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

NCT02362529 | Completed Early Phase 1 DMC

• 1 other identifier: REB056/2014
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (2)

• 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 .

  Pre- and post-minocycline or placebo treatment= 8 weeks total between pretreatment and posttreatment scans

• 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

  Pre-treatment scan will take place up to 8 weeks from initial assessment

Secondary Outcomes (1)

• Change in Hamilton Depression Rating Scale Score

  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 Outcomes (5)

• Hopkins Verbal Learning Test-Revised

  Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)

• Brief Visuospatial Memory Test-Revised

  Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)

• Comprehensive Trails Making Test

  Pre- and post-minocycline or placebo treatment.

Study Arms (3)

Minocycline

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Celecoxib

OTHER

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

Interventions

Minocycline DRUG

50 mg and 100 mg capsule, oral administration

Also known as: Mylan-minocycline

Minocycline

Placebo DRUG

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

Also known as: Lactose monohydrate

Placebo

Celecoxib DRUG

100 mg and 200 mg capsules, oral administration.

Also known as: Celebrex (Pfizer)

Celecoxib

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Minocycline; Celecoxib

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jeffrey H Meyer, MD, PhD

  Centre for Addiction and Mental Health; University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head Neurochemical Imaging in Mood Disorders

Study Record Dates

• First Submitted: February 4, 2015
• First Posted: February 13, 2015
• Study Start: February 1, 2015
• Primary Completion: April 1, 2019
• Study Completion: April 1, 2019
• Last Updated: May 23, 2019

Record last verified: 2019-05

Locations

CA (1)