Minocycline as Adjunctive Treatment for Treatment Resistant Depression

Treatment Resistant Depression Clinical Trial

— MINDEP2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03947827
• Other study ID #: 135/2018
• Status: Recruiting
• Phase: Phase 3
• Start date: February 1, 2020
• Est. completion date: September 30, 2024

Study information

• Verified date: April 2024
• Source: Centre for Addiction and Mental Health
• Contact: Mary (Lily) Kittur
• Phone: 416-535-8501
• Email: research.study[@]camh.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Outpatients

2. Voluntary and competent to consent to treatment

3. DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the SCID-5

4. Male or female aged between 18-80

5. Total score > 3 on ATHF

6. Baseline HRSD-17 score > 14

7. Able to adhere to study schedule

8. 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)

9. Currently taking one of the following standard antidepressants: Escitalopram, Citalopram, Sertraline, Venlafaxine, Duloxetine, Mirtazapine or Bupropion

10. Been on same dose of all psychotropic medications for > 4 weeks prior to enrolment

Exclusion Criteria:

1. DSM-5 substance use disorder within past 3 months, moderate or severe, based on SCID-5

2. Concomitant major unstable medical illness

3. Pregnancy or intent to become pregnant during study period

4. DSM-5 diagnosis of psychotic disorder, bipolar disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) within last year

5. DSM-5 diagnosis of borderline personality disorder (BPD)

6. Possible or probable dementia

7. Prior or current intolerance or contraindication to tetracyclines

8. Abnormal readings in hematology, liver, or renal function tests

9. Have Myasthenia Gravis

10. Concomitant treatment with anticoagulants, diuretics, retinoids, ergot alkaloids, antacids containing aluminium/calcium/magnesium, bismuth and zinc salts, or quinapril

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Treatment Resistant Depression

Intervention

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

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health	The Physicians' Services Incorporated Foundation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Depressive symptoms	Changes from baseline to week 12 on the 17-item Hamilton Rating Scale for Depression (HRSD-17).	12 weeks
Secondary	Response rate	Reduction of 50% or more in HRSD score from baseline to week 12	12 weeks
Secondary	Remission rate	Final HRSD score < 8	12 weeks
Secondary	Anxiety symptoms	Changes from baseline to week 12 in Generalized Anxiety Disorder scale (GAD-7)	12 weeks
Secondary	Self-reported perception of quality of life	Changes from baseline to week 12 in World Health Organization Quality of Life Short Version (WHOQOL-BREF)	12 weeks
Secondary	Clinician-rated illness severity	Changes from baseline to week 12 in Clinical Global Impression scale (CGI)	12 weeks