- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02752178
Peripheral Immunomarker Validation in Treatment-resistant Depression (BIODEP)
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).
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
Brighton, United Kingdom
- University of Sussex
-
Cambridge, United Kingdom
- University of Cambridge
-
Glasgow, United Kingdom
- University of Glasgow
-
London, United Kingdom
- King's College London
-
Oxford, United Kingdom
- University of Oxford
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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)
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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
|
Monoaminergic antidepressant use
Depression measured using the Hamilton Depression (HAM-D) questionnaire
|
DEP-MA+
Responsive patients (approximately N~50) who are not currently depressed after greater than 6 weeks of treatment with a monoaminergic antidepressant
|
Monoaminergic antidepressant use
|
DEP+MA-
Untreated patients (approximately N~50) who are currently depressed but have not been treated with monoaminergic antidepressants in the previous 6 weeks
|
Depression measured using the Hamilton Depression (HAM-D) questionnaire
|
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 the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
C-reactive protein (CRP) levels (mg/l)
Time Frame: One year after last participant visit
|
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
|
One year after last participant visit
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Structural parameters of the brain
Time Frame: One year after last participant visit
|
Measured using MRI.
Specifically: larger grey matter volume loss, quantitative parameters (T1, T2), magnetization transfer, and the microstructure of grey and white matter
|
One year after last participant visit
|
Response to stimulus
Time Frame: One year after last participant visit
|
Specifically: functional MRI (fMRI) signatures obtained in an emotional face recognition and a reward processing task, respectively.
|
One year after last participant visit
|
Microglial activation in the brain
Time Frame: One year after last participant visit
|
Measured using Positron Emission Tomography (PET)
|
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
|
One year after last participant visit
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Edward T Bullmore, FRCPsych, University of Cambridge
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 15/EE/0092
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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