Peripheral Immunomarker Validation in Treatment-resistant Depression

NCT02752178 | Completed

• 1 other identifier: 15/EE/0092
• Study Type: observational
• Target: 393
• Locations: 1 country
• Sites: 5

Brief 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. 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).

Conditions

Depressive Disorder, Major

Keywords

Depression; Major depressive disorder; MDD

Outcome Measures

Primary Outcomes (2)

• C-reactive protein (CRP) levels (mg/l)

  One year after last participant visit

• Flow cytometric immunophenotype

  The exact antibody panel will be developed during the research study

  One year after last participant visit

Secondary Outcomes (4)

• Structural parameters of the brain

  One year after last participant visit

• Response to stimulus

  One year after last participant visit

• Microglial activation in the brain

  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

  One year after last participant visit

Study Arms (4)

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

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

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

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

Interventions

MA OTHER

Monoaminergic antidepressant use

DEP+MA+; DEP-MA+

DEP OTHER

Depression measured using the Hamilton Depression (HAM-D) questionnaire

DEP+MA+; DEP+MA-

Eligibility Criteria

• Age: 25 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

People with depression and healthy controls

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Cambridge: lead
• University of Oxford: collaborator
• University of Glasgow: collaborator
• University of Sussex: collaborator
• King's College London: collaborator
• Janssen, LP: collaborator
• H. Lundbeck A/S: collaborator
• GlaxoSmithKline: collaborator

Study Sites (5)

University of Sussex

Brighton, United Kingdom

Location

University of Cambridge

Cambridge, United Kingdom

Location

University of Glasgow

Glasgow, United Kingdom

Location

King's College London

London, United Kingdom

Location

University of Oxford

Oxford, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood and saliva samples will be stored in a linked anonymised form for immunophenotyping and DNA analysis

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

1-(2-(dodecyloxy)ethyl)pyrrolidine hydrochloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Edward T Bullmore, FRCPsych

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Edward T. Bullmore

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: April 26, 2016
• Study Start: June 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: September 25, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share

Locations

GB (5)