ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02362529
Recruitment Status : Recruiting
First Posted : February 13, 2015
Last Update Posted : July 21, 2017
Sponsor:
Information provided by (Responsible Party):
Jeff Meyer, Centre for Addiction and Mental Health

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.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: Minocycline Drug: Placebo Drug: Celecoxib Early Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 115 participants
Allocation: Randomized
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Minocycline
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.
Drug: Placebo
Lactose monohydrate in identical gel capsules to minocycline, oral administration.
Other Name: Lactose monohydrate

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.
Drug: Celecoxib
100 mg and 200 mg capsules, oral administration.
Other Name: Celebrex (Pfizer)




Primary Outcome Measures :
  1. 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 .

  2. 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


Secondary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

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


Contacts
Contact: Jeffrey H Meyer, MD, PhD 4165358501 ext 34007 jeff.meyer@camhpet.ca

Locations
Canada, Ontario
Centre for Addiction and Mental Health Recruiting
Toronto, Ontario, Canada, M5T 1R8
Principal Investigator: Jeffrey H Meyer, MD, PhD         
Sponsors and Collaborators
Centre for Addiction and Mental Health
Investigators
Principal Investigator: Jeffrey H Meyer, MD, PhD Centre for Addiction and Mental Health; University of Toronto

Responsible Party: Jeff Meyer, Head Neurochemical Imaging in Mood Disorders, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT02362529     History of Changes
Other Study ID Numbers: REB056/2014
First Posted: February 13, 2015    Key Record Dates
Last Update Posted: July 21, 2017
Last Verified: July 2017

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Disease
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Celecoxib
Anti-Inflammatory Agents
Minocycline
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antirheumatic Agents
Anti-Bacterial Agents
Anti-Infective Agents