BezafibrateTreatment for Bipolar Depression: A Proof of Concept Study
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-65
SponsorMassachusetts General Hospital
About this trial
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
This trial does not accept healthy volunteersQualifiers
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 two weeks prior to enrollment
Disqualifiers
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
Primary diagnosis of anxiety disorders or patients where the anxiety disorder is the primary 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 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
Trial design
Design model
Single group
Treatments tested in this trial
Bezafibrate
Drug30 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.
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: Bipolar I and Bipolar II DisorderExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Change from Baseline to Week 8 in Montgomery-Åsberg Depression Rating Scale (MADRS)
The primary efficacy measure will be the change in MADRS score.
Time frame
Baseline and Week 8Secondary outcomes
1
Change from Baseline to Week 8 in Clinical Global Impressions Bipolar Scale (CGI-BP-S) score
Secondary efficacy measure will be change in CGI-BP-S score.
Time frame
Baseline and Week 82
Adiponectin Level at 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.
Time frame
Baseline and Week 8Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Massachusetts General Hospital
Lead sponsor
Brain & Behavior Research Foundation
Collaborator
J Willard and Alice S. Marriott Foundation
Collaborator
Source ClinicalTrials.gov