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Minocycline as Adjunctive Treatment for Treatment Resistant Depression (MINDEP2)

Primary Purpose

Treatment Resistant Depression

Status
Recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Minocycline
Sponsored by
Centre for Addiction and Mental Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment Resistant Depression focused on measuring Treatment Resistant Depression, Minocycline, Neuroinflammation, Microglial Activation, Biomarker

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Outpatients, voluntary and capable to consent
  2. DSM-5 diagnosis of non-psychotic MDD, single or recurrent
  3. Baseline HRSD score > 14
  4. ATHF total score > 3
  5. Current adequate trial of one of the following standard antidepressants: Escitalopram, Citalopram, Sertraline, Venlafaxine, Duloxetine, Mirtazapine or Bupropion
  6. If female of childbearing potential, currently on a medically acceptable form of birth control

Exclusion Criteria:

  1. DSM-5 substance use disorder within past 3 months, moderate or severe
  2. DSM-5 diagnosis of psychotic disorder, bipolar disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) within last year, or borderline personality disorder (BPD)
  3. Major unstable medical illness
  4. Intolerance or contraindication to tetracyclines
  5. Pregnancy or intent to become pregnant during study period
  6. Concomitant treatment with anticoagulants, diuretics, retinoids, ergot alkaloids, antacids containing aluminium, calcium or magnesium, bismuth and zinc salts, or quinapril
  7. Abnormal readings in hematology, liver, or renal function tests

Sites / Locations

  • Centre for Addiction and Mental HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active

Placebo

Arm Description

Minocycline will start at an oral dose of 100mg daily and will be increased after one week to 100mg twice daily.

Placebo capsules will start at one capsule daily, and will be increased after one week to one capsule twice daily

Outcomes

Primary Outcome Measures

Depressive symptoms
Changes from baseline to week 12 on the 17-item Hamilton Rating Scale for Depression (HRSD-17).

Secondary Outcome Measures

Response rate
Reduction of 50% or more in HRSD score from baseline to week 12
Remission rate
Final HRSD score < 8
Anxiety symptoms
Changes from baseline to week 12 in Generalized Anxiety Disorder scale (GAD-7)
Self-reported perception of quality of life
Changes from baseline to week 12 in World Health Organization Quality of Life Short Version (WHOQOL-BREF)
Clinician-rated illness severity
Changes from baseline to week 12 in Clinical Global Impression scale (CGI)

Full Information

First Posted
May 9, 2019
Last Updated
April 24, 2023
Sponsor
Centre for Addiction and Mental Health
Collaborators
The Physicians' Services Incorporated Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT03947827
Brief Title
Minocycline as Adjunctive Treatment for Treatment Resistant Depression
Acronym
MINDEP2
Official Title
Minocycline as Adjunctive Treatment for Treatment Resistant Depression: a Double Blind, Placebo-controlled, Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2020 (Actual)
Primary Completion Date
January 30, 2024 (Anticipated)
Study Completion Date
January 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre for Addiction and Mental Health
Collaborators
The Physicians' Services Incorporated Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Major depressive disorder (MDD) is a leading cause of disability worldwide. Up to 50% of patients experience treatment resistant depression (TRD), which accounts for a vast majority of disease burden. Current medications for TRD have limited efficacy and can be associated with intolerable side effects. Therefore, there is a need for finding new treatment targets. Accumulating evidence suggests some patients with MDD including those with TRD, display brain inflammation. Thus, patients with TRD may benefit from medications that can reduce this inflammation. Minocycline is an antibiotic which can cross the blood-brain barrier and has effects on several systems implicated in depression. The principal investigator led the first pilot study of minocycline as an add-on treatment in TRD demonstrating that it led to a significant reduction in depressive symptoms compared to placebo and these findings require replication in a larger sample to confirm the efficacy and tolerability of this treatment approach. This study is a 12 week, double-blind, placebo-controlled trial of minocycline as add-on treatment for patients suffering from a major depressive episode who have failed to respond to antidepressant treatment, confirmed by the Structured Clinical Interview for DSM-5 (SCID-5) and the Antidepressant Treatment History Form (ATHF) at screening. After screening and randomization to the two parallel arms of the trial, 50 patients will receive minocycline added to treatment as usual (TAU) and 50 patients will receive placebo added to TAU. Clinical assessment will include the Hamilton Depression Rating Scale (HRSD-17), Clinical Global Impression scale (CGI), World Health Organization Quality of Life Short Form (WHOQOL-BREF), and Generalized Anxiety Disorder scale (GAD-7), administered at each study visit (baseline, week 2, 6, and 12). Side effects checklists will be undertaken at each visit. Minocycline will be started at 100 mg once daily and will be increased to 100 mg twice daily at two weeks. Secondary outcomes include inflammatory biomarkers measured at baseline, weeks 6 and 12. This trial will provide further evidence of minocycline's efficacy and acceptability as a treatment option for patients with TRD and provide insights into its mechanism of action.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Depression
Keywords
Treatment Resistant Depression, Minocycline, Neuroinflammation, Microglial Activation, Biomarker

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Patients, their families, referring clinicians, lab workers and research assistants carrying out assessments will be concealed from allocation. Once randomized, pharmacy at the Centre for Addiction and Mental Health (CAMH) will be informed by email and deliver medication to the patient. An independent study psychiatrist will manage any clinical concerns and will be blind to treatment allocation. To assess the integrity of blinding procedures, participants and independent raters will be asked to complete a conventional guess form asking whether they believe participants received Minocycline or placebo as a treatment after the final ratings have been completed.
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active
Arm Type
Active Comparator
Arm Description
Minocycline will start at an oral dose of 100mg daily and will be increased after one week to 100mg twice daily.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo capsules will start at one capsule daily, and will be increased after one week to one capsule twice daily
Intervention Type
Drug
Intervention Name(s)
Minocycline
Other Intervention Name(s)
Apo-Minocycline
Intervention Description
Participants will be randomized to receive either Minocycline or placebo added to standard oral antidepressants.
Primary Outcome Measure Information:
Title
Depressive symptoms
Description
Changes from baseline to week 12 on the 17-item Hamilton Rating Scale for Depression (HRSD-17).
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Response rate
Description
Reduction of 50% or more in HRSD score from baseline to week 12
Time Frame
12 weeks
Title
Remission rate
Description
Final HRSD score < 8
Time Frame
12 weeks
Title
Anxiety symptoms
Description
Changes from baseline to week 12 in Generalized Anxiety Disorder scale (GAD-7)
Time Frame
12 weeks
Title
Self-reported perception of quality of life
Description
Changes from baseline to week 12 in World Health Organization Quality of Life Short Version (WHOQOL-BREF)
Time Frame
12 weeks
Title
Clinician-rated illness severity
Description
Changes from baseline to week 12 in Clinical Global Impression scale (CGI)
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Outpatients Voluntary and competent to consent to treatment DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the SCID-5 Male or female aged between 18-80 Total score > 3 on ATHF Baseline HRSD-17 score > 14 Able to adhere to study schedule If female of childbearing potential, currently on a medically acceptable form of birth control (oral contraceptives, contraceptive injections, IUD, contraceptive patch, male partner sterilization, abstinence, or barrier methods plus spermicide) Currently taking one of the following standard antidepressants: Escitalopram, Citalopram, Sertraline, Venlafaxine, Duloxetine, Mirtazapine or Bupropion Been on same dose of all psychotropic medications for > 4 weeks prior to enrolment Exclusion Criteria: DSM-5 substance use disorder within past 3 months, moderate or severe, based on SCID-5 Concomitant major unstable medical illness Pregnancy or intent to become pregnant during study period DSM-5 diagnosis of psychotic disorder, bipolar disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) within last year DSM-5 diagnosis of borderline personality disorder (BPD) Possible or probable dementia Prior or current intolerance or contraindication to tetracyclines Abnormal readings in hematology, liver, or renal function tests Have Myasthenia Gravis Concomitant treatment with anticoagulants, diuretics, retinoids, ergot alkaloids, antacids containing aluminium/calcium/magnesium, bismuth and zinc salts, or quinapril
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mary (Lily) Kittur
Phone
416-535-8501
Ext
33758
Email
research.study@camh.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ishrat Husain, MBBS, MD(Res.)
Organizational Affiliation
CAMH
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Addiction and Mental Health
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6J 1H4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mary (Lily) Kittur
Phone
416-535-8501
Ext
33758
Email
research.study@camh.ca
First Name & Middle Initial & Last Name & Degree
Ishrat Husain, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32295565
Citation
Husain MI, Cullen C, Umer M, Carvalho AF, Kloiber S, Meyer JH, Ortiz A, Knyahnytska Y, Husain MO, Giddens J, Diniz BS, Wang W, Young AH, Mulsant BH, Daskalakis ZJ. Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2). BMC Psychiatry. 2020 Apr 15;20(1):173. doi: 10.1186/s12888-020-02553-9.
Results Reference
derived

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Minocycline as Adjunctive Treatment for Treatment Resistant Depression

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