Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder
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|ClinicalTrials.gov Identifier: NCT02362529|
Recruitment Status : Recruiting
First Posted : February 13, 2015
Last Update Posted : July 21, 2017
|Condition or disease||Intervention/treatment||Phase|
|Major Depressive Disorder||Drug: Minocycline Drug: Placebo Drug: Celecoxib||Early Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||115 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Primary Purpose:||Basic Science|
|Official Title:||Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder|
|Study Start Date :||February 2015|
|Estimated Primary Completion Date :||June 2019|
|Estimated Study Completion Date :||July 2019|
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.
50 mg and 100 mg capsule, oral administration
Other Name: Mylan-minocycline
Placebo Comparator: Placebo
The number and appearance of the pills would be identical to those in the minocycline arm.
Lactose monohydrate in identical gel capsules to minocycline, oral administration.
Other Name: Lactose monohydrate
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.
100 mg and 200 mg capsules, oral administration.
Other Name: Celebrex (Pfizer)
- Translocator total distribution volume (TSPO VT): Treatment Effect of Minocycline in MDE Subjects [ Time Frame: Pre- and post-minocycline or placebo treatment= 8 weeks total between pretreatment and posttreatment scans ]TSPO VT will be measured using [18F]FEPPA positron emission tomography brain scans. Eligible MDE participants will be randomized to either minocycline or placebo. Following 8 weeks of either minocycline or placebo treatment, MDE participants will have a second PET scan .
- Translocator total distribution volume (TSPO VT): Difference between MDE and healthy subjects [ Time Frame: Pre-treatment scan will take place up to 8 weeks from initial assessment ]Compare baseline TSPO VT prior to treatment between MDE group and healthy group
- Change in Hamilton Depression Rating Scale Score [ Time Frame: Pre- and post-minocycline treatment (8 weeks total between pre- and post-treatment). Pre- and post-celecoxib treatment (8 weeks total between pre- and post-treatment). ]Change in HDRS score following minocycline vs. placebo treatment. Change in HDRS score following celecoxib treatment.
- Hopkins Verbal Learning Test-Revised [ Time Frame: Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure) ]To assess verbal memory we will administer the Hopkins Verbal Learning Test-Revised to MDE participants before and after treatment.
- Brief Visuospatial Memory Test-Revised [ Time Frame: Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure) ]To assess visuospatial memory we will administer the Brief Visuospatial Memory Test-Revised to MDE participants before and after treatment.
- Comprehensive Trails Making Test [ Time Frame: Pre- and post-minocycline or placebo treatment. ]To assess psychomotor speed and attention we will administer the Comprehensive Trails Making Test to MDE participants before and after treatment.
- Genetic sample [ Time Frame: Phase 1-single sample ]The priority of the genetic sample is to analyze the alleles of polymorphism rs6971 which has an association with the affinity of most second generation TSPO ligands including [18F]FEPPA. The genetic sample will also be used to study sequences of genes that are believed to affect TSPO expression, inflammation, mood and conditions that may predispose to mood disorders.
- Blood samples (serum and plasma) [ Time Frame: Pre- and post-minocycline or placebo treatment (8 weeks between measures). Pre- and post-celecoxib treatment (8 weeks between measures). ]Analyses will include complete blood cell count (CBC), ESR, hepatic and renal function. Peripheral marker analyses will include proteins related to TSPO expression and inflammation. Plasma minocycline and celecoxib levels will be analyzed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02362529
|Contact: Jeffrey H Meyer, MD, PhD||4165358501 ext firstname.lastname@example.org|
|Centre for Addiction and Mental Health||Recruiting|
|Toronto, Ontario, Canada, M5T 1R8|
|Principal Investigator: Jeffrey H Meyer, MD, PhD|
|Principal Investigator:||Jeffrey H Meyer, MD, PhD||Centre for Addiction and Mental Health; University of Toronto|