BezafibrateTreatment for Bipolar Depression: A Proof of Concept Study

Phase

Condition

Bipolar Disorder

Mood Disorders

Treatment

Bezafibrate

Clinical Study ID

NCT02481245

2014P000862

Ages 18-65
All Genders

Study Summary

We propose to test the hypothesis that bezafibrate, a pan-PPAR agonist, may be effective and safe for bipolar depression with the following specific aims:

Aim #1. Proof-of-Concept Safety and Tolerability Aim: To assess the safety and tolerability of bezafibrate added to anti-manic medication for bipolar depression, especially with regard to worsening manic symptoms and suicidal ideation.

We will conduct a phase IIa, 8-week, open pilot trial of bezafibrate added to FDA-approved anti-manic medication in 30 participants with bipolar depression. We will monitor changes in manic symptoms (Young Mania Rating Scale), suicidal ideation, cognitive functioning specifically in attention and verbal memory, and treatment emergent adverse events (SAFTEE). We will also monitor changes in the Framingham Cardiovascular Risk Score.

Aim #2. Preliminary Assessment of Efficacy: To assess the antidepressant efficacy of bezafibrate added to anti-manic medication for acute bipolar I major depressive episodes.

Hypothesis: The bezafibrate group will have a statistically significant decrease in the Montgomery Asberg Rating Scale (MADRS) Scores over 8 weeks. The results of this proof-of concept phase IIa study will help us to plan a placebo-controlled randomized trial. In summary, we propose an 8-week, proof-of-concept open pilot trial of an adjunctive pan-PPAR agonist, bezafibrate, for 30 patients with an acute bipolar I major depressive episode. The study may have a profound impact on the development of a novel treatment consistent with the mitochondrial dysregulation hypothesis of bipolar disorder and, to the best of our knowledge, will be the first proof-of-concept trial to assess a pan-PPAR agonist for bipolar disorder.

Eligibility Criteria

Inclusion

Inclusion Criteria:

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

Exclusion

Exclusion Criteria:

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) delusionaldisorder, (8) psychotic disorders not elsewhere classified, (9) acute bereavement, (10) severe borderline or antisocial personality disorder, (11) OCD or OCD-spectrumdisorders
Primary diagnosis of anxiety disorders or patients where the anxiety disorder is theprimary focus of treatment
Patients with mood congruent or mood incongruent psychotic features
Pregnant women or women of child bearing potential who are not using a medicallyaccepted means of contraception (e.g. oral contraceptives, intrauterine device,barrier methods, or total abstinence from intercourse; Depo Provera is acceptable ifit is started 3 months prior to enrollment). Women who are nursing
Patients who are a serious suicide or homicide risk
Suspected or known clinically unstable systemic medical disorder including epilepsy,untreated endocrine disease, unstable angina, recent ulcers or significantesophagitis
Conditions which may be negatively affected by bezafibrate treatment, such ashepatobiliary disease
Clinical or laboratory evidence of hypothyroidism (if maintained on thyroidmedication must be euthyroid for at least 1 month before Visit 1)
Subjects having failed two or more trials of somatic therapy (i.e., medications forbipolar depression or FDA-approved devices) during the current bipolar depressiveepisode
Current use of a fibrate or history of anaphylactic reaction or intolerance tofibrates or any component of the preparation
History of significant treatment non-adherence or situations where the subjects isunlikely to adhere to treatment, in the opinion of the investigator
History of stroke or cerebrovascular disease
Type 1 or Type II Diabetes requiring medication treatment treated with Pioglitazoneor any other PPAR agonist medication.
Current use of of MAO Inhibitors, statins, and anticoagulants (e.g. warfarin)

Study Design