Magnetic Resonance Imaging Study of Lisdexamfetamine for Bipolar Depression

NCT01051440 | Terminated Phase 4 Results

• 1 other identifier: 00517
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

There have been reports that stimulants may be effective for bipolar depression without triggering mania. This study will examine whether lisdexamfetamine can improve depressive symptoms over the course of eight weeks. Lisdexamfetamine is a prodrug stimulant that is currently approved for attention deficit hyperactivity disorder (ADHD). Participants take the study drug or placebo in addition to a mood stabilizer. The study includes functional magnetic resonance imaging and magnetic resonance spectroscopy to determine whether the medication alters the response to affective stimuli or glutamate, glutamine, or gamma aminobutyric acid (GABA) levels. Neuropsychological testing is also included to determine whether the study drug improves memory and attention in this population. The primary hypothesis is that lisdexamfetamine is clinically effective in this population. The secondary hypothesis is that it will result in an increased response to affective stimuli and altered neurotransmitter levels in the anterior cingulate cortex.

Conditions

Bipolar Depression

Keywords

lisdexamfetamine; vyvanse; bipolar disorder; depression; stimulant; magnetic resonance spectroscopy; functional magnetic resonance imaging; neuropsychological testing

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery Asberg Depression Rating Scale (MADRS) Score Over Time.

  The change in MADRS score from the baseline visit to the week 8 visit is reported. The MADRS is a clinician-rated scale that consists of 10 items rated on a from 0 to 6 (maximum score of 60), with higher scores indicating greater symptom severity. An increase in score indicates a worsening of symptoms whereas a decrease indicates an improvement in symptoms.

  baseline and 8 weeks

Secondary Outcomes (2)

• Change in Clinical Global Impressions Severity (CGI-S) Score.

  baseline and week 8

• Change in Clinical Global Impressions Improvement (CGI-I) Score.

  week 1 and week 9

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Subjects will receive placebo for lisdexamfetamine.

Drug: Placebo

Lisdexamfetamine

ACTIVE COMPARATOR

Subjects will start with 20 mg per day of lisdexamfetamine and may increase to a maximum of 40 mg.

Drug: Lisdexamfetamine

Interventions

Lisdexamfetamine DRUG

Start at 20 mg daily. Increased to a maximum of 40 mg daily. Can be decreased in 10 mg increments.

Also known as: Vyvanse

Lisdexamfetamine

Placebo DRUG

Subjects will receive placebo matched to lisdexamfetamine.

Placebo

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 21 to 50 years.
• Diagnosed with Bipolar Disorder I or II disorder.
• Currently in the depressive phase of the illness.
• Montgomery Asberg Depression Rating Scale (MADRS) score greater than 15.
• Medication regimen (Lamotrigine, Valproate, Lithium, either alone or in combination with atypical antipsychotics, or typical antipsychotics) at stable doses for at least one month.
• Has an established residence and phone.
• Capable of providing informed consent.

You may not qualify if:

• Met Diagnostic and Statistical Manual 4th edition (DSM-IV-TR) criteria for rapid cycling within the 6 months prior to enrolling in the study.
• History of psychotic symptoms at any point during the subject's illness.
• Met DSM-IV-TR criteria for alcohol or substance (except for nicotine) dependence or abuse within the past 6 months.
• Lifetime history of amphetamine abuse or dependence.
• Subject has a lifetime history of stimulant-induced mania
• History of seizures, including febrile seizures in childhood.
• Young Mania Rating Scale (YMRS) greater than 8.
• History of significant coronary artery disease, angina, untreated or inadequately treated thyroid disease (less than 1 month chemically euthyroid), type I diabetes, autoimmune disease, glaucoma, hypertension, seizures, or other medical condition(s) which in the opinion of the principal investigator is likely to significantly impact the subject's mood or potential response to the study medication.
• Electrocardiogram (ECG) with significant arrhythmias or conduction abnormalities, which in the opinion of the physician investigator preclude study participation; uncontrolled hypertension (\>160/100) or tachycardia (heart rate \>110).
• Female subjects who are peri or post-menopausal.
• Subjects taking Ritalin or other stimulants, theophylline, steroids, atomoxetine, cholinesterase inhibitors, memantine, modafinil, warfarin, anticonvulsants, clonidine, theophylline, monoamine oxidase inhibitors, and pseudoephedrine, or other medications that are likely to significantly interact (either pharmacokinetically or pharmacodynamically) with the subject's mood or Lisdexamfetamine.
• Subject regularly (more than 4 days per week) ingests more than four caffeine containing drinks per day.
• Pregnancy.
• In women of childbearing potential, an unwillingness to avoid pregnancy for the duration of the study.
• Active suicidal ideation.

Sponsors & Collaborators

• Steward St. Elizabeth's Medical Center of Boston, Inc.: lead
• Shire: collaborator

Study Sites (1)

Steward St. Elizabeth's Medical Center

Boston, Massachusetts, 02135, United States

Location

MeSH Terms

Conditions

Bipolar Disorder; Depression

Interventions

Lisdexamfetamine Dimesylate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dextroamphetamine; Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Limitations and Caveats

The study was terminated before completion due to low enrollment. One subject was randomized to lisdexamfetamine and one was randomized to placebo. Therefore, it was not possible to obtain complete data.

Results Point of Contact

• Title: Tara Lauriat
• Organization: Steward St. Elizabeth's Medical Center

tara.lauriat@steward.org

617-789-2404

Study Officials

• Michael E Henry, MD

  Steward St. Elizabeth's Medical Center of Boston, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 14, 2010
• First Posted: January 18, 2010
• Study Start: February 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: January 30, 2013
• Results First Posted: January 30, 2013

Record last verified: 2012-12

Locations

US (1)