Adjunctive Isradipine for the Treatment of Bipolar Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Roy Perlis, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01784666
First received: February 4, 2013
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Bipolar Disorder
Drug: Isradipine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Adjunctive Isradipine for the Treatment of Bipolar Depression

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in MADRS (4 weeks) [ Time Frame: Baseline vs week 4 (and, for placebo nonresponders in 1st 4 weeks, week 8 vs week 4) ] [ Designated as safety issue: No ]
    Change in Montgomery-Asberg Depression Rating Scale (MADRS) in isradipine-treated epochs versus placebo-treated epochs


Estimated Enrollment: 30
Study Start Date: February 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Isradipine-Isradipine
Subjects will receive isradipine in phase 1 (4 weeks) and phase 2 (4 weeks)
Drug: Isradipine
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.
Experimental: Placebo -> Isradipine
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
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.
Drug: Placebo
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 Comparator: Placebo-Placebo
Placebo nonresponders for the 1st 4 weeks will be re-randomized 1:1 to placebo or isradipine for the subsequent 4 weeks
Drug: Placebo
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.

Detailed Description:

Primary Aim: To estimate the antidepressant efficacy of isradipine versus placebo as an adjunct to lithium, valproate, and/or other atypical antipsychotics among individuals with bipolar I disorder in a nonpsychotic major depressive episode.

Hypothesis: Isradipine will be superior to placebo in improvement of depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale (MADRS).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-65
  • written informed consent
  • meets DSM-IV criteria (by SCID-I/P) for bipolar I disorder, current episode depressed
  • MADRS score of at least 20 (i.e., moderate depression) and no greater than 34 (i.e., severe depression) at screen and baseline visit
  • 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

Exclusion Criteria:

  • 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)
  • 3 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 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).

Excluded medications: antidepressants, antipsychotics, and anticonvulsants (other than valproate), which could influence calcium signaling or impact mood; other calcium channel blockers; any other antihypertensive because of the risk of cause hypotension; any other drug known to interact with isradipine. Benzodiazepines or other sedative-hypnotic agents (e.g., zolpidem) may not be initiated after study entry; subjects requiring these agents will be removed from the study. Allowed: Sedative-hypnotic agents if dosage has been stable for 4 weeks prior to study entry; thyroid or estrogen replacement provided dosage has been stable for 3 months. Acceptable anticonvulsants include lamotrigine, valproate, gabapentin, topiramate, oxcarbazepine, carbamazepine.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01784666

Contacts
Contact: Roy H Perlis, MD, MSc rperlis@chgr.mgh.harvard.edu
Contact: Ashlee Roberson, BA aroberson2@mgh.harvard.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Roy H Perlis, MD MSc    617-726-7426    rperlis@chgr.mgh.harvard.edu   
Contact: Ashlee Roberson, BA    617-643-6310    aroberson2@mgh.harvard.edu   
Principal Investigator: Roy H Perlis, MD, MSc         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Roy H Perlis, MD, MSc Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Roy Perlis, Associate Professor of Psychiatry, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01784666     History of Changes
Other Study ID Numbers: 2012-P-002449/1
Study First Received: February 4, 2013
Last Updated: June 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Bipolar Disorder
Depression
Lithium
Valproate
Isradipine

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Isradipine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on August 20, 2014