Depressive DisorderInflaDepNCT03314155
Cerebral Neuroinflammation During Major Depressive Episode
A study testing Cerebral neuroinflammation evaluation in people with Depressive Disorder, run by University Hospital, Toulouse at 4 sites in France.
Trial summary
the investigators make the following assumptions: 1) neuroinflammation in MDD can be measured by the [18 F ] DPA- 714 ; 2) it is accompanied by anatomical and functional changes in the frontal subcortical loops, strongly involved in MDD ; 3) neuroinflammation in patients might be a biomarker related to resistance to… Read more about this study
- Who is it for?
- Ages 25 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Depressive Disorder
- What is being tested?
- Cerebral neuroinflammation evaluation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 4 sitesFrance
- Study dates
- 7 Dec 2018to Jan 2024
- Phase
- Interventional
- 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 25 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written agreement for participation
- Able to understand instructions and information data
- Responding to MDD criteria (DSM-5)
- MADRS score> 20
- Antidepressant medication considered ineffective and before the introduction of a new treatment according to the recommendations (unchanged dosage for at least a week and plasma levels within the therapeutic range)
- Having met MDD criteria (DSM-5)
Show all 11Show fewer
- In remission for 8 weeks according to the DSM-5
- MADRS score <10
- Treated with antidepressants (unchanged dosage for at least week)
- Without any neurological or psychiatric previous disorder
- CRPus < 5mg/L
Who cannot join
- Patients without public insurance regime.
- Specific contraindication to the use of MRI (metallic material) or PET (specific allergy related to the ligand).
- Pregnant and breastfeeding women
- Persons deprived of liberty by judicial or administrative decision
- People hospitalized without consent, or subject to legal protection
- Persons unable to consent
Show all 15Show fewer
- Patients with a neurodegenerative disease, bipolar disease, chronic psychotic disorder, addictive disorder, Obsessive Compulsive Disorder, Post-Traumatic Stress disorder (PCL-S> ou =45), known system pathology
- Patients with a history of stroke
- Patients with an acute infectious disease
- Patients with chronic inflammatory pathology.
- Patients treated with anti-inflammatory and/or immunosuppressive, and/or antipsychotics, and/or diazepam
- No significant psychiatric or somatic history.
- No psychotropic treatment
- Suicidal risk (C-SSRS)
- Anxiety Disorders (MINI)
Trial locations and contacts
4 sites in 1 country.
France4 sites, 4 recruiting
- Not yet recruiting
CHU Bordeaux
Bordeaux, New Aquitaine, 33076
Bruno Aouizerate, PhD, 5 56 56 17 98 ext. 33, bruno.aouizerate@u-bordeaux.fr
Bruno Aouizerate, PhD
- Recruiting
CHRU Lapeyronie
Montpellier, Occitanie, 34295
Fanny Molière, PhD, 4 67 33 67 33 ext. 33, moliere@chu-montpellier.fr
Fanny Molière, PhD
- Recruiting
Hôpital de Psychiatrie
Toulouse, Midi-Pyrénées, 31059
Antoine Yrondi, PhD, 5 34 55 75 37 ext. 33, yrondi.a@chu-toulouse.fr
Antoine Yrondi, MD PhD
- Recruiting
Clinique Psychiatrique Universitaire CHRU Tours
Tours, Val-De-Loire, 37540
Wissam El-Hage, PhD, 2 47 47 80 43 ext. 33, wissam.elhage@univ-tours.fr
Wissam El-Hage, PhD
About this study
Official title: Cerebral Neuroinflammation During Major Depressive Episode: Multicentric Comparative Study.
the investigators make the following assumptions: 1) neuroinflammation in MDD can be measured by the [18 F ] DPA- 714 ; 2) it is accompanied by anatomical and functional changes in the frontal subcortical loops, strongly involved in MDD ; 3) neuroinflammation in patients might be a biomarker related to resistance to treatment in patients with MDD. If this assumptions are validated, then this study will enable a better understanding of the neuroinflammatory processes. This breakthrough could have a long term therapeutic impact, helping to target more specifically antidepressant drugs with anti-inflammatory action and / or drugs targeting neuroinflammation.
Read the detailed description
The most widespread pathophysiological hypothesis in major depressive disorder (MDD), is the hypothesis of monoamine deficit. The most used antidepressants in everyday clinical practice act by inhibiting the reuptake of monoamines. However, meta-analyzes evaluating the efficacy of antidepressants suggest that they are ineffective in 30 to 40% of patients. Inflammatory mechanisms might be related to the deficiency of monoamines, compromising the effectiveness of conventional antidepressants. Newly developed specific radiotracers allow the use of positron emission tomography (PET) imaging techniques to evaluate neuroinflammation. It has recently demonstrated the relevance of the [18F] DPA- 714 as a biomarker of neuroinflammation in humans in several neurological diseases.
- Conditions
- Depressive Disorder
- Being tested
- Cerebral neuroinflammation evaluation
- Keywords
- Depressive disorder, Treatment Resistant Depression, [18 F ] DPA- 714, PET, MRI, Inflammation
- Medical subject headings
- Depressive Disorder, Depressive Disorder, Treatment-Resistant, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cerebral neuroinflammation evaluationDiagnostic test
Pet scan following an injection of the radiotracer ([18F]DPA-714), to evaluate the neuroinflammation. MRI to evaluate functional and structural integrities. Blood test to analyze various inflammation marker (IL-6, Tumor Necrosis Factor (TNF) alpha, CRPus, and TSPO). And psychological scales to assess the depressive symptoms.
| Study group | Role | What they receive |
|---|---|---|
| Cerebral neuroinflammation evaluation | Experimental | The density of TSPO (which is an inflammation maker) is evaluated by the tracer's brain distribution volume ([18F] DPA-714). Receives: Diagnostic Test: Cerebral neuroinflammation evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
distribution pattern of neuroinflammation in Positron Emission Tomography (PET) data
Assessed between patients with MDD (experimental group), patients who have had a MDD and being in remission for at least 8 weeks, still treated with antidepressants, matched in age and gender with the experimental group (pathological control group) and control subjects, matched in gender and age with both patients' groups (control group).
Measured: Day 7
Secondary outcomes (4)
distribution pattern of neuroinflammation in PET data across all groups
Across all groups (i.e. experimental group, pathological control group and control group).
Measured: Day 7
patients with depressive symptoms and neuroinflammation (i.e. PET data).
Depressive symptoms are assessed by the Montgomery and Asberg Depression Scale (MADRS) and the Columbia-Suicide severity rating scale (CSSRS).
Correlation across all groups (experimental group, pathological control group and control group).
Measured: Day 7
patients with neuroinflammation (i.e. PET analysis) and MRI parameters for functional and structural integrities.
Correlation across all groups (experimental group, pathological control group and control group).
Measured: Day 7
patients with neuroinflammation (i.e. PET analysis) and biological markers of neuroinflammation (i.e. cytokines).
Correlation across all groups (experimental group, pathological control group and control group).
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2017
- Study start7 Dec 2018
- Primary completionJan 2024 (estimated)
- Study completionJan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antoine Yrondi, MD PhD, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03314155
- Sponsor's protocol ID
- RC31/16/8918
- Other IDs
- 2017-001478-40, 2017
- Acronym
- InflaDep
- Status last verified
- Mar 2023
- First submitted
- 21 Aug 2017
- Last updated
- 30 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sartorius N. The economic and social burden of depression. J Clin Psychiatry. 2001;62 Suppl 15:8-11.
PubMed 11444765Bakish D. New standard of depression treatment: remission and full recovery. J Clin Psychiatry. 2001;62 Suppl 26:5-9.
PubMed 11775091Papakostas GI, Petersen T, Mahal Y, Mischoulon D, Nierenberg AA, Fava M. Quality of life assessments in major depressive disorder: a review of the literature. Gen Hosp Psychiatry. 2004 Jan-Feb;26(1):13-7. doi: 10.1016/j.genhosppsych.2003.07.004.
PubMed 14757297Schildkraut JJ, Schanberg SM, Breese GR, Kopin IJ. Norepinephrine metabolism and drugs used in the affective disorders: a possible mechanism of action. Am J Psychiatry. 1967 Nov;124(5):600-8. doi: 10.1176/ajp.124.5.600. No abstract available.
PubMed 4383104Maes M, Noto C, Brietzke E. Omics-based depression and inflammation research. Braz J Psychiatry. 2015 Jan-Mar;37(1):1-2. doi: 10.1590/1516-4446-2015-3609. No abstract available.
PubMed 25806550Hasler G, van der Veen JW, Tumonis T, Meyers N, Shen J, Drevets WC. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 2007 Feb;64(2):193-200. doi: 10.1001/archpsyc.64.2.193.
PubMed 17283286Deschwanden A, Karolewicz B, Feyissa AM, Treyer V, Ametamey SM, Johayem A, Burger C, Auberson YP, Sovago J, Stockmeier CA, Buck A, Hasler G. Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C]ABP688 PET and postmortem study. Am J Psychiatry. 2011 Jul;168(7):727-34. doi: 10.1176/appi.ajp.2011.09111607. Epub 2011 Apr 15.
PubMed 21498461Entsuah AR, Huang H, Thase ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry. 2001 Nov;62(11):869-77. doi: 10.4088/jcp.v62n1106.
PubMed 11775046Blumberg HP, Kaufman J, Martin A, Whiteman R, Zhang JH, Gore JC, Charney DS, Krystal JH, Peterson BS. Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder. Arch Gen Psychiatry. 2003 Dec;60(12):1201-8. doi: 10.1001/archpsyc.60.12.1201.
PubMed 14662552Stone VE, Baron-Cohen S, Calder A, Keane J, Young A. Acquired theory of mind impairments in individuals with bilateral amygdala lesions. Neuropsychologia. 2003;41(2):209-20. doi: 10.1016/s0028-3932(02)00151-3.
PubMed 12459219Yrondi A, Aouizerate B, El-Hage W, Moliere F, Thalamas C, Delcourt N, Sporer M, Taib S, Schmitt L, Arlicot N, Meligne D, Sommet A, Salabert AS, Guillaume S, Courtet P, Galtier F, Mariano-Goulart D, Champfleur NM, Bars EL, Desmidt T, Lemaire M, Camus V, Santiago-Ribeiro MJ, Cottier JP, Fernandez P, Meyer M, Dousset V, Doumy O, Delhaye D, Capuron L, Leboyer M, Haffen E, Peran P, Payoux P, Arbus C. Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study). Front Psychiatry. 2018 Jul 24;9:326. doi: 10.3389/fpsyt.2018.00326. eCollection 2018.
PubMed 30087626
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cerebral Neuroinflammation During Major Depressive Episode: Multicentric Comparative Study.
- ClinicalTrials.gov ID
- NCT03314155
- Acronym / sponsor ID
- InflaDep / RC31/16/8918
- Conditions
- Depressive Disorder
- Keywords
- Depressive disorder, Treatment Resistant Depression, [18 F ] DPA- 714, PET, MRI, Inflammation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- 7 Dec 2018 (actual)
- Primary completion
- Jan 2024 (estimated)
- Study completion
- Jan 2024 (estimated)
- First posted
- 19 Oct 2017 (actual)
- 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.
the investigators make the following assumptions: 1) neuroinflammation in MDD can be measured by the [18 F ] DPA- 714 ; 2) it is accompanied by anatomical and functional changes in the frontal subcortical loops, strongly involved in MDD ; 3) neuroinflammation in patients might be a biomarker related to resistance to treatment in patients with MDD. If this assumptions are validated, then this study will enable a better understanding of the neuroinflammatory processes. This breakthrough could have a long term therapeutic impact, helping to target more specifically antidepressant drugs with anti-inflammatory action and / or drugs targeting neuroinflammation.
Detailed description
The most widespread pathophysiological hypothesis in major depressive disorder (MDD), is the hypothesis of monoamine deficit. The most used antidepressants in everyday clinical practice act by inhibiting the reuptake of monoamines. However, meta-analyzes evaluating the efficacy of antidepressants suggest that they are ineffective in 30 to 40% of patients. Inflammatory mechanisms might be related to the deficiency of monoamines, compromising the effectiveness of conventional antidepressants. Newly developed specific radiotracers allow the use of positron emission tomography (PET) imaging techniques to evaluate neuroinflammation. It has recently demonstrated the relevance of the [18F] DPA- 714 as a biomarker of neuroinflammation in humans in several neurological diseases.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cerebral neuroinflammation evaluation | Experimental | Diagnostic Test: Cerebral neuroinflammation evaluationThe density of TSPO (which is an inflammation maker) is evaluated by the tracer's brain distribution volume ([18F] DPA-714). |
Who may qualify
- Ages
- 25 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
Key exclusion criteria (15 listed)
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 |
|---|---|---|
| Cerebral neuroinflammation evaluationPet scan following an injection of the radiotracer ([18F]DPA-714), to evaluate the neuroinflammation. MRI to evaluate functional and structural integrities. Blood test to analyze various inflammation marker (IL-6, Tumor Necrosis Factor (TNF) alpha, CRPus, and TSPO). And psychological scales to assess the depressive symptoms. | Diagnostic test | Cerebral neuroinflammation evaluation |
Primary outcome
distribution pattern of neuroinflammation in Positron Emission Tomography (PET) data
Time frame: Day 7
Assessed between patients with MDD (experimental group), patients who have had a MDD and being in remission for at least 8 weeks, still treated with antidepressants, matched in age and gender with the experimental group (pathological control group) and control subjects, matched in gender and age with both patients' groups (control group).
4 secondary outcomes
distribution pattern of neuroinflammation in PET data across all groups
Time frame: Day 7
patients with depressive symptoms and neuroinflammation (i.e. PET data).
Time frame: Day 7
patients with neuroinflammation (i.e. PET analysis) and MRI parameters for functional and structural integrities.
Time frame: Day 7
patients with neuroinflammation (i.e. PET analysis) and biological markers of neuroinflammation (i.e. cytokines).
Time frame: Day 7
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2023.
- Background: PubMed 11444765Sartorius N. The economic and social burden of depression. J Clin Psychiatry. 2001;62 Suppl 15:8-11.
- Background: PubMed 11775091Bakish D. New standard of depression treatment: remission and full recovery. J Clin Psychiatry. 2001;62 Suppl 26:5-9.
- Background: PubMed 14757297Papakostas GI, Petersen T, Mahal Y, Mischoulon D, Nierenberg AA, Fava M. Quality of life assessments in major depressive disorder: a review of the literature. Gen Hosp Psychiatry. 2004 Jan-Feb;26(1):13-7. doi: 10.1016/j.genhosppsych.2003.07.004.
- Background: PubMed 4383104Schildkraut JJ, Schanberg SM, Breese GR, Kopin IJ. Norepinephrine metabolism and drugs used in the affective disorders: a possible mechanism of action. Am J Psychiatry. 1967 Nov;124(5):600-8. doi: 10.1176/ajp.124.5.600. No abstract available.
- Background: PubMed 25806550Maes M, Noto C, Brietzke E. Omics-based depression and inflammation research. Braz J Psychiatry. 2015 Jan-Mar;37(1):1-2. doi: 10.1590/1516-4446-2015-3609. No abstract available.
- Background: PubMed 17283286Hasler G, van der Veen JW, Tumonis T, Meyers N, Shen J, Drevets WC. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 2007 Feb;64(2):193-200. doi: 10.1001/archpsyc.64.2.193.
- Background: PubMed 21498461Deschwanden A, Karolewicz B, Feyissa AM, Treyer V, Ametamey SM, Johayem A, Burger C, Auberson YP, Sovago J, Stockmeier CA, Buck A, Hasler G. Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C]ABP688 PET and postmortem study. Am J Psychiatry. 2011 Jul;168(7):727-34. doi: 10.1176/appi.ajp.2011.09111607. Epub 2011 Apr 15.
- Background: PubMed 11775046Entsuah AR, Huang H, Thase ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry. 2001 Nov;62(11):869-77. doi: 10.4088/jcp.v62n1106.
- Background: PubMed 14662552Blumberg HP, Kaufman J, Martin A, Whiteman R, Zhang JH, Gore JC, Charney DS, Krystal JH, Peterson BS. Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder. Arch Gen Psychiatry. 2003 Dec;60(12):1201-8. doi: 10.1001/archpsyc.60.12.1201.
- Background: PubMed 12459219Stone VE, Baron-Cohen S, Calder A, Keane J, Young A. Acquired theory of mind impairments in individuals with bilateral amygdala lesions. Neuropsychologia. 2003;41(2):209-20. doi: 10.1016/s0028-3932(02)00151-3.
- Derived from this study: PubMed 30087626Yrondi A, Aouizerate B, El-Hage W, Moliere F, Thalamas C, Delcourt N, Sporer M, Taib S, Schmitt L, Arlicot N, Meligne D, Sommet A, Salabert AS, Guillaume S, Courtet P, Galtier F, Mariano-Goulart D, Champfleur NM, Bars EL, Desmidt T, Lemaire M, Camus V, Santiago-Ribeiro MJ, Cottier JP, Fernandez P, Meyer M, Dousset V, Doumy O, Delhaye D, Capuron L, Leboyer M, Haffen E, Peran P, Payoux P, Arbus C. Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study). Front Psychiatry. 2018 Jul 24;9:326. doi: 10.3389/fpsyt.2018.00326. eCollection 2018.
- Individual participant dataSharing planned: No
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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.
Antoine Yrondi, MD PhD principal investigator
University Hospital, Toulouse
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cerebral neuroinflammation evaluation in people with Depressive Disorder, run by University Hospital, Toulouse at 4 sites in France.
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 11 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 30 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Antoine Yrondi, MD PhD (5 34 55 75 37 ext. 33, yrondi.a@chu-toulouse.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
distribution pattern of neuroinflammation in Positron Emission Tomography (PET) data (time frame: Day 7). 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 NCT03314155, which also lists 11 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 30 Mar 2023.