Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder

NCT ID: NCT02362529

Last Updated: 2019-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2019-04-30

Brief Summary

The purpose of this study is to determine if translocator protein total distribution volume (TSPO VT) is elevated in major depressive disorder that is not responding to medication and if adding minocycline can affect TSPO VT. Many remain treatment resistant with common antidepressant treatments and the investigators think it may be due to poor targeting of brain pathologies.

Detailed Description

There will be three Phases in the study. Only MDE subjects will be invited to continue to Phase 2 and 3. Subjects will be invited to continue to the subsequent Phase given they meet entry criteria described below:

Phase 1: The investigators will evaluate whether TSPO is elevated in individuals during a current MDE compared to healthy controls. Eligible participants will receive one [18F]FEPPA PET scan and one MRI scan. Other measures will include urine sample, blood samples for genetic and peripheral biomarker analysis, a neurocognitive battery, mood scales and questionnaires.

Phase 2: Participants who have elevated TSPO VT in Phase 1 and are agreeable to receiving minocycline will be invited to participate in Phase 2. Based on our previous results participants will be considered candidates for Phase 2 if TSPO VT ≥ 10.5 (HAB) or ≥8.5 (MAB) in any of the primary regions of interest (prefrontal cortex, anterior cingulate cortex or insula). Eligible participants will be invited to participate in a randomized, double blind, placebo controlled trial, to receive either minocycline or placebo. After the eight weeks of treatment, participants will receive one [18F]FEPPA PET scan. Other measures will include urine samples, blood samples, mood scales and questionnaires.

Phase 3: If, after the initial eight week treatment period with either minocycline or placebo, any participant continues to have depressive symptoms (17-item Hamilton Depression Rating Scale score ≥ 8) they will be invited to participate in an eight week open label trial of celecoxib. Participants not eligible for Phase 2 may also be invited to participate in Phase 3 directly from Phase 1.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Minocycline

The dose of minocycline would be 50mg per day on week 1, 50mg bid on week 2 and 100mg bid weeks 3-8. For tapering, the dose will be reduced to 50mg bid for a week, and then stopped.

Group Type: EXPERIMENTAL

Minocycline

Intervention Type: DRUG

50 mg and 100 mg capsule, oral administration

Placebo

The number and appearance of the pills would be identical to those in the minocycline arm.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Lactose monohydrate in identical gel capsules to minocycline, oral administration.

Celecoxib

This will be an open label trial for those with Hamilton Depression Rating Scale score ≥ 8 following the minocycline v. placebo trial or those not eligible for Phase 2. Dose of celecoxib will be 100 mg bid for the first week and 200mg bid for weeks 2-8. For tapering, the dose of celecoxib will be reduced to 100mg bid for one week, and then stopped.

Group Type: OTHER

Celecoxib

Intervention Type: DRUG

100 mg and 200 mg capsules, oral administration.

Interventions

Minocycline

50 mg and 100 mg capsule, oral administration

Intervention Type: DRUG

Placebo

Lactose monohydrate in identical gel capsules to minocycline, oral administration.

Intervention Type: DRUG

Celecoxib

100 mg and 200 mg capsules, oral administration.

Intervention Type: DRUG

Other Intervention Names

Mylan-minocycline; Lactose monohydrate; Celebrex (Pfizer)

Eligibility Criteria

Inclusion Criteria

• good physical health with no active medical conditions
• non-cigarette smoking
• no past or current substance abuse or dependence
• negative urine pregnancy test at screening and scan days (for women)
• primary diagnosis of current major depressive episode (MDE) and major depressive disorder (MDD) verified by SCID for DSM IV
• score greater than 19 on the 17 item HDRS
• non-response to a clinical trial of at least one antidepressant given at appropriate clinical dose
• willing to take medication for the duration of the trial and has previously taken antidepressants for the duration of the trial
• presently taking an antidepressant at a standard clinical dose.

• score below 8 on the 17 item HDRS
• good physical health
• non-cigarette smoking
• negative urine pregnancy test at screening and scan days (for women)
• negative urine screen for drugs of abuse

Exclusion Criteria

• history of neurological illness or autoimmune disorders
• never taken a tricyclic antidepressant or an antidepressant that raises norepinephrine
• received treatment with electroconvulsive therapy or mechanical brain stimulation in the previous 6 months
• currently taking medication contraindicated or that may possibly interact with either minocycline or celecoxib
• known intolerance or allergy to minocycline, other tetracyclines, sulfonamides or NSAIDs
• taken diazepam or other benzodiazepine use within the past month, except for lorazepam and clonazepam
• use of anti-inflammatory drugs or tetracyclines lasting ≥1 week within the past month
• history of severe hepatic or renal insufficiency, asthma, allergies, gastrointestinal disease, ischemic heart disease, cerebrovascular disease or congestive heart failure
• lactose intolerance

Group 2 - Healthy Controls - Phase 1 (baseline scan) only

• past or current diagnosis of axis I or axis II disorder as determined by the SCID I and SCID II for DSM IV
• history of psychotropic medication use
• history of neurological illness or autoimmune disorder

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centre for Addiction and Mental Health

OTHER

Sponsor Role: lead

Responsible Party

Jeff Meyer

Head Neurochemical Imaging in Mood Disorders

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey H Meyer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for Addiction and Mental Health; University of Toronto

Locations

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

REB056/2014

Identifier Type: -

Identifier Source: org_study_id