Bipolar DisorderPhase 4NCT02719392

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

A Phase 4 study testing N-acetylcysteine and Minocycline in people with Bipolar Disorder and Bipolar Depression, run by Massachusetts General Hospital at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Bipolar Disorder, Bipolar Depression
What is being tested?: N-acetylcysteine and Minocycline
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 0 participants
Where: 1 siteUnited States
Study dates: 9 Aug 2017to 20 Jul 2026
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 19Show fewer

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
A primary clinical diagnosis of a personality disorder, or comorbid diagnosis of antisocial or borderline personality disorder
A history of C. difficile colitis
A history of tetracycline allergy
Liver enzymes above the upper limit of normal

Trial locations and contacts

1 site in 1 country.

United States1 site

Massachusetts General Hospital
Boston, Massachusetts, 02114

Other trials in United States

About this study

Read the detailed 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.

Conditions: Bipolar Disorder, Bipolar Depression
Being tested: N-acetylcysteine, Minocycline, Placebo
Medical subject headings: Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

N-acetylcysteineDietary 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.
MinocyclineDrug
Minocycline is an FDA-approved antibiotic commonly used to treat bacterial infections.
PlaceboOther
The placebo control is an inactive sugar pill that mimics the active comparators in appearance.

Study groups in NCT02719392
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 8 weeks

Secondary outcomes (4)

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).
Measured: 8 weeks
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.
Measured: 8 weeks
Depression severity on the Montgomery-Asberg Depression Rating Scale (MADRS)
Assesses the severity of depressive symptoms
Measured: 8 weeks
Mania severity on the Young Mania Rating Scale (YMRS)
Assesses the severity of mania and hypomania symptoms
Measured: 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Aug 201720 Jul 2026

First posted25 Mar 2016 (estimated)
Study start9 Aug 2017
Primary completion20 Jul 2026
Study completion20 Jul 2026

Why it stopped: Study did not receive funding and was never carried out.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Bipolar DisorderStudies of the same condition, open and under way.
More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02719392
Sponsor's protocol ID: 2016P000447
Status last verified: Jul 2026
First submitted: 16 Mar 2016
Last updated: 24 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Bipolar Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study Investigating the Efficacy of Minocycline and N-Acetyl Cysteine for Bipolar Depression
ClinicalTrials.gov ID: NCT02719392
Acronym / sponsor ID: 2016P000447
Conditions: Bipolar Disorder, Bipolar Depression
Phase: Phase 4
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Study did not receive funding and was never carried out.
Enrolment: 0 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Study start: 9 Aug 2017 (actual)
Primary completion: 20 Jul 2026 (actual)
Study completion: 20 Jul 2026 (actual)
First posted: 25 Mar 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Minocycline	Active comparator	Drug: Minocycline, Other: PlaceboPatients 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.
N-acetylcysteine	Active comparator	Dietary Supplement: N-acetylcysteine, Other: PlaceboPatients 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.
Minocycline + N-acetylcysteine	Active comparator	Dietary Supplement: N-acetylcysteine, Drug: MinocyclinePatients 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.
Placebo Control	Placebo comparator	Other: PlaceboPatients 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.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (19 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
N-acetylcysteineNAC is an FDA-approved mucolytic (a type of drug used to relieve respiratory difficulties) and is also used for the treatment of acetaminophen toxicity.	Dietary supplement	Minocycline + N-acetylcysteine, N-acetylcysteine
MinocyclineMinocycline is an FDA-approved antibiotic commonly used to treat bacterial infections.	Drug	Minocycline, Minocycline + N-acetylcysteine
PlaceboThe placebo control is an inactive sugar pill that mimics the active comparators in appearance.	Other	Minocycline, N-acetylcysteine, Placebo Control

Primary outcome

Illness severity on the Clinical Global Impression Scale-Bipolar Version (CGI-BP)
Time frame: 8 weeks
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.

4 secondary outcomes

Quality of life on the Quality of Life, Enjoyment, and Satisfaction Questionnaire (QLES-Q)
Time frame: 8 weeks
Life satisfaction on the Longitudinal Interval Follow-up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT)
Time frame: 8 weeks
Depression severity on the Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: 8 weeks
Mania severity on the Young Mania Rating Scale (YMRS)
Time frame: 8 weeks

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2026.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Andrew A Nierenberg, M.D. principal investigator

Massachusetts General Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing N-acetylcysteine and Minocycline in people with Bipolar Disorder and Bipolar Depression, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Illness severity on the Clinical Global Impression Scale-Bipolar Version (CGI-BP) (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02719392.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2026.