Clinical trial NCT02481245: BezafibrateTreatment for Bipolar Depression: A Proof of Concept Study
Official title: A Pan-PPAR Agonist Treatment for Bipolar Depression: A Proof of Concept Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Bipolar Disorder
Depressive Episode
Keywords: Bipolar Disorder
Bezafibrate
Depressive Episode
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Brain & Behavior Research Foundation
name: J Willard and Alice S. Marriott Foundation
First posted: 2015-06-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 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)

Primary outcomes:
measure: Change from Baseline to Week 8 in Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Change from Baseline to Week 8 in Clinical Global Impressions Bipolar Scale (CGI-BP-S) score
timeFrame: Baseline and Week 8
measure: Adiponectin Level at Baseline and Week 8
timeFrame: Baseline and Week 8
Other outcomes:
Locations:
city: Boston
country: United States
facility: The Dauten Family Center for Bipolar Treatment Innovation at Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Andrew A. Nierenberg, M.D.
role: PRINCIPAL_INVESTIGATOR
References: