Back to resultsBiomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder
Primary Purpose
Major Depressive Disorder
Status
Completed
Phase
Early Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Minocycline
Placebo
Celecoxib
Sponsored by
About this trial
This is an interventional basic science trial for Major Depressive Disorder
Eligibility Criteria
Group 1 - Current major depressive episode (MDE) secondary to MDD
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.
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
Inclusion criteria:
- 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:
- 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
Sites / Locations
- Centre for Addiction and Mental Health
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Other
Arm Label
Minocycline
Placebo
Celecoxib
Arm Description
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.
The number and appearance of the pills would be identical to those in the minocycline arm.
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.
Outcomes
Primary Outcome Measures
Translocator total distribution volume (TSPO VT): Treatment Effect of Minocycline in MDE Subjects
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
Compare baseline TSPO VT prior to treatment between MDE group and healthy group
Secondary Outcome Measures
Change in Hamilton Depression Rating Scale Score
Change in HDRS score following minocycline vs. placebo treatment. Change in HDRS score following celecoxib treatment.
Full Information
NCT ID
NCT02362529
First Posted
February 4, 2015
Last Updated
May 22, 2019
Sponsor
Centre for Addiction and Mental Health
1. Study Identification
Unique Protocol Identification Number
NCT02362529
Brief Title
Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder
Official Title
Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
February 2015 (undefined)
Primary Completion Date
April 2019 (Actual)
Study Completion Date
April 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre for Addiction and Mental Health
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
7. Study Design
Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
115 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Minocycline
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The number and appearance of the pills would be identical to those in the minocycline arm.
Arm Title
Celecoxib
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Minocycline
Other Intervention Name(s)
Mylan-minocycline
Intervention Description
50 mg and 100 mg capsule, oral administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Lactose monohydrate
Intervention Description
Lactose monohydrate in identical gel capsules to minocycline, oral administration.
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Other Intervention Name(s)
Celebrex (Pfizer)
Intervention Description
100 mg and 200 mg capsules, oral administration.
Primary Outcome Measure Information:
Title
Translocator total distribution volume (TSPO VT): Treatment Effect of Minocycline in MDE Subjects
Description
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 .
Time Frame
Pre- and post-minocycline or placebo treatment= 8 weeks total between pretreatment and posttreatment scans
Title
Translocator total distribution volume (TSPO VT): Difference between MDE and healthy subjects
Description
Compare baseline TSPO VT prior to treatment between MDE group and healthy group
Time Frame
Pre-treatment scan will take place up to 8 weeks from initial assessment
Secondary Outcome Measure Information:
Title
Change in Hamilton Depression Rating Scale Score
Description
Change in HDRS score following minocycline vs. placebo treatment. Change in HDRS score following celecoxib treatment.
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).
Other Pre-specified Outcome Measures:
Title
Hopkins Verbal Learning Test-Revised
Description
To assess verbal memory we will administer the Hopkins Verbal Learning Test-Revised to MDE participants before and after treatment.
Time Frame
Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)
Title
Brief Visuospatial Memory Test-Revised
Description
To assess visuospatial memory we will administer the Brief Visuospatial Memory Test-Revised to MDE participants before and after treatment.
Time Frame
Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)
Title
Comprehensive Trails Making Test
Description
To assess psychomotor speed and attention we will administer the Comprehensive Trails Making Test to MDE participants before and after treatment.
Time Frame
Pre- and post-minocycline or placebo treatment.
Title
Genetic sample
Description
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.
Time Frame
Phase 1-single sample
Title
Blood samples (serum and plasma)
Description
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.
Time Frame
Pre- and post-minocycline or placebo treatment (8 weeks between measures). Pre- and post-celecoxib treatment (8 weeks between measures).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Group 1 - Current major depressive episode (MDE) secondary to MDD
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.
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
Inclusion criteria:
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:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey H Meyer, MD, PhD
Organizational Affiliation
Centre for Addiction and Mental Health; University of Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Addiction and Mental Health
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 1R8
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder
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