A Pilot Study Investigating the Efficacy of Minocycline and N-Acetyl Cysteine for Bipolar Depression

NCT02719392 | Suspended Phase 4 DMC FDA Drug

• 1 other identifier: 2016P000447
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the Pilot Study Investigating the Efficacy of Minocycline and n-acetylcysteine for Bipolar Depression is to test the effectiveness of minocycline, n-acetylcysteine, and combined minocycline and n-acetylcysteine pharmacotherapy in order to fill the gap in treatments for bipolar depression. The treatment of bipolar depression remains the greatest unmet need in the management of this lifelong and chronic psychiatric disorder.

Conditions

Bipolar Disorder; Bipolar Depression

Outcome Measures

Primary Outcomes (1)

• Illness severity on the Clinical Global Impression Scale-Bipolar Version (CGI-BP)

  The CGI-BP is a modified version of the CGI designed specifically for use in assessing global illness severity and change in patients with bipolar disorder. We will use the overall severity subscale to determine outcome.

  8 weeks

Secondary Outcomes (4)

• Quality of life on the Quality of Life, Enjoyment, and Satisfaction Questionnaire (QLES-Q)

  8 weeks

• Life satisfaction on the Longitudinal Interval Follow-up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT)

  8 weeks

• Depression severity on the Montgomery-Asberg Depression Rating Scale (MADRS)

  8 weeks

• Mania severity on the Young Mania Rating Scale (YMRS)

  8 weeks

Study Arms (4)

Minocycline

ACTIVE COMPARATOR

Patients in the minocycline group will take 1 minocycline (100mg) and 2 NAC placebo capsules in the morning and 1 minocycline (100mg) and 2 NAC placebo capsules in the evening for a total of 6 capsules per day over the course of the study.

Drug: Minocycline; Other: Placebo

N-acetylcysteine

ACTIVE COMPARATOR

Patients in the NAC group will take 2 NAC (500mg) capsules and 1 minocycline placebo capsule in the morning and 2 NAC (500mg) capsules and 1 minocycline placebo capsule in the evening for a total of 6 capsules per day over the course of the study.

Dietary Supplement: N-acetylcysteine; Other: Placebo

Minocycline + N-acetylcysteine

ACTIVE COMPARATOR

Patients in the minocycline NAC combination group will take 2 NAC (500mg) and 1 minocycline (100mg) capsule in the morning and 2 NAC (500mg) and 1 minocycline (100mg) capsule in the evening for a total of 6 capsules per day over the course of the study.

Dietary Supplement: N-acetylcysteine; Drug: Minocycline

Placebo Control

PLACEBO COMPARATOR

Patients in the placebo control group will take 2 NAC placebo capsules and 1 minocycline placebo capsule in the morning and 2 NAC placebo capsules and 1 minocycline placebo capsule in the evening for a total of 6 capsules per day over the course of the study.

Other: Placebo

Interventions

N-acetylcysteine DIETARY_SUPPLEMENT

NAC is an FDA-approved mucolytic (a type of drug used to relieve respiratory difficulties) and is also used for the treatment of acetaminophen toxicity.

Minocycline + N-acetylcysteine; N-acetylcysteine

Minocycline DRUG

Minocycline is an FDA-approved antibiotic commonly used to treat bacterial infections.

Minocycline; Minocycline + N-acetylcysteine

Placebo OTHER

The placebo control is an inactive sugar pill that mimics the active comparators in appearance.

Minocycline; N-acetylcysteine; Placebo Control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to give written informed consent and follow study procedures
• Age \> or = 18 years and \< or = 65 years
• Meets Diagnostic and Statistical Manual of Mental Disorders V (DSM-V) criteria for Bipolar Disorder Type I, which is the primary focus of treatment
• Currently depressed, as defined by a Montgomery-Asberg Depression Rating Scale (MADRS) score of \> or = 18 at screen and baseline (randomization)
• Participants will remain on baseline mood stabilizer pharmacotherapy with lithium during the study. They will need to have been on lithium with stable therapeutic blood levels for at least two weeks prior to randomization and agree not to change medications during the study.
• Women of child bearing potential must agree to use adequate contraception (e.g. oral contraceptives, intrauterine device, double barrier methods), if sexually active. Depo Provera is acceptable if it is started 3 months prior to enrollment. If hormonal contraceptives are used, participants must also agree to use a backup method of birth control. They will also need to understand the risks of lithium and other study treatments to the fetus and infant.

You may not qualify if:

• Unwilling or unable to comply with study requirements
• Patients who are a serious suicide or homicide risk, or currently in crisis such that inpatient hospitalization or other crisis management should take priority
• DSM-V diagnosis of Bipolar Disorder not otherwise specified, cyclothymia, schizoaffective bipolar type
• Primary anxiety disorders (e.g. Panic disorder, generalized anxiety disorder, post-traumatic stress disorder) or patients where the anxiety disorder is the primary focus of treatment
• Any history of obsessive compulsive disorder (OCD) or OCD-spectrum disorders
• Clinical or laboratory evidence of hypothyroidism; if maintained on thyroid medication must be euthyroid for at least 1 month before Visit 1
• Subjects having failed two or more trials of somatic therapy (i.e. medications for bipolar depression or Food and Drug Administration-approved devices) during the current bipolar depressive episode
• Drug/alcohol abuse or dependence active within the past 3 months, or current substance use disorder that requires detoxification
• Pregnancy (as determined by urine pregnancy test)
• Suspected or known clinically unstable systemic medical disorder including epilepsy, untreated endocrine disease, unstable angina, recent ulcers or significant esophagitis
• Conditions which may be negatively affected by minocycline treatment, such as inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease)
• History of significant treatment non-adherence or situations where the subject is unlikely to adhere to treatment, in the opinion of the investigator
• Current use of minocycline or history of anaphylactic reaction or intolerance to minocycline or any component of the preparation
• Current use of greater than 500mg of NAC/day, 200ug of selenium/day or 500 IU of Vitamin E/day
• History of anaphylactic reaction or intolerance to NAC or any component of the preparation

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Acetylcysteine; Minocycline

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Andrew A Nierenberg, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Bipolar Clinic and Research Program

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 25, 2016
• Study Start: August 9, 2017
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)