Adjunctive Isradipine for the Treatment of Bipolar Depression

NCT01784666 | Terminated Phase 2 Results DMC

• 1 other identifier: 2012-P-002449/1
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates the medication isradipine, which is currently approved by the FDA to treat high blood pressure, in the treatment of depression in bipolar disorder. Isradipine or placebo (contains no active medication) will be used as an "add-on" to lithium, valproate, and/or atypical antipsychotics for individuals currently experiencing a major depressive episode. Our hypothesis is that isradipine will be superior to placebo in improving depressive symptoms.

Conditions

Bipolar Disorder

Keywords

Bipolar Disorder; Depression; Lithium; Valproate; Isradipine

Outcome Measures

Primary Outcomes (1)

• Change in MADRS (4 Weeks)

  Change in Montgomery-Asberg Depression Rating Scale (MADRS) in isradipine-treated epochs versus placebo-treated epochs. These scores represent total scores, and on the MADRS total scores range from 0-60. A higher score indicates increased depression severity.

  Baseline vs week 4 (and, for placebo nonresponders in 1st 4 weeks, week 8 vs week 4)

Study Arms (3)

Isradipine-Isradipine

EXPERIMENTAL

Subjects will receive isradipine in phase 1 (4 weeks) and phase 2 (4 weeks)

Drug: Isradipine

Placebo -> Isradipine

EXPERIMENTAL

Placebo non-responders after the 1st 4 weeks will be re-randomized 1:1 to placebo or isradipine for the next 4 weeks

Drug: Isradipine; Drug: Placebo

Placebo-Placebo

PLACEBO COMPARATOR

Placebo nonresponders for the 1st 4 weeks will be re-randomized 1:1 to placebo or isradipine for the subsequent 4 weeks

Drug: Placebo

Interventions

Isradipine DRUG

The study uses the Sequential Parallel Comparison design (SPCD), with two 4-week phases: n=30 subjects are randomized 1:1 to isradipine versus placebo add-on for 4 weeks, with the placebo nonresponders re-randomized 1:1 for a further 4 weeks. The SPCD will allow us to pool data from both phases to estimate the isradipine treatment effect. Subjects who respond in phase 1, and all subjects who receive isradipine in phase 1, continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed.

Isradipine-Isradipine; Placebo -> Isradipine

Placebo DRUG

Subjects (n=15) are randomized to placebo add-on for 4 weeks, with the nonresponders re-randomized 1:1 to isradipine vs placebo for a further 4 weeks. Subjects who respond in phase 1 continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed.

Placebo -> Isradipine; Placebo-Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65
• written informed consent
• meets Diagnostic and Statistical Manual-IV (DSM-IV) criteria (by Structured Clinical Interview for Diagnostic and Statistical Manual - IV -I/P (SCID)) for bipolar I disorder, current episode depressed
• Montgomery-Asberg Depression Scale (MADRS) score of at least 20 (i.e., moderate depression) and no greater than 34 (i.e., severe depression) at screen and baseline visit
• Young Mania Rating Scale (YMRS) score \< 12 at screen and baseline visit
• currently treated with a lithium preparation (carbonate or citrate) at stable dose for at least 4 wks with level \>0.6 and \<1.0; and/or valproate at stable dose for at least 4 wks at level \>60 and \<110; and/or other atypical antipsychotic at stable dose for at least 4 weeks (at least minimum FDA-labeled dose)
• Caucasian by self-report - please see discussion below

You may not qualify if:

• Psychotic features in the current episode, as assessed by YMRS item #8 \> 6 \[where treatment guidelines urge use of antipsychotics that may confound isradipine results\]
• felt by the study clinician to require inpatient hospitalization for adequate management (to include serious suicide or homicide risk, as assessed by evaluating clinician)
• or more failed pharmacologic interventions in the current major depressive episode, excluding lithium/valproate/other atypical antipsychotic \[response rates for these subjects is likely to be extremely low and would require a substantially larger-scale study to identify treatment effects\]
• obsessive-compulsive disorder, or any diagnosis of a DSM-IV anxiety disorder where the anxiety disorder and not bipolar disorder is the primary focus of clinical attention
• current substance use disorder other than nicotine, by SCID-I/P
• a primary clinical diagnosis of a personality disorder, or comorbid diagnosis of antisocial or borderline personality disorder
• pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy)
• women who are breastfeeding
• other unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease, based on review of medical history, physical examination, and screening laboratory tests (this will include any clinical or laboratory evidence of hypothyroidism; if maintained on thyroid medication must be euthyroid for at least 1 month before Visit 1)
• history of hypertension or current treatment for hypertension
• current use of isradipine or history of anaphylactic reaction or intolerance to isradipine or any component of the preparation
• ECG abnormalities at entry: prolonged QTC interval or complete or incomplete bundle branch block
• patients who have taken an investigational psychotropic drug within the last 3 months
• patients receiving other excluded antipsychotics or antidepressants within 2 weeks prior to study entry
• patients requiring continued treatment with excluded medications (see below).

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Bipolar Disorder; Depression

Interventions

Isradipine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The study was terminated early by the investigator because delays in study initiation and insufficient recruitment. Our statisticians have advised that this analysis is uninformative.

Results Point of Contact

• Title: Dr. Roy Perlis
• Organization: Massachusetts General Hospital, Center for Quantitative Health

rperlis@partners.org

617-643-6310

Study Officials

• Roy H Perlis, MD, MSc

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Study Record Dates

• First Submitted: February 4, 2013
• First Posted: February 6, 2013
• Study Start: February 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 20, 2017
• Results First Posted: April 20, 2017

Record last verified: 2017-04

Locations

US (1)