Clinical trial NCT01051440: Magnetic Resonance Imaging Study of Lisdexamfetamine for Bipolar Depression
Official title: A Magnetic Resonance Spectroscopy and fMRI Study of the Effects of Lisdexamfetamine on Bipolar Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Bipolar Depression
Keywords: lisdexamfetamine
vyvanse
bipolar disorder
depression
stimulant
magnetic resonance spectroscopy
functional magnetic resonance imaging
neuropsychological testing
Lead sponsor: Steward St. Elizabeth's Medical Center of Boston, Inc.
Sponsor class: OTHER
Collaborators: name: Shire
First posted: 2010-01-18
Enrollment: 2
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change in Montgomery Asberg Depression Rating Scale (MADRS) Score Over Time.
timeFrame: baseline and 8 weeks
Secondary outcomes:
measure: Change in Clinical Global Impressions Severity (CGI-S) Score.
timeFrame: baseline and week 8
measure: Change in Clinical Global Impressions Improvement (CGI-I) Score.
timeFrame: week 1 and week 9
Other outcomes:
Locations:
city: Boston
country: United States
facility: Steward St. Elizabeth's Medical Center
state: Massachusetts
Study officials:
affiliation: Steward St. Elizabeth's Medical Center of Boston, Inc.
name: Michael E Henry, MD
role: PRINCIPAL_INVESTIGATOR
References: