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

Bipolar Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02719392
• Other study ID #: 2016P000447
• Status: Suspended
• Phase: Phase 4
• Start date: August 9, 2017
• Est. completion date: April 2024

Study information

• Verified date: April 2022
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The investigators are doing this research study to find out if minocycline alone, N-acetyl cysteine (NAC) alone, or the combination of minocycline and NAC can help people with bipolar depression when added to lithium. The investigators also want to find out if minocycline, NAC, and the combination of minocycline and NAC are safe to take without causing too many side effects. While the U.S. Food and Drug Administration (FDA) has approved minocycline to treat infections and acne and has approved NAC as a mucolytic, the FDA has not approved minocycline, n-acetylcysteine, or the combination of minocycline and n-acetylcysteine to treat bipolar depression. This research study will compare minocycline, n-acetylcysteine, and the combination of n-acetylcysteine and minocycline to placebo. The placebo looks exactly like the other study drugs, but contains neither minocycline nor NAC. During this study participants may get a placebo instead of minocycline, n-acetylcysteine, or the combination of minocycline and n-acetylcysteine. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 40
• Est. completion date: April 2024
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Able to give written informed consent and follow study procedures

2. Age > or = 18 years and < or = 65 years

3. Meets Diagnostic and Statistical Manual of Mental Disorders V (DSM-V) criteria for Bipolar Disorder Type I, which is the primary focus of treatment

4. Currently depressed, as defined by a Montgomery-Asberg Depression Rating Scale (MADRS) score of > or = 18 at screen and baseline (randomization)

5. 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.

6. 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.

Exclusion Criteria:

1. Unwilling or unable to comply with study requirements

2. Patients who are a serious suicide or homicide risk, or currently in crisis such that inpatient hospitalization or other crisis management should take priority

3. DSM-V diagnosis of Bipolar Disorder not otherwise specified, cyclothymia, schizoaffective bipolar type

4. 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

5. Any history of obsessive compulsive disorder (OCD) or OCD-spectrum disorders

6. Clinical or laboratory evidence of hypothyroidism; if maintained on thyroid medication must be euthyroid for at least 1 month before Visit 1

7. 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

8. Drug/alcohol abuse or dependence active within the past 3 months, or current substance use disorder that requires detoxification

9. Pregnancy (as determined by urine pregnancy test)

10. Suspected or known clinically unstable systemic medical disorder including epilepsy, untreated endocrine disease, unstable angina, recent ulcers or significant esophagitis

11. Conditions which may be negatively affected by minocycline treatment, such as inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease)

12. History of significant treatment non-adherence or situations where the subject is unlikely to adhere to treatment, in the opinion of the investigator

13. Current use of minocycline or history of anaphylactic reaction or intolerance to minocycline or any component of the preparation

14. Current use of greater than 500mg of NAC/day, 200ug of selenium/day or 500 IU of Vitamin E/day

15. History of anaphylactic reaction or intolerance to NAC or any component of the preparation

16. A primary clinical diagnosis of a personality disorder, or comorbid diagnosis of antisocial or borderline personality disorder

17. A history of C. difficile colitis

18. A history of tetracycline allergy

19. Liver enzymes above the upper limit of normal

Related Conditions & MeSH terms

• Bipolar Depression
• Bipolar Disorder
• Depression
• Depressive Disorder

Intervention

Dietary Supplement:
• N-acetylcysteine
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.

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

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

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Quality of life on the Quality of Life, Enjoyment, and Satisfaction Questionnaire (QLES-Q)	Assesses subjective quality of life (i.e. physical health, subjective feelings, leisure activities and social relationships).	8 weeks
Secondary	Life satisfaction on the Longitudinal Interval Follow-up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT)	Assesses extent to which psychopathology has impacted current functioning in work, household chores, interpersonal relationships with partner, family, and friends, recreational activities, and life satisfaction.	8 weeks
Secondary	Depression severity on the Montgomery-Asberg Depression Rating Scale (MADRS)	Assesses the severity of depressive symptoms	8 weeks
Secondary	Mania severity on the Young Mania Rating Scale (YMRS)	Assesses the severity of mania and hypomania symptoms	8 weeks