Major Depressive EpisodeBio-COPENCT03752853
Stress Systems and Psychotherapy in Depression
A study testing internet-based intervention for mild to moderate depression in people with Major Depressive Episode, run by Freie Universität Berlin at 1 site in Germany.
Trial summary
Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis as well as maladaptive activation of the autonomic nervous system (ANS) are discussed as relevant factors in the development of a major depressive episode and as a correlate of its clinical manifestation. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Episode
- What is being tested?
- internet-based intervention for mild to moderate depression
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteGermany
- Study dates
- 20 Nov 2018to 6 Aug 2020
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Current major depressive episode (F32.0, F32.1, F33.0, F33.1)
- Agreement to participate in the study
- At least 18 years of age
Who cannot join
- Diagnosis of schizophrenia, schizotypal and delusional disorders (F20-F29)
- Acute suicidal patients
- Acute manic episode
- Substance related abuse or addiction
- Pregnancy or lactation
- Chronic somatic diseases
Show all 9Show fewer
- Severe somatic diseases (e.g., endocrinological, neurological, autoimmune diseases)
- Glucocorticoid medication intake during the last six months
- Concurrent psychotherapeutic treatment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Biological Correlates of an Internet-based Psychological Intervention for Depression
Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis as well as maladaptive activation of the autonomic nervous system (ANS) are discussed as relevant factors in the development of a major depressive episode and as a correlate of its clinical manifestation. Preliminary evidence suggests that the hypercortisolaemic pattern in a subgroup of depressed patients may predict non-responses to psychotherapeutic treatment. At the same time, it is conceivable that disorder-related alterations in HPA axis and ANS regulation change in response to effective treatment, such as cognitive behavioural therapy (CBT), and that those changes could parallel changes in depressive symptoms. Identifying such associations may shed light on biological and psychological mechanisms of action underlying successful treatment.
However, so far, no studies have investigated depressed patients with regard to dysregulation in both stress systems, HPA axis and ANS, before psychotherapeutic treatment, nor have changes in functioning of both systems been inspected in response to treatment. Moreover, a detailed investigation of depressive symptom trajectories over the course of treatment and its associations with changes in HPA axis and ANS regulation is lacking. It can be speculated that specific techniques of the treatment, e.g., typical CBT elements, such as behavioural activation or cognitive restructuring, might particularly be associated with changes in HPA axis and ANS regulation.
Read more
The main aims of this project are to investigate:
- whether diurnal salivary cortisol and alpha-amylase as well as hair cortisol concentrations change from pre- to post-intervention in treatment responders compared to non-responders;
- whether diurnal salivary cortisol and alpha-amylase concentrations change from pre- to mid-intervention and from mid- to post-intervention in treatment responders compared to non-responders;
- whether changes in diurnal salivary cortisol, alpha-amylase and hair cortisol concentrations are significantly correlated with changes in depressive symptoms;
- whether concentrations of diurnal salivary cortisol and alpha-amylase as well as hair cortisol at pre-treatment predict future treatment response (i.e., on a psychological level). On an exploratory level, it will be investigated:
- which elements of a CBT intervention for depression (behavioural activation vs. cognitive restructuring) are associated with changes in diurnal salivary cortisol and alpha-amylase concentrations.
It is hypothesised:
- that pre- to post-intervention decreases in diurnal salivary cortisol and alpha-amylase as well as hair cortisol concentrations will be more pronounced in responders compared to non-responders.
- that pre- to mid-intervention and mid- to post-intervention decreases in diurnal salivary cortisol and alpha-amylase will be more pronounced in responders compared to non-responders.
- that changes in depressive symptoms will significantly correlate with changes in diurnal cortisol and diurnal alpha-amylase as well as hair cortisol concentrations.
- that pre-intervention diurnal salivary cortisol and alpha-amylase as well as hair cortisol concentrations will be higher in future non-responders, compared to responders.
Read the detailed description
Recruitment:
Patients will be recruited from an ongoing project providing an internet-based cognitive behavioral intervention for patients suffering from mild to moderate depression.
Protocol:
In this study, a total of N=42 patients fulfilling criteria for a current major depressive episode will undergo a 6-week internet-based cognitive behavioural intervention which consists of seven consecutive modules. Diurnal (salivary) and hair cortisol as well as diurnal (salivary) alpha-amylase will be assessed immediately before and after treatment, and at mid-treatment (i.e., after four of seven modules). Saliva samples (six samples per day) will be collected over two consecutive days. One hair sample will be obtained at pre- and post-intervention assessments respectively.
- Conditions
- Major Depressive Episode
- Being tested
- internet-based intervention for mild to moderate depression
- Keywords
- major depressive episode, cortisol, alpha-amylase, psychotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
internet-based intervention for mild to moderate depressionBehavioural
The six-weeks, therapist-guided, internet-based intervention for depression includes expressive writing tasks and further consists of key elements of cognitive behavioral therapy (CBT) for depression. In seven consecutive modules, patients receive psychoeducation and instructions for weekly tasks, and an individualized feedback letter of their therapist after each module. The intervention is effective in reducing depressive symptoms (Zagorscak et al., 2018). In the current study, patients will be randomly assigned to two different conditions with varying orders of modules: 1. patients will receive two modules (module 3 and 4) of behavioral activation, followed by two modules (modules 5 and 6) of cognitive restructuring; 2. patients will receive two modules (module 3 and 4) of cognitive restructuring, followed by two modules (modules 5 and 6) of behavioral activation. All other modules (1, 2 and 7) will be identical across conditions.
| Study group | Role | What they receive |
|---|---|---|
| iCBT for depression - behavioral activation first (BAF) | Experimental | internet-based intervention for mild to moderate depression: patients receive behavioral activation first, followed by cognitive restructuring Receives: Behavioral: internet-based intervention for mild to moderate depression |
| iCBT for depression - cognitive restructuring first (CRF) | Experimental | internet-based intervention for mild to moderate depression: patients receive cognitive restructuring first, followed by behavioral activation Receives: Behavioral: internet-based intervention for mild to moderate depression |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in salivary cortisol concentration
Changes in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of salivary cortisol concentration (nmol/l), measured on two consecutive days, at mid-intervention and post-intervention in responders compared to non-responders to the psychological intervention (assessed by Patient Health Questionnaire (PHQ-9))
Measured: pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)
Differences in salivary cortisol concentration
Differences in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of cortisol concentration (nmol/l), measured on two consecutive days, at pre-intervention in responders compared to non-responders to the psychological intervention (assessed by PHQ-9)
Measured: pre-intervention
Changes in salivary alpha-amylase concentration
Changes in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of salivary alpha-amylase concentration (U/ml), measured on two consecutive days, at mid-intervention and post-intervention in responders compared to non-responders to the psychological intervention (assessed by Patient Health Questionnaire (PHQ-9))
Measured: pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)
Differences in salivary alpha-amylase concentration
Differences in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of salivary alpha-amylase concentration (U/ml), measured on two consecutive days, at pre-intervention in responders compared to non-responders to the psychological intervention (assessed by PHQ-9)
Measured: pre-intervention
Changes in hair cortisol concentration
Changes in hair cortisol concentrations (nmol/l) at post-intervention in responders compared to non-responders to the psychological intervention (assessed by Patient Health Questionnaire (PHQ-9))
Measured: pre-intervention, post-intervention (after an average of six weeks)
Differences in hair cortisol concentration
Differences in hair cortisol concentrations (nmol/l) at pre-intervention in responders compared to non-responders to the psychological intervention (assessed by PHQ-9)
Measured: pre-intervention
Secondary outcomes (3)
Sleep quality (self-report)
Changes in Pittsburgh Sleep Quality Index (PSQI); scale ranges from 0 to 21
Measured: pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)
Chronic stress (self-report)
Changes in Trier Inventory for the assessment of chronic stress - TICS (Trier Inventar zum chronischen Stress), scale ranges from 0 to 48
Measured: pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)
Cognitive biases (self-report)
Changes in Cognitive Styles Assessment (COSTA-21); scale ranges from 0 to 5 per item
Measured: pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2018
- Study start20 Nov 2018
- Primary completion6 Aug 2020
- Study completion6 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive EpisodeStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Freie Universität Berlin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Sarah Schumacher, Freie Universität Berlin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03752853
- Sponsor's protocol ID
- Stress_DEP
- Acronym
- Bio-COPE
- Status last verified
- Oct 2020
- First submitted
- 13 Nov 2018
- Last updated
- 23 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Zagorscak P, Heinrich M, Sommer D, Wagner B, Knaevelsrud C. Benefits of Individualized Feedback in Internet-Based Interventions for Depression: A Randomized Controlled Trial. Psychother Psychosom. 2018;87(1):32-45. doi: 10.1159/000481515. Epub 2018 Jan 6.
PubMed 29306945
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biological Correlates of an Internet-based Psychological Intervention for Depression
- ClinicalTrials.gov ID
- NCT03752853
- Acronym / sponsor ID
- Bio-COPE / Stress_DEP
- Conditions
- Major Depressive Episode
- Keywords
- major depressive episode, cortisol, alpha-amylase, psychotherapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Freie Universität BerlinUniversity, hospital or other
- Study start
- 20 Nov 2018 (actual)
- Primary completion
- 6 Aug 2020 (actual)
- Study completion
- 6 Aug 2020 (actual)
- First posted
- 26 Nov 2018 (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.
Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis as well as maladaptive activation of the autonomic nervous system (ANS) are discussed as relevant factors in the development of a major depressive episode and as a correlate of its clinical manifestation. Preliminary evidence suggests that the hypercortisolaemic pattern in a subgroup of depressed patients may predict non-responses to psychotherapeutic treatment. At the same time, it is conceivable that disorder-related alterations in HPA axis and ANS regulation change in response to effective treatment, such as cognitive behavioural therapy (CBT), and that those changes could parallel changes in depressive symptoms. Identifying such associations may shed light on biological and psychological mechanisms of action underlying successful treatment.
However, so far, no studies have investigated depressed patients with regard to dysregulation in both stress systems, HPA axis and ANS, before psychotherapeutic treatment, nor have changes in functioning of both systems been inspected in response to treatment. Moreover, a detailed investigation of depressive symptom trajectories over the course of treatment and its associations with changes in HPA axis and ANS regulation is lacking. It can be speculated that specific techniques of the treatment, e.g., typical CBT elements, such as behavioural activation or cognitive restructuring, might particularly be associated with changes in HPA axis and ANS regulation.
The main aims of this project are to investigate:
- whether diurnal salivary cortisol and alpha-amylase as well as hair cortisol concentrations change from pre- to post-intervention in treatment responders compared to non-responders;
- whether diurnal salivary cortisol and alpha-amylase concentrations change from pre- to mid-intervention and from mid- to post-intervention in treatment responders compared to non-responders;
- whether changes in diurnal salivary cortisol, alpha-amylase and hair cortisol concentrations are significantly correlated with changes in depressive symptoms;
- whether concentrations of diurnal salivary cortisol and alpha-amylase as well as hair cortisol at pre-treatment predict future treatment response (i.e., on a psychological level). On an exploratory level, it will be investigated:
- which elements of a CBT intervention for depression (behavioural activation vs. cognitive restructuring) are associated with changes in diurnal salivary cortisol and alpha-amylase concentrations.
It is hypothesised:
- that pre- to post-intervention decreases in diurnal salivary cortisol and alpha-amylase as well as hair cortisol concentrations will be more pronounced in responders compared to non-responders.
- that pre- to mid-intervention and mid- to post-intervention decreases in diurnal salivary cortisol and alpha-amylase will be more pronounced in responders compared to non-responders.
- that changes in depressive symptoms will significantly correlate with changes in diurnal cortisol and diurnal alpha-amylase as well as hair cortisol concentrations.
- that pre-intervention diurnal salivary cortisol and alpha-amylase as well as hair cortisol concentrations will be higher in future non-responders, compared to responders.
Detailed description
Recruitment:
Patients will be recruited from an ongoing project providing an internet-based cognitive behavioral intervention for patients suffering from mild to moderate depression.
Protocol:
In this study, a total of N=42 patients fulfilling criteria for a current major depressive episode will undergo a 6-week internet-based cognitive behavioural intervention which consists of seven consecutive modules. Diurnal (salivary) and hair cortisol as well as diurnal (salivary) alpha-amylase will be assessed immediately before and after treatment, and at mid-treatment (i.e., after four of seven modules). Saliva samples (six samples per day) will be collected over two consecutive days. One hair sample will be obtained at pre- and post-intervention assessments respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| iCBT for depression - behavioral activation first (BAF) | Experimental | Behavioral: internet-based intervention for mild to moderate depressioninternet-based intervention for mild to moderate depression: patients receive behavioral activation first, followed by cognitive restructuring |
| iCBT for depression - cognitive restructuring first (CRF) | Experimental | Behavioral: internet-based intervention for mild to moderate depressioninternet-based intervention for mild to moderate depression: patients receive cognitive restructuring first, followed by behavioral activation |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Current major depressive episode (F32.0, F32.1, F33.0, F33.1)
- Agreement to participate in the study
- At least 18 years of age
Key exclusion criteria (9 listed)
- Diagnosis of schizophrenia, schizotypal and delusional disorders (F20-F29)
- Acute suicidal patients
- Acute manic episode
- Substance related abuse or addiction
- Pregnancy or lactation
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 |
|---|---|---|
| internet-based intervention for mild to moderate depressionThe six-weeks, therapist-guided, internet-based intervention for depression includes expressive writing tasks and further consists of key elements of cognitive behavioral therapy (CBT) for depression. In seven consecutive modules, patients receive psychoeducation and instructions for weekly tasks, and an individualized feedback letter of their therapist after each module. The intervention is effective in reducing depressive symptoms (Zagorscak et al., 2018). In the current study, patients will be randomly assigned to two different conditions with varying orders of modules: 1. patients will receive two modules (module 3 and 4) of behavioral activation, followed by two modules (modules 5 and 6) of cognitive restructuring; 2. patients will receive two modules (module 3 and 4) of cognitive restructuring, followed by two modules (modules 5 and 6) of behavioral activation. All other modules (1, 2 and 7) will be identical across conditions. | Behavioural | iCBT for depression - behavioral activation first (BAF), iCBT for depression - cognitive restructuring first (CRF) |
Primary outcome
Changes in salivary cortisol concentration
Time frame: pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)
Changes in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of salivary cortisol concentration (nmol/l), measured on two consecutive days, at mid-intervention and post-intervention in responders compared to non-responders to the psychological intervention (assessed by Patient Health Questionnaire (PHQ-9))
Differences in salivary cortisol concentration
Time frame: pre-intervention
Differences in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of cortisol concentration (nmol/l), measured on two consecutive days, at pre-intervention in responders compared to non-responders to the psychological intervention (assessed by PHQ-9)
Changes in salivary alpha-amylase concentration
Time frame: pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)
Changes in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of salivary alpha-amylase concentration (U/ml), measured on two consecutive days, at mid-intervention and post-intervention in responders compared to non-responders to the psychological intervention (assessed by Patient Health Questionnaire (PHQ-9))
Differences in salivary alpha-amylase concentration
Time frame: pre-intervention
Differences in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of salivary alpha-amylase concentration (U/ml), measured on two consecutive days, at pre-intervention in responders compared to non-responders to the psychological intervention (assessed by PHQ-9)
Changes in hair cortisol concentration
Time frame: pre-intervention, post-intervention (after an average of six weeks)
Changes in hair cortisol concentrations (nmol/l) at post-intervention in responders compared to non-responders to the psychological intervention (assessed by Patient Health Questionnaire (PHQ-9))
Differences in hair cortisol concentration
Time frame: pre-intervention
Differences in hair cortisol concentrations (nmol/l) at pre-intervention in responders compared to non-responders to the psychological intervention (assessed by PHQ-9)
3 secondary outcomes
Sleep quality (self-report)
Time frame: pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)
Chronic stress (self-report)
Time frame: pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)
Cognitive biases (self-report)
Time frame: pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)
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 23 Oct 2020.
- Background: PubMed 29306945Zagorscak P, Heinrich M, Sommer D, Wagner B, Knaevelsrud C. Benefits of Individualized Feedback in Internet-Based Interventions for Depression: A Randomized Controlled Trial. Psychother Psychosom. 2018;87(1):32-45. doi: 10.1159/000481515. Epub 2018 Jan 6.
- Individual participant dataSharing planned: Undecided
Related trials for Major Depressive Episode
RecruitingPhase 2
A Study to Evaluate TNX-102 SL Monotherapy Versus Placebo in Participants With Major Depressive Disorder (MDD)
Major Depressive Episode (MDE), Major Depressive Disorder (MDD)
Enrolling by invitationObservational study
Digital Phenotypes for Predicting Depression_Validation
Major Depressive Disorder, Bipolar I Disorder
RecruitingObservational study
Sensation Seeking and TMS Response in TRD
MDD, Severe Depression
Not yet recruiting
Evaluation of the Acceptability, Feasibility and Exploration of the Efficacy of an Integrated Care Pathway CARIBOU
Major Depressive Disorder (MDD)
Recruiting
French Minds Cohort: a French Longitudinal and Multimodal Cohort of Patients With Major Mood Disorders, Psychotic Disorders, Autism Spectrum Disorders, and Healthy Controls
Schizophrenia / Schizoaffective Disorder, First Episode Psychosis (FEP)
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing internet-based intervention for mild to moderate depression in people with Major Depressive Episode, run by Freie Universität Berlin at 1 site in Germany.
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 3 inclusion and 9 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 23 Oct 2020. 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 Germany. 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?
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?
Changes in salivary cortisol concentration (time frame: pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)). The study lists 6 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 NCT03752853, which also lists 1 linked publication.
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 23 Oct 2020.