Adjunctive Isradipine for the Treatment of Bipolar Depression

Mass General Brigham

Status and phase: Terminated; Phase 2

Conditions: Bipolar Disorder

Treatments: Drug: Isradipine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01784666

2012-P-002449/1

Details and patient eligibility

About

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.

Full 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).

Enrollment: 2 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

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 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).

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2 participants in 3 patient groups, including a placebo group

Isradipine-Isradipine

Experimental group

Description:

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

Treatment:

Drug: Isradipine

Placebo -> Isradipine

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: Isradipine

Placebo-Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo