Adjunct Minocyline in Treatment-resistant Depression (Mino-TRD)

• ClinicalTrials.gov Identifier: NCT02456948
• Recruitment Status: Completed
• First Posted: May 29, 2015
• Last Update Posted: October 19, 2020
• Sponsor: Charite University, Berlin, Germany
• Information provided by (Responsible Party): Isabella Heuser, Charite University, Berlin, Germany

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: Minocycline; Drug: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 168 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo-controlled, Randomized, Multicenter Proof-of-principle Trial of Adjunctive Minocycline for Patients With Unipolar Major Depressive Disorder (MDD)
• Actual Study Start Date: January 2015
• Actual Primary Completion Date: August 7, 2020
• Actual Study Completion Date: August 7, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Minocycline; Minocycline and standard antidepressant treatment	Drug: Minocycline; 6 weeks 200mg/day Minocycline add-on; Other Names: Solodyn; Minocin
Placebo Comparator: Placebo; Placebo and standard antidepressant treatment	Drug: Placebo; 6 weeks Placebo add-on; Other Name: Sugar pills, mimics Minocycline tablet

Outcome Measures

Primary Outcome Measures :

1. Response as per MADRS (Montgomery-Åsberg Depression Rating Scale) [ Time Frame: 6 weeks ]

Secondary Outcome Measures :

1. Remission as per MADRS (Montgomery-Åsberg Depression Rating Scale) [ Time Frame: 6 weeks ]
2. HAM-D-17-Scale (17-item Hamilton Depression Rating Scale) [ Time Frame: 6 weeks ]
3. BDI-Scale (Beck Depression Inventory, Self Rating Scale) [ Time Frame: 6 weeks ]
4. CGI-Scale (Clinical Global Impressions Scale) [ Time Frame: 6 weeks ]
5. SCL-90-R (Symptom Checklist 90-R, Self Rating Scale) [ Time Frame: 6 weeks ]
6. Transcriptomic changes in patient-specific peripheral blood-derived monocytic cells [ Time Frame: 6 weeks ]
7. Protein levels of various inflammation-associated markers in patient sera [ Time Frame: 6 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

Germany

Heidelberg University Hospital, Department of Psychiatry

Heidelberg, Baden-Württemberg, Germany, 69115

Department of Psychiatry, Universitiy Hospital

Erlangen, Bavaria, Germany, 91054

Department of Psychiatry, LMU Munich

Munich, Bavaria, Germany, 80336

Max Planck Institute of Psychiatry

Munich, Bavaria, Germany, 80804

Department of Psychiatry, Universitiy Hospital

Regensburg, Bavaria, Germany, 93053

Department of Psychiatry, University Medical Center Göttingen

Göttingen, Lower Saxony, Germany, 37075

Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital RWTH Aachen

Aachen, Germany

Department of Psychiatry, Charité - Campus Benjamin Franklin

Berlin, Germany, 12203

Dept. of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt

Frankfurt, Germany

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

• Principal Investigator: Isabella Heuser, MD, PhD; Chair: Department of Psychiatry Charité - Campus Benjamn

More Information

• Responsible Party: Isabella Heuser, MD, PhD, Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT02456948
• Other Study ID Numbers: 01EE1401F
• First Posted: May 29, 2015
• Last Update Posted: October 19, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Isabella Heuser, Charite University, Berlin, Germany:

treatment resistant depression; inflammation; microglia; minocycline

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Mood Disorders; Mental Disorders; Behavioral Symptoms; Minocycline; Anti-Bacterial Agents; Anti-Infective Agents