Clinical trial NCT02456948: Adjunct Minocyline in Treatment-resistant Depression
Official title: A Double-blind, Placebo-controlled, Randomized, Multicenter Proof-of-principle Trial of Adjunctive Minocycline for Patients With Unipolar Major Depressive Disorder (MDD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: treatment resistant depression
inflammation
microglia
minocycline
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2015-05-29
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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)

Primary outcomes:
measure: Response as per MADRS (Montgomery-Åsberg Depression Rating Scale)
timeFrame: 6 weeks
Secondary outcomes:
measure: Remission as per MADRS (Montgomery-Åsberg Depression Rating Scale)
timeFrame: 6 weeks
measure: HAM-D-17-Scale (17-item Hamilton Depression Rating Scale)
timeFrame: 6 weeks
measure: BDI-Scale (Beck Depression Inventory, Self Rating Scale)
timeFrame: 6 weeks
measure: CGI-Scale (Clinical Global Impressions Scale)
timeFrame: 6 weeks
measure: SCL-90-R (Symptom Checklist 90-R, Self Rating Scale)
timeFrame: 6 weeks
measure: Transcriptomic changes in patient-specific peripheral blood-derived monocytic cells
timeFrame: 6 weeks
measure: Protein levels of various inflammation-associated markers in patient sera
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Heidelberg University Hospital, Department of Psychiatry
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Department of Psychiatry, Universitiy Hospital
state: Bavaria
city: Munich
country: Germany
facility: Department of Psychiatry, LMU Munich
state: Bavaria
city: Munich
country: Germany
facility: Max Planck Institute of Psychiatry
state: Bavaria
city: Regensburg
country: Germany
facility: Department of Psychiatry, Universitiy Hospital
state: Bavaria
city: Göttingen
country: Germany
facility: Department of Psychiatry, University Medical Center Göttingen
state: Lower Saxony
city: Aachen
country: Germany
facility: Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital RWTH Aachen
city: Berlin
country: Germany
facility: Department of Psychiatry, Charité - Campus Benjamin Franklin
city: Frankfurt
country: Germany
facility: Dept. of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt
Study officials:
affiliation: Chair: Department of Psychiatry Charité - Campus Benjamn
name: Isabella Heuser, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: