Magnetic Resonance Imaging Study of Lisdexamfetamine for Bipolar Depression

Bipolar Depression Clinical Trial

Official title:

A Magnetic Resonance Spectroscopy and fMRI Study of the Effects of Lisdexamfetamine on Bipolar Depression

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01051440
• Other study ID #: 00517
• Status: Terminated
• Phase: Phase 4
• First received: January 14, 2010
• Last updated: December 19, 2012
• Start date: February 2010
• Est. completion date: June 2011

Study information

• Verified date: December 2012
• Source: Steward St. Elizabeth's Medical Center of Boston, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 50 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Depression
• Bipolar Disorder
• Depression
• Depressive Disorder

Intervention

Drug:
• Lisdexamfetamine
Start at 20 mg daily. Increased to a maximum of 40 mg daily. Can be decreased in 10 mg increments.
• Placebo
Subjects will receive placebo matched to lisdexamfetamine.

Locations

Country	Name	City	State
United States	Steward St. Elizabeth's Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Steward St. Elizabeth's Medical Center of Boston, Inc.	Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change in Clinical Global Impressions Severity (CGI-S) Score.	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.	baseline and week 8	No
Secondary	Change in Clinical Global Impressions Improvement (CGI-I) Score.	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.	week 1 and week 9	No