Adjunct Minocyline in Treatment-resistant Depression

Study Overview
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Brief Summary
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This study examines the antidepressant efficacy of minocycline as an adjunct to an antidepressant standard treatment (AD-ST), for patients with unipolar major depressive disorder (MDD).

Detailed Description
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This is a double-blind, placebo-controlled, randomized, multicenter proof-of-principle trial of adjunctive minocycline for patients with unipolar major depressive disorder (MDD). The study tests the antidepressant efficacy of minocycline as an adjunct to an antidepressant standard treatment (AD-ST), for patients with unipolar major depressive disorder (MDD). The respective AD, for which non-response has been documented, must be on a stable regimen for at least 14 days prior to inclusion. AD-ST will then be continued throughout the trial. Trial medication is adjunct oral minocycline 200 mg/day or placebo. Response to treatment will be measured via the Montgomery-Asberg Depression Rating Scale (MADRS). The total study duration for each patient will be 6 weeks.

Official Title
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A Double-blind, Placebo-controlled, Randomized, Multicenter Proof-of-principle Trial of Adjunctive Minocycline for Patients With Unipolar Major Depressive Disorder (MDD)

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Minocycline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent male or female between age 18 and 75 BMI between 18 and 40 inclusive Non-lactating, non-pregnant females of child-bearing potential must be willing to use an effective contraceptive method All participants must fulfil diagnostic criteria of moderate or severe MDD according to the DSM-5. HAMD-17 score of at least 16 points at baseline and a CGI-S score of at least 4. AD-ST must have been administered at a sufficient dose for at least 6 weeks in the current episode and at a stable regimen for at least 14 days prior to baseline. Dose and duration of AD-ST must be verifiable Exclusion Criteria: prevalence of neurodegenerative disorder prevalence of any neurological disorder that caused the depressive symptoms prevalence of any severe, unstable general medical condition, including chronic inflammatory disease such as rheumatoid arthritis or inflammatory bowel disease prevalence of any other psychiatric disorder that better explains the presence of depressive symptoms Improvement by more than 50% in HAMD-17 score during the last 14 days prior to baseline pregnant or nursing women will not be allowed. substance or alcohol abuse within past 6 months or positive urine drug screening abnormal thyroid function (euthyroid at presentation), liver or kidney dysfunction history of autoimmune disease (except Hashimotos thyroiditis) clinically significant laboratory abnormalities (outside normal ranges) current medication with anti-inflammatory substances (NSAIDs, corticosteroids)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minocycline<br>Minocycline and standard antidepressant treatment | Drug: Minocycline<br>* 6 weeks 200mg/day Minocycline add-on<br>* Other names: Minocin;|
| Placebo Comparator: Placebo<br>Placebo and standard antidepressant treatment | Drug: Placebo<br>* 6 weeks Placebo add-on<br>* Other names: Sugar pills, mimics Minocycline tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response as per MADRS (Montgomery-Åsberg Depression Rating Scale) |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission as per MADRS (Montgomery-Åsberg Depression Rating Scale) |  | 6 weeks | 
| HAM-D-17-Scale (17-item Hamilton Depression Rating Scale) |  | 6 weeks | 
| BDI-Scale (Beck Depression Inventory, Self Rating Scale) |  | 6 weeks | 
| CGI-Scale (Clinical Global Impressions Scale) |  | 6 weeks | 
| SCL-90-R (Symptom Checklist 90-R, Self Rating Scale) |  | 6 weeks | 
| Transcriptomic changes in patient-specific peripheral blood-derived monocytic cells |  | 6 weeks | 
| Protein levels of various inflammation-associated markers in patient sera |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treatment resistant depression, inflammation, microglia, minocycline