Bezafibrate for bipolar depression

A Pan-PPAR Agonist Treatment for Bipolar Depression: A Proof of Concept Study

This trial will try adding bezafibrate to existing anti-manic medication to see if it helps adults with bipolar depression.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Massachusetts General Hospital (Academic / other)
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT02481245 on ClinicalTrials.gov

What this trial studies

This is a phase IIa, 8-week, open-label pilot trial enrolling 30 adults with bipolar I or II currently experiencing a major depressive episode. Participants will continue an adequate, stable dose of an FDA-approved anti-manic medication and receive bezafibrate as an add-on. Study measures include changes in depressive and manic symptoms, suicidal ideation, attention and verbal memory, treatment-emergent adverse events, and Framingham cardiovascular risk score. The trial excludes individuals with current mania/hypomania, recent substance use disorders, certain psychotic or other excluded DSM-IV diagnoses, and those outside the 18–65 age range.

Who should consider this trial

Good fit: Adults 18 to 65 with bipolar I or II in a major depressive episode (MADRS >18) who are on a stable, adequate dose of an FDA-approved anti-manic medication and not currently manic or hypomanic are the intended participants.

Not a fit: People with current mania or hypomania, recent substance use, excluded psychotic diagnoses (e.g., schizophrenia, schizoaffective), bipolar NOS/cyclothymia, or those not on stable anti-manic treatment would not be eligible and are unlikely to benefit from this add-on approach.

Why it matters

Potential benefit: If successful, adding bezafibrate could reduce depressive symptoms in bipolar patients without triggering mania and might also impact cardiovascular risk factors.

How similar studies have performed: This is a relatively novel clinical application for bezafibrate with limited prior clinical data in bipolar depression, though PPAR agonists have shown some mood- and metabolism-related signals in preclinical work and small studies.

Eligibility criteria

Inclusion Criteria:

1. Men or women between the ages of 18 and 65 (inclusive)
2. DSM IV diagnosis of Bipolar Disorder Type I or Bipolar Disorder Type II
3. Ability to sign the Informed Consent Form
4. Taking an adequate dose of any FDA-approved anti-manic medication for at least two weeks prior to enrollment
5. Agrees not to change medications during the study
6. Meets criteria for a current major depressive episode as defined and operationalized by the MINI and by a MADRS score of \>18 at screen and baseline (randomization)
7. Does not meet criteria for current hypomanic or manic episode as defined and operationalized by the MINI

Exclusion Criteria:

1. The following DSM-IV diagnoses: (1) Bipolar NOS, (2) Cyclothymia, (3) Schizoaffective Disorder, (4) organic mental disorders, (5) substance use disorders, including alcohol, active within the 3 months, (6) schizophrenia, (7) delusional disorder, (8) psychotic disorders not elsewhere classified, (9) acute bereavement, (10) severe borderline or antisocial personality disorder, (11) OCD or OCD-spectrum disorders
2. Primary diagnosis of anxiety disorders or patients where the anxiety disorder is the primary focus of treatment
3. Patients with mood congruent or mood incongruent psychotic features
4. Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (e.g. oral contraceptives, intrauterine device, barrier methods, or total abstinence from intercourse; Depo Provera is acceptable if it is started 3 months prior to enrollment). Women who are nursing
5. Patients who are a serious suicide or homicide risk
6. Suspected or known clinically unstable systemic medical disorder including epilepsy, untreated endocrine disease, unstable angina, recent ulcers or significant esophagitis
7. Conditions which may be negatively affected by bezafibrate treatment, such as hepatobiliary disease
8. Clinical or laboratory evidence of hypothyroidism (if maintained on thyroid medication must be euthyroid for at least 1 month before Visit 1)
9. Subjects having failed two or more trials of somatic therapy (i.e., medications for bipolar depression or FDA-approved devices) during the current bipolar depressive episode
10. Current use of a fibrate or history of anaphylactic reaction or intolerance to fibrates or any component of the preparation
11. History of significant treatment non-adherence or situations where the subjects is unlikely to adhere to treatment, in the opinion of the investigator
12. History of stroke or cerebrovascular disease
13. Type 1 or Type II Diabetes requiring medication treatment treated with Pioglitazone or any other PPAR agonist medication.
14. Current use of of MAO Inhibitors, statins, and anticoagulants (e.g. warfarin)

Where this trial is running

Boston, Massachusetts

• The Dauten Family Center for Bipolar Treatment Innovation at Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Andrew A. Nierenberg, M.D. — Massachusetts General Hospital
• Study coordinator: Alec P Shannon, B.S.

Conditions Bipolar Disorder; Depressive Episode; Bezafibrate