A Pan-PPAR Agonist Treatment for Bipolar Depression: A Proof of Concept Study
Massachusetts General Hospital
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
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- No
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…
Interventions
- DrugBezafibrate
30 patients with Bipolar I or Bipolar II disorder who are experiencing an acute bipolar depressive episode will be given bezafibrate XR 400 mg daily added on to adequate doses of an FDA-approved anti-manic medication.
Location
- The Dauten Family Center for Bipolar Treatment Innovation at Massachusetts General HospitalBoston, Massachusetts