Magnetic Resonance Imaging Study of Lisdexamfetamine for Bipolar Depression

This study has been terminated.
(Slow enrollment)
Sponsor:
Collaborator:
Shire
Information provided by (Responsible Party):
Michael Henry, MD, Steward St. Elizabeth's Medical Center of Boston, Inc.
ClinicalTrials.gov Identifier:
NCT01051440
First received: January 14, 2010
Last updated: December 19, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Bipolar Depression
Drug: Lisdexamfetamine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Magnetic Resonance Spectroscopy and fMRI Study of the Effects of Lisdexamfetamine on Bipolar Depression

Resource links provided by NLM:


Further study details as provided by Steward St. Elizabeth's Medical Center of Boston, Inc.:

Primary Outcome Measures:
  • Change in Montgomery Asberg Depression Rating Scale (MADRS) Score Over Time. [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Clinical Global Impressions Severity (CGI-S) Score. [ Time Frame: baseline and week 8 ] [ Designated as safety issue: No ]
    The CGI-S score reflects the clinician's overall impression of the patient's functional status. The scoring for the single item ranges from 1 with an anchor of "normal, not at all ill" to 7 with an anchor of "among the most extremely ill patients". Thus, higher scores indicate greater severity of symptoms.

  • Change in Clinical Global Impressions Improvement (CGI-I) Score. [ Time Frame: week 1 and week 9 ] [ Designated as safety issue: No ]
    The CGI-I score indicates the clinician's overall assessment of improvement in function from one visit to the next. The single item is scored from 1 to 7 with anchor points ranging from very much improved (1) to very much worse (7). A decrease in score reflects an improvement in functional status.


Enrollment: 2
Study Start Date: February 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Subjects will receive placebo for lisdexamfetamine.
Drug: Placebo
Subjects will receive placebo matched to lisdexamfetamine.
Active Comparator: Lisdexamfetamine
Subjects will start with 20 mg per day of lisdexamfetamine and may increase to a maximum of 40 mg.
Drug: Lisdexamfetamine
Start at 20 mg daily. Increased to a maximum of 40 mg daily. Can be decreased in 10 mg increments.
Other Name: Vyvanse

  Eligibility

Ages Eligible for Study:   21 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Met Diagnostic and Statistical Manual 4th edition (DSM-IV-TR) criteria for rapid cycling within the 6 months prior to enrolling in the study.
  • Meets DSM-IV-TR criteria for Schizophrenia, Schizoaffective disorder, Post-Traumatic Stress disorder, Obsessive-Compulsive disorder, or Eating disorder. Co-morbid anxiety disorders are not a reason for exclusion.
  • 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.
  • History of homicidal ideation.
  • Allergy or other clinical condition which prohibits the use of all of the approved mood stabilizers or Lisdexamfetamine.
  • Metal in the body (e.g. history of working as a sheet metal worker) or pacemaker which is a contra-indication to magnetic resonance imaging (MRI).
  • Significant claustrophobia.
  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: NCT01051440

Locations
United States, Massachusetts
Steward St. Elizabeth's Medical Center
Boston, Massachusetts, United States, 02135
Sponsors and Collaborators
Steward St. Elizabeth's Medical Center of Boston, Inc.
Shire
Investigators
Principal Investigator: Michael E Henry, MD Steward St. Elizabeth's Medical Center of Boston, Inc.
  More Information

No publications provided

Responsible Party: Michael Henry, MD, Principal Investigator, Steward St. Elizabeth's Medical Center of Boston, Inc.
ClinicalTrials.gov Identifier: NCT01051440     History of Changes
Other Study ID Numbers: 00517
Study First Received: January 14, 2010
Results First Received: July 30, 2012
Last Updated: December 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Steward St. Elizabeth's Medical Center of Boston, Inc.:
lisdexamfetamine
vyvanse
bipolar disorder
depression
stimulant
magnetic resonance spectroscopy
functional magnetic resonance imaging
neuropsychological testing

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Dextroamphetamine
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014