MINDEP2: Minocycline as Adjunctive Treatment for Treatment Resistant Depression

Sponsor

Centre for Addiction and Mental Health (Other)

Overall Status

Recruiting

CT.gov ID

NCT03947827

Collaborator

The Physicians' Services Incorporated Foundation (Other)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Treatment Resistant Depression	Drug: Minocycline	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes 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.

Primary Purpose:

Treatment

Official Title:

Minocycline as Adjunctive Treatment for Treatment Resistant Depression: a Double Blind, Placebo-controlled, Randomized Trial

Actual Study Start Date :

Feb 1, 2020

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active Minocycline will start at an oral dose of 100mg daily and will be increased after one week to 100mg twice daily.	Drug: Minocycline Participants will be randomized to receive either Minocycline or placebo added to standard oral antidepressants. Other Names: Apo-Minocycline
Placebo Comparator: Placebo Placebo capsules will start at one capsule daily, and will be increased after one week to one capsule twice daily	Drug: Minocycline Participants will be randomized to receive either Minocycline or placebo added to standard oral antidepressants. Other Names: Apo-Minocycline

Arm

Intervention/Treatment

Active Comparator: Active

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

Drug: Minocycline

Participants will be randomized to receive either Minocycline or placebo added to standard oral antidepressants.

Other Names:

Apo-Minocycline

Placebo Comparator: Placebo

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

Drug: Minocycline

Participants will be randomized to receive either Minocycline or placebo added to standard oral antidepressants.

Other Names:

Apo-Minocycline

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

DSM-5 substance use disorder within past 3 months, moderate or severe
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)
Major unstable medical illness
Intolerance or contraindication to tetracyclines
Pregnancy or intent to become pregnant during study period
Concomitant treatment with anticoagulants, diuretics, retinoids, ergot alkaloids, antacids containing aluminium, calcium or magnesium, bismuth and zinc salts, or quinapril
Abnormal readings in hematology, liver, or renal function tests