Depressive Disorder, MajorBIODEPNCT02752178
Peripheral Immunomarker Validation in Treatment-resistant Depression
An observational study of Depressive Disorder, Major, run by University of Cambridge at 5 sites in United Kingdom.
Trial summary
This is a study to characterise the role of inflammatory processes in depression. There is compelling evidence that inflammation is often associated with, and can cause, depression. It is currently less clear that antiinflammatory drugs have meaningful antidepressant effect. Read more about this study
- Who is it for?
- Ages 25 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Depressive Disorder, Major
- What is being tested?
- MA and DEP
- How many people
- 393 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- Jun 2015to Sep 2018
- Phase
- Observational
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: People with depression and healthy controls
Who may be able to join
- Major depressive disorder diagnosed by structured clinical interview in accordance with Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria
- Aged 25-50 years inclusive
- HAM-D score at baseline
- DEP+MA+ subgroup > 13
- DEP+MA- subgroup > 17
- DEP-MA+ subgroup < 7
Show all 9Show fewer
- Able and willing to give informed consent, including consent to sharing of clinical information with the participant's general practitioner
- Willing to abstain from strenuous exercise for 72 hours prior to assessment
- Able to write, speak and understand English
Who cannot join
- Life time history of bipolar disorder or nonaffective psychosis
- Concurrent medication likely to compromise the interpretation of immunological data (including, but not limited to corticosteroids, or any other substance to be determined by the Principal Investigator or delegate)
- Pregnancy or breast feeding
- Active alcohol or drug abuse or dependence in the last 6 months
- Participation in clinical trial of an investigational drug within the last 12 months
- Lifetime history of any serious medical disorder likely to compromise the interpretation of immunological data (including, but not limited to, immunological disorders, cardiovascular disorders, malignancies or infection, or any other condition to be determined by the Principal Investigator or delegate)
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites
University of Sussex
Brighton
University of Cambridge
Cambridge
University of Glasgow
Glasgow
King's College London
London
University of Oxford
Oxford
About this study
Official title: A Clinical Biomarker Study of Immunological Phenotypes Associated With Monoaminergic Anti-depressant Response, and the Brain and Cognitive Phenotypes Associated With Variation in Peripheral C-reactive Protein (CRP) Levels, in Patients With Major Depressive Disorder (MDD).
This is a study to characterise the role of inflammatory processes in depression. There is compelling evidence that inflammation is often associated with, and can cause, depression. It is currently less clear that antiinflammatory drugs have meaningful antidepressant effect. One of the goals is to identify the subset of depressed patients that is most likely to respond better to an antiinflammatory drug than to a conventional antidepressant. The investigators will therefore undertake a study of patients with a diagnosis of major depressive disorder including four groups: i) incompletely responsive patients who have demonstrated failure to respond consistently or completely to standard treatment, ii) those who have responded well to treatment and are not currently depressed, iii) untreated patients who are currently depressed, iv) healthy volunteers with no history of depression. Participants will undergo a clinical assessment, an interview with a trained member of the research team and will complete self-rated questionnaires. Investigators will collect blood and saliva samples to measure certain immune markers. They will also perform magnetic resonance imaging (MRI) scans to look for MRI markers in the brain and investigate brain inflammation in a subsample of these patients using positron emission topography (PET) and cerebrospinal fluid (CSF) sampling (also called lumbar puncture).
Read the detailed description
The hypotheses are (i) that therapeutic resistance to monoaminergic (MA) antidepressant drugs is associated with peripheral biomarkers indicating abnormal activation of the innate immune system; and (ii) that peripheral inflammation, defined by blood levels of C-reactive protein (CRP), is associated with central nervous system inflammation and abnormal brain structure and function.
The objectives are to test these two hypotheses by collecting clinical, immunological and neuroimaging data on patients with depression (DEP+) recruited from a network of clinical research sites in the United Kingdom.
Primary objective:
To measure peripheral immunophenotypes in healthy volunteers (at least N=50) and 3 groups of depressed patients, categorised by their exposure and therapeutic response to monoaminergic antidepressants (up to N=200):
- Incompletely responsive patients (approximately N ~100) who are currently depressed after greater than 6 weeks of treatment with one or more monoaminergic antidepressants (DEP+MA+);
- Responsive patients (approximately N~50) who are not currently depressed after greater than 6 weeks of treatment with a monoaminergic antidepressant (DEP-MA+);
- Untreated patients (approximately N~50) who are currently depressed but have not been treated with monoaminergic antidepressants in the previous 6 weeks (DEP+MA-);
- Healthy volunteers (approximately N~50) who have no personal history of depression requiring treatment with either monoaminergic antidepressants or other clinical interventions including psychotherapy (DEP-MA-).
Secondary objective:
To measure brain and cognitive phenotypes in a subsample of up to N=100 depressed patients recruited, preferably from the primary cohort, on the basis of their CRP levels:
- Low CRP patients (N~45) will have CRP <= 3 mg/L
- High CRP patients (N~45) will have CRP > 3 mg/L
- Healthy volunteers (at least N=45).
All subjects in this sample will be assessed using structural and functional magnetic resonance imaging (MRI) and subjects providing additional specific consents will also be assessed using positron emission tomography (PET-MR), and/or lumbar puncture (LP) for cerebrospinal fluid (CSF) sampling.
- Conditions
- Depressive Disorder, Major
- Being tested
- MA, DEP
- Keywords
- Depression, Major depressive disorder, MDD
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MAOther
Monoaminergic antidepressant use
DEPOther
Depression measured using the Hamilton Depression (HAM-D) questionnaire
| Study group | Role | What they receive |
|---|---|---|
| DEP+MA+ | Incompletely responsive patients (approximately N ~100) who are currently depressed after greater than 6 weeks of treatment with one or more monoaminergic antidepressants Receives: Other: MA; Other: DEP | |
| DEP-MA+ | Responsive patients (approximately N~50) who are not currently depressed after greater than 6 weeks of treatment with a monoaminergic antidepressant Receives: Other: MA | |
| DEP+MA- | Untreated patients (approximately N~50) who are currently depressed but have not been treated with monoaminergic antidepressants in the previous 6 weeks Receives: Other: DEP | |
| DEP-MA- | Healthy volunteers (approximately N~50) who have no personal history of depression requiring treatment with either monoaminergic antidepressants or other clinical interventions including psychotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
C-reactive protein (CRP) levels (mg/l)
Measured: One year after last participant visit
Flow cytometric immunophenotype
The exact antibody panel will be developed during the research study
Measured: One year after last participant visit
Secondary outcomes (4)
Structural parameters of the brain
Measured using MRI. Specifically: larger grey matter volume loss, quantitative parameters (T1, T2), magnetization transfer, and the microstructure of grey and white matter
Measured: One year after last participant visit
Response to stimulus
Specifically: functional MRI (fMRI) signatures obtained in an emotional face recognition and a reward processing task, respectively.
Measured: One year after last participant visit
Microglial activation in the brain
Measured using Positron Emission Tomography (PET)
Measured: One year after last participant visit
Pro-inflammatory (M1-like) phenotype-producing cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α circulating in cerebrospinal fluid
Measured: One year after last participant visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2016 (estimated)
- Study startJun 2015
- Primary completionSep 2018
- Study completionSep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depressive Disorder, MajorStudies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 393 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford, University of Glasgow, University of Sussex, King's College London, Janssen, LP, H. Lundbeck A/S, GlaxoSmithKline
- Responsible party
- Principal investigator, Linda Pointon, University of Cambridge
- Investigators
- Edward T Bullmore, FRCPsych, Principal investigator, University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02752178
- Sponsor's protocol ID
- 15/EE/0092
- Acronym
- BIODEP
- Status last verified
- Sep 2018
- First submitted
- 16 Mar 2016
- Last updated
- 25 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: All publications resulting from this study will be made available Open Access. Additionally, supporting research data will be also made available. This page will be updated with information about research outputs as soon as they become available.
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Biomarker Study of Immunological Phenotypes Associated With Monoaminergic Anti-depressant Response, and the Brain and Cognitive Phenotypes Associated With Variation in Peripheral C-reactive Protein (CRP) Levels, in Patients With Major Depressive Disorder (MDD).
- ClinicalTrials.gov ID
- NCT02752178
- Acronym / sponsor ID
- BIODEP / 15/EE/0092
- Conditions
- Depressive Disorder, Major
- Keywords
- Depression, Major depressive disorder, MDD
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 393 participants (actual)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- University of Oxford, University of Glasgow, University of Sussex, King's College London, Janssen, LP, H. Lundbeck A/S, GlaxoSmithKline
- Study start
- Jun 2015
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 26 Apr 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.
This is a study to characterise the role of inflammatory processes in depression. There is compelling evidence that inflammation is often associated with, and can cause, depression. It is currently less clear that antiinflammatory drugs have meaningful antidepressant effect. One of the goals is to identify the subset of depressed patients that is most likely to respond better to an antiinflammatory drug than to a conventional antidepressant. The investigators will therefore undertake a study of patients with a diagnosis of major depressive disorder including four groups: i) incompletely responsive patients who have demonstrated failure to respond consistently or completely to standard treatment, ii) those who have responded well to treatment and are not currently depressed, iii) untreated patients who are currently depressed, iv) healthy volunteers with no history of depression. Participants will undergo a clinical assessment, an interview with a trained member of the research team and will complete self-rated questionnaires. Investigators will collect blood and saliva samples to measure certain immune markers. They will also perform magnetic resonance imaging (MRI) scans to look for MRI markers in the brain and investigate brain inflammation in a subsample of these patients using positron emission topography (PET) and cerebrospinal fluid (CSF) sampling (also called lumbar puncture).
Detailed description
The hypotheses are (i) that therapeutic resistance to monoaminergic (MA) antidepressant drugs is associated with peripheral biomarkers indicating abnormal activation of the innate immune system; and (ii) that peripheral inflammation, defined by blood levels of C-reactive protein (CRP), is associated with central nervous system inflammation and abnormal brain structure and function.
The objectives are to test these two hypotheses by collecting clinical, immunological and neuroimaging data on patients with depression (DEP+) recruited from a network of clinical research sites in the United Kingdom.
Primary objective:
To measure peripheral immunophenotypes in healthy volunteers (at least N=50) and 3 groups of depressed patients, categorised by their exposure and therapeutic response to monoaminergic antidepressants (up to N=200):
- Incompletely responsive patients (approximately N ~100) who are currently depressed after greater than 6 weeks of treatment with one or more monoaminergic antidepressants (DEP+MA+);
- Responsive patients (approximately N~50) who are not currently depressed after greater than 6 weeks of treatment with a monoaminergic antidepressant (DEP-MA+);
- Untreated patients (approximately N~50) who are currently depressed but have not been treated with monoaminergic antidepressants in the previous 6 weeks (DEP+MA-);
- Healthy volunteers (approximately N~50) who have no personal history of depression requiring treatment with either monoaminergic antidepressants or other clinical interventions including psychotherapy (DEP-MA-).
Secondary objective:
To measure brain and cognitive phenotypes in a subsample of up to N=100 depressed patients recruited, preferably from the primary cohort, on the basis of their CRP levels:
- Low CRP patients (N~45) will have CRP <= 3 mg/L
- High CRP patients (N~45) will have CRP > 3 mg/L
- Healthy volunteers (at least N=45).
All subjects in this sample will be assessed using structural and functional magnetic resonance imaging (MRI) and subjects providing additional specific consents will also be assessed using positron emission tomography (PET-MR), and/or lumbar puncture (LP) for cerebrospinal fluid (CSF) sampling.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| DEP+MA+ | – | Other: MA, Other: DEPIncompletely responsive patients (approximately N ~100) who are currently depressed after greater than 6 weeks of treatment with one or more monoaminergic antidepressants |
| DEP-MA+ | – | Other: MAResponsive patients (approximately N~50) who are not currently depressed after greater than 6 weeks of treatment with a monoaminergic antidepressant |
| DEP+MA- | – | Other: DEPUntreated patients (approximately N~50) who are currently depressed but have not been treated with monoaminergic antidepressants in the previous 6 weeks |
| DEP-MA- | – | –Healthy volunteers (approximately N~50) who have no personal history of depression requiring treatment with either monoaminergic antidepressants or other clinical interventions including psychotherapy |
Who may qualify
- Ages
- 25 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- People with depression and healthy controls
Key inclusion criteria (9 listed)
- Major depressive disorder diagnosed by structured clinical interview in accordance with Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria
- Aged 25-50 years inclusive
- HAM-D score at baseline
- Able and willing to give informed consent, including consent to sharing of clinical information with the participant's general practitioner
- Willing to abstain from strenuous exercise for 72 hours prior to assessment
Key exclusion criteria (6 listed)
- Life time history of bipolar disorder or nonaffective psychosis
- Concurrent medication likely to compromise the interpretation of immunological data (including, but not limited to corticosteroids, or any other substance to be determined by the Principal Investigator or delegate)
- Pregnancy or breast feeding
- Active alcohol or drug abuse or dependence in the last 6 months
- Participation in clinical trial of an investigational drug within the last 12 months
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 |
|---|---|---|
| MAMonoaminergic antidepressant use | Other | DEP+MA+, DEP-MA+ |
| DEPDepression measured using the Hamilton Depression (HAM-D) questionnaire | Other | DEP+MA+, DEP+MA- |
Primary outcome
C-reactive protein (CRP) levels (mg/l)
Time frame: One year after last participant visit
Flow cytometric immunophenotype
Time frame: One year after last participant visit
The exact antibody panel will be developed during the research study
4 secondary outcomes
Structural parameters of the brain
Time frame: One year after last participant visit
Response to stimulus
Time frame: One year after last participant visit
Microglial activation in the brain
Time frame: One year after last participant visit
Pro-inflammatory (M1-like) phenotype-producing cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α circulating in cerebrospinal fluid
Time frame: One year after last participant visit
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 25 Sep 2018.
- Individual participant dataSharing planned: Yes. All publications resulting from this study will be made available Open Access. Additionally, supporting research data will be also made available. This page will be updated with information about research outputs as soon as they become available.
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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.
Edward T Bullmore, FRCPsych principal investigator
University of Cambridge
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depressive Disorder, Major, run by University of Cambridge at 5 sites in United Kingdom.
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 9 inclusion and 6 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 25 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. 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?
C-reactive protein (CRP) levels (mg/l) (time frame: One year after last participant visit). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Sep 2018.