BezafibrateTreatment for Bipolar Depression: A Proof of Concept Study
| Status: | Recruiting |
|---|---|
| Conditions: | Depression, Psychiatric, Bipolar Disorder |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 4/17/2018 |
| Start Date: | September 2015 |
| End Date: | June 2019 |
| Contact: | Steven Dufour, B.A. |
| Email: | sdufour@partners.org |
| Phone: | 617-643-6194 |
A Pan-PPAR Agonist Treatment 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.
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.
Inclusion Criteria:
1. Men or women between the ages of 18 and 65 (inclusive)
2. DSM IV diagnosis of Bipolar Disorder Type I
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 II, (2) Bipolar NOS, (3) Cyclothymia, (4)
Schizoaffective Disorder, (5) organic mental disorders, (6) substance use disorders,
including alcohol, active within the 3 months, (7) schizophrenia, (8) delusional
disorder, (9) psychotic disorders not elsewhere classified, (10) acute bereavement,
(11) severe borderline or antisocial personality disorder, (12) 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. History of Type 1 or Type II Diabetes
14. Current use of of MAO Inhibitors, statins, and anticoagulants (e.g. warfarin)
We found this trial at
1
site
50 Staniford Street
Boston, Massachusetts 02114
Boston, Massachusetts 02114
Phone: 617-643-6194
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