Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder
Information source: Centre for Addiction and Mental Health
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Major Depressive Disorder
Intervention: Minocycline (Drug); Placebo (Drug); Celecoxib (Drug)
Phase: Phase 0
Status: Recruiting
Sponsored by: Centre for Addiction and Mental Health Official(s) and/or principal investigator(s): Jeffrey H Meyer, MD, PhD, Principal Investigator, Affiliation: Centre for Addiction and Mental Health; University of Toronto
Overall contact: Jeffrey H Meyer, MD, PhD, Phone: 4165358501, Ext: 34007, Email: jeff.meyer@camhpet.ca
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.
Clinical Details
Official title: Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder
Study design: Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
Primary outcome: Translocator total distribution volume (TSPO VT): Treatment Effect of Minocycline in MDE SubjectsTranslocator total distribution volume (TSPO VT): Difference between MDE and healthy subjects
Secondary outcome: Change in Hamilton Depression Rating Scale Score
Detailed description:
There will be three consecutive 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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
Locations and Contacts
Jeffrey H Meyer, MD, PhD, Phone: 4165358501, Ext: 34007, Email: jeff.meyer@camhpet.ca
Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada; Recruiting Jeffrey H Meyer, MD, PhD, Principal Investigator
Additional Information
Starting date: February 2015
Last updated: February 19, 2015
|