BezafibrateTreatment for Bipolar Depression: A Proof of Concept Study
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Pan-PPAR Agonist Treatment for Bipolar Depression: A Proof of Concept Study|
- Change from Baseline to Week 8 in Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Baseline and Week 8 ]The primary efficacy measure will be the change in MADRS score.
- Change from Baseline to Week 8 in Clinical Global Impressions Bipolar Scale (CGI-BP-S) score [ Time Frame: Baseline and Week 8 ]Secondary efficacy measure will be change in CGI-BP-S score.
- Adiponectin Level at Baseline and Week 8 [ Time Frame: Baseline and Week 8 ]We will measure adiponectin as a well-established biomarker for the effect of bezafibrate on PPAR and examine changes in adiponectin as a mediator of changes in mood symptoms.
|Study Start Date:||September 2015|
|Estimated Study Completion Date:||June 2019|
|Estimated Primary Completion Date:||June 2018 (Final data collection date for primary outcome measure)|
Experimental: Bipolar I Disorder
30 currently depressed patients with DSM-IV bipolar I disorder who are currently taking an adequate dose of an FDA-approved anti-manic medication will receive Bezafibrate treatment
30 patients with Bipolar I 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.
Other Name: Bezalip
Please refer to this study by its ClinicalTrials.gov identifier: NCT02481245
|Contact: Steven Dufour, B.A.||firstname.lastname@example.org|
|United States, Massachusetts|
|The Dauten Family Center for Bipolar Treatment Innovation at Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Steven Dufour, B.A. 617-643-6194 email@example.com|
|Principal Investigator:||Andrew A. Nierenberg, M.D.||Massachusetts General Hospital|