remitters measured at baseline.
- Higher levels of systemic inflammation will predict poor cognitive function at baseline, and a poor antidepressant treatment outcome.
- A blunted cortisol awakening response (CAR) at baseline will predict a positive antidepressant treatment outcome.
- Restored HPA-axis dynamics (increased CAR compared to baseline) at week 8 will be associated with a positive treatment outcome.
- There will be a significant association between functional networks found by EEG and fMRI, both at baseline and as contrast between remitters and non-responders after 8 weeks.
- Hippocampal volume will predict treatment outcome.
- Patients with a low 5-HT4R binding (as imaged by 11C-SB207145 PET) at baseline before treatment will have a lower libido relative to patients with a high binding.
- Patients who respond to antidepressant treatment with the most pronounced changes in 5-HT4R binding (as imaged by 11C-SB207145) will experience a larger degree of sexual side-effects; i.e., the magnitude of 5-HT4R binding changes from baseline will be positively associated with the degree of sexual side-effects.
- Childhood abuse (defined by a composite measure of early life stress questionnaires) and anxious depression (defined as anxiety/somatization factor score in HAMD-17 > 7) predicts poor antidepressant treatment outcome.
- We expect urinary markers of oxidatively generated DNA/RNA damage to increase more in responders than in non-responders.
- With an exploratory approach it will be possible to identify a set of predictors of antidepressant treatment outcome. This explorative analysis includes genetics, epigenetics, peripheral and central neurobiological characteristics, neuropsychology testing outcomes, psychometry including self-reported mental distress, both cross-sectional at baseline and as longitudinal measures.
Ethical Aspects:
The study protocol complies with the Declaration of Helsinki II and approval by all relevant authorities will be obtained before initiation. All human volunteers will receive oral and written information about the given study and provide written informed consent before enrolment. The trial is monitored by a Good Clinical Practise unit for the relevant domains.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment of MDD patients | Experimental | Drug: EscitalopramTreatment of MDD patients with escitalopram |
| Healthy controls | No intervention | –No treatment. |
| Shift of treatment for MDD patients | Experimental | Drug: DuloxetineTreatment of MDD patients with duloxetine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Moderate to severe depression
- Age 18-65 years
- No previous antidepressant treatment the last 2 months
- Informed and signed consent
Key exclusion criteria (17 listed)
- More than one previous attempt with antidepressant drugs
- Duration of current depression more than 2 years
- Current or previous psychiatric severe co-morbidity
- Acute suicidal ideation
- Psychotic
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EscitalopramPatients will be treated with an antidepressant drug (escitalopram) at flexible standard doses for 12 weeks. If no response after 4 weeks; shift to duloxetine arm. | Drug | Treatment of MDD patients |
| DuloxetinePatients who at 4 weeks of escitalopram have not responded will be shifted to duloxetine at flexible standard dosages. | Drug | Shift of treatment for MDD patients |
Primary outcome
Binary treatment outcome in terms of remission from depression.
Time frame: Baseline to clinical follow-up at 8 weeks after antidepressant treatment.
Treatment outcome defined as changes in HAMD-6 score after antidepressant treatment (remitters and non-responders as previously defined).
Baseline cerebral 5-HT4R binding as imaged by 11C-SB207145 PET.
Time frame: Baseline.
Latent variable construct of 5-HT4R level based on quantification of 5-HT4R binding in primary volumes of interest; neocortex, nucleus caudatus, putamen and hippocampus. Assessed in depressed patients and healthy controls.
Changes from baseline in cerebral 5-HT4R binding as imaged by 11C-SB207145 PET
Time frame: Baseline to follow-up scan at 8 weeks after antidepressant treatment.
Difference in latent variable construct of 5-HT4R level based on quantification of 5-HT4R binding in primary volumes of interest; neocortex, nucleus caudatus, putamen and hippocampus. Measured in remitters and non-responders.
Baseline hippocampus volume
Time frame: Baseline.
Structural MRI scan in depressed patients and healthy controls.
Changes from baseline in hippocampus volume.
Time frame: Baseline to follow-up scan at 8 weeks after antidepressant treatment.
Structural MRI in remitters and non-responders.
Baseline fMRI BOLD response to an emotional faces paradigm
Time frame: Baseline
fMRI (BOLD response) based assessment of brain activity to emotionally salient, relative to neutral, stimuli.
Changes from baseline in fMRI BOLD response to an emotional faces paradigm
Time frame: Baseline to follow-up scan at 8 weeks after antidepressant treatment.
fMRI (BOLD response) based assessment of brain activity to emotionally salient, relative to neutral, stimuli.
Baseline fMRI BOLD response to reward paradigm.
Time frame: Baseline
fMRI (BOLD response) based assessment of brain activity in response to reward, relative to non-reward, stimuli.
Changes from baseline in fMRI BOLD response to reward paradigm
Time frame: Baseline to follow-up scan at 8 weeks after antidepressant treatment.
fMRI (BOLD response) based assessment of brain activity in response to reward, relative to non-reward, stimuli.
Baseline rsfMRI based spontaneous co-fluctuations in low frequency BOLD signal (functional connectivity)
Time frame: Baseline
Assessed with rsfMRI scan in the resting state, i.e. non-goal oriented spontaneous thought and awake.
Changes from baseline in rsfMRI spontaneous co-fluctuations in low frequency BOLD signal (functional connectivity)
Time frame: Baseline to follow-up scan at 8 weeks after antidepressant treatment.
Assessed with rsfMRI scan in the resting state, i.e. non-goal oriented spontaneous thought and awake.
Sexual function in depression
Time frame: Baseline
Assessed with scores of self reported sexual function questionnaires in depressed patients and healthy controls.
Changes in sexual function
Time frame: Baseline to clinical follow-up at 8 or 12 weeks after antidepressant treatment, and baseline to follow-up scan at 8 weeks after antidepressant treatment.
Questionnaire-based self-reported sexual function in remitters and non-responders
Baseline EEG including event related potentials (ERP)
Time frame: Baseline
Assessment of evoked gamma activity, alpha and theta cordance band activity in depressed patients and healthy controls.
Changes in EEG including event related potentials (ERP)
Time frame: Baseline to follow-up examination at 8 weeks after antidepressant treatment.
Assessment of evoked gamma activity, alpha and theta cordance band activity in remitters and non-responders.
Cortisol awakening response
Time frame: Baseline
Cortisol changes in response to awakening as measured in saliva from 0 to 60 minutes after awakening in depressed patients and healthy controls.
Changes in cortisol awakening response (HPA-axis dynamics)
Time frame: Baseline and follow-up examination at 8 weeks after antidepressant treatment.
Measured in remitters and non-responders.
Systemic inflammation peripheral blood hsCRP and immunoactive cytokines
Time frame: Baseline and follow-up examination at 8 weeks after antidepressant treatment.
Measured with peripheral blood markers in plasma by high-sensitivity (hs) methods.
Changes in systemic inflammation peripheral blood hsCRP and immunoactive cytokines
Time frame: Baseline and follow-up examination at 8 weeks after antidepressant treatment.
Measured with peripheral blood markers in plasma by high-sensitivity (hs) methods.
Systemic oxidative stress in terms of 8-oxodG and 8-oxoGuo in urine
Time frame: Baseline
8-oxodG and 8-oxoGuo measured with mass spectrometry in spot-urine and normalized to urinary creatinine, in depressed patients and healthy controls.
Changes in systemic oxidative stress in terms of 8-oxodG and 8-oxoGuo in urine
Time frame: Baseline and follow-up examinations at 8 weeks after antidepressant treatment.
8-oxodG and 8-oxoGuo measured with mass spectrometry in spot-urine and normalized to urinary creatinine, in remitters and non-responders.
Early life Stress
Time frame: Baseline
Self-reported early life stress with the Children Abuse and Trauma Scale (CATS) questionnaire.
Performance on Verbal Affective Memory Tasks (VAMT-26).
Time frame: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Differences between healthy controls and depressed patients at baseline and week 12 follow-up, as well as longitudinal alterations to treatment response in MDD patients.
Performance on Moral Judgement Task
Time frame: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Differences between healthy controls and depressed patients at baseline and week 12 follow-up, as well as longitudinal alterations to treatment response in MDD patients.
Performance on Letter-Number Sequence Task.
Time frame: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Differences between healthy controls and depressed patients at baseline and week 12 follow-up, as well as longitudinal alterations to treatment response in MDD patients.
21 secondary outcomes
Changes from baseline in HAMD-6 score
Time frame: Baseline to follow-up at 8 and 12 weeks
HAMD-6 score after 8 and 12 weeks of antidepressant treatment
Time frame: Week 8 and 12 of treatment period
Regional 5-HT4R binding
Time frame: Measured at baseline and after 8 weeks of antidepressant treatment.
Sexual side-effects from antidepressant treatment
Time frame: 8 weeks of antidepressant treatment
Baseline latent variable construct of self-reported mental state
Time frame: Baseline
Baseline self reported family history of mood disorders
Time frame: Baseline
Changes from baseline in self-reported mental state questionnaire-based latent variable construct
Time frame: At baseline and repeated across the study period to last follow-up after 12 weeks of antidepressant treatment.
Total daily cortisol output
Time frame: Baseline (before treatment)
Changes in total daily cortisol output
Time frame: Baseline (before treatment) to 8 weeks of antidepressant treatment
Parental bonding quality
Time frame: Baseline
5-HTTLPR genotype status
Time frame: Baseline
Epigenetic FK506-binding protein 51 (FKBP5) status at baseline
Time frame: Baseline
Changes in epigenetic FKBP5 status from baseline
Time frame: Baseline to 8 and 12 weeks of intervention
Epigenetic 5-HTTLPR status at baseline
Time frame: Baseline
Changes in epigenetic 5-HTTLPR status from baseline
Time frame: Baseline to 8 and 12 weeks of intervention
Epigenetic spindle and kinetochore associated complex subunit 2 (SKA2) status at baseline
Time frame: Baseline to 8 and 12 weeks of intervention
Changes in epigenetic SKA2 status from baseline
Time frame: Baseline to 8 and 12 weeks of intervention
Performance on Face and Eyes Emotion Recognition Task
Time frame: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Performance on Intensity Morphing Task
Time frame: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Performance on Social Information Preference Task
Time frame: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Performance on Simple Reaction Time.
Time frame: From baseline to follow-up after 12 weeks of treatment with antidepressant treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2019.
- Background: PubMed 25487682Ostergaard SD, Bech P, Miskowiak KW. Fewer study participants needed to demonstrate superior antidepressant efficacy when using the Hamilton melancholia subscale (HAM-D(6)) as outcome measure. J Affect Disord. 2016 Jan 15;190:842-845. doi: 10.1016/j.jad.2014.10.047. Epub 2014 Nov 7.
- Derived from this study: PubMed 40656082Jensen KHR, Aarestrup MR, Larsen SV, Kohler-Forsberg K, Knudsen GM, Jorgensen MB, Frokjaer VG. Psychoneuroendocrine profiles of unmedicated men with major depressive disorder and associations to treatment effects and sexual side-effects. Neurosci Appl. 2024 Feb 23;3:104050. doi: 10.1016/j.nsa.2024.104050. eCollection 2024.
- Derived from this study: PubMed 37169780Sankar A, Ozenne B, Dam VH, Svarer C, Jorgensen MB, Miskowiak KW, Frokjaer VG, Knudsen GM, Fisher PM. Association between brain serotonin 4 receptor binding and reactivity to emotional faces in depressed and healthy individuals. Transl Psychiatry. 2023 May 11;13(1):165. doi: 10.1038/s41398-023-02440-3.
- Derived from this study: PubMed 36863106Ip CT, Ganz M, Ozenne B, Olbrich S, Beliveau V, Dam VH, Kohler-Forsberg K, Jorgensen MB, Frokjaer VG, Knudsen GM. Association between the loudness dependence of auditory evoked potential, serotonergic neurotransmission and treatment outcome in patients with depression. Eur Neuropsychopharmacol. 2023 May;70:32-44. doi: 10.1016/j.euroneuro.2023.02.008. Epub 2023 Feb 28.
- Derived from this study: PubMed 36763929Weber S, Frokjaer VG, Armand S, Nielsen JH, Knudsen GM, Joergensen MB, Stenbaek DS, Giraldi A. Sexual function improves as depressive symptoms decrease during treatment with escitalopram: results of a naturalistic study of patients with major depressive disorder. J Sex Med. 2023 Feb 14;20(2):161-169. doi: 10.1093/jsxmed/qdac016.
- Derived from this study: PubMed 36347845Dam VH, Stenbaek DS, Kohler-Forsberg K, Cheng Ip, Ozenne B, Sahakian BJ, Knudsen GM, Jorgensen MB, Frokjaer VG. Evaluating cognitive disturbances as treatment target and predictor of antidepressant action in major depressive disorder: A NeuroPharm study. Transl Psychiatry. 2022 Nov 8;12(1):468. doi: 10.1038/s41398-022-02240-1.
- Derived from this study: PubMed 35549538Fisher PM, Ozenne B, Ganz M, Frokjaer VG, Dam VN, Penninx BW, Sankar A, Miskowiak K, Jensen PS, Knudsen GM, Jorgensen MB. Emotional faces processing in major depressive disorder and prediction of antidepressant treatment response: A NeuroPharm study. J Psychopharmacol. 2022 May;36(5):626-636. doi: 10.1177/02698811221089035. Epub 2022 May 13.
- Derived from this study: PubMed 33910154Ip CT, Olbrich S, Ganz M, Ozenne B, Kohler-Forsberg K, Dam VH, Beniczky S, Jorgensen MB, Frokjaer VG, Sogaard B, Christensen SR, Knudsen GM. Pretreatment qEEG biomarkers for predicting pharmacological treatment outcome in major depressive disorder: Independent validation from the NeuroPharm study. Eur Neuropsychopharmacol. 2021 Aug;49:101-112. doi: 10.1016/j.euroneuro.2021.03.024. Epub 2021 Apr 25.
- Derived from this study: PubMed 32792991Kohler-Forsberg K, Jorgensen A, Dam VH, Stenbaek DS, Fisher PM, Ip CT, Ganz M, Poulsen HE, Giraldi A, Ozenne B, Jorgensen MB, Knudsen GM, Frokjaer VG. Predicting Treatment Outcome in Major Depressive Disorder Using Serotonin 4 Receptor PET Brain Imaging, Functional MRI, Cognitive-, EEG-Based, and Peripheral Biomarkers: A NeuroPharm Open Label Clinical Trial Protocol. Front Psychiatry. 2020 Jul 23;11:641. doi: 10.3389/fpsyt.2020.00641. eCollection 2020.
- Individual participant dataSharing planned: Yes. Via database of Center for Integrated Molecular Brain Imaging (Knudsen et al 2016, NeuroImage) data will be available for neuroscience research community contingent on approval by scientific board.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gitte M Knudsen, MD,Prof. principal investigator
Neurobiology Research Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Escitalopram and Duloxetine in people with Major Depressive Disorder, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Binary treatment outcome in terms of remission from depression. (time frame: Baseline to clinical follow-up at 8 weeks after antidepressant treatment.). The study lists 25 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02869035, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2019.