Magnetic Resonance Imaging Study of Lisdexamfetamine for Bipolar Depression

• Sponsor: Steward St. Elizabeth's Medical Center of Boston, Inc. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01051440
• Collaborator: Shire (Industry)
• Enrollment: 2
• Location: 1
• Arms: 2
• Duration (Months): 15.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Depression	Drug: Lisdexamfetamine; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Magnetic Resonance Spectroscopy and fMRI Study of the Effects of Lisdexamfetamine on Bipolar Depression
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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 Names: Vyvanse

Outcome Measures

Primary Outcome Measures

1. Change in Montgomery Asberg Depression Rating Scale (MADRS) Score Over Time. [baseline and 8 weeks]

   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

1. Change in Clinical Global Impressions Severity (CGI-S) Score. [baseline and week 8]

   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.

2. Change in Clinical Global Impressions Improvement (CGI-I) Score. [week 1 and week 9]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Henry, MD, Principal Investigator, Steward St. Elizabeth's Medical Center of Boston, Inc.
• ClinicalTrials.gov Identifier: NCT01051440
• Other Study ID Numbers: 00517
• First Posted: Jan 18, 2010
• Last Update Posted: Jan 30, 2013
• Last Verified: Dec 1, 2012

• Keywords provided by Michael Henry, MD, Principal Investigator, 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: Depression; Depressive Disorder; Bipolar Disorder; Lisdexamfetamine Dimesylate

Study Results

Participant Flow

Recruitment Details	The recruitment period began in June 2010 and concluded in early 2012. Recruitment was through media advertisements and patients in the hospital outpatient clinic. Out of hundreds of individuals who were pre-screened by telephone, 31 were invited to the clinic for screening visits.
Pre-assignment Detail	Participants who were not on an approved mood stabilizer (lithium, valproate, or lamotrigine) at the time of enrollment were eligible for a one-month lead in to start a mood stabilizer prior to randomization. Several participants were excluded due to psychiatric co-morbidity, unclear diagnosis, history of stimulant use, or medical concerns.

Arm/Group Title	Placebo	Lisdexamfetamine
Arm/Group Description	Subjects received matched placebo for lisdexamfetamine.	Subjects started with 20 mg per day of lisdexamfetamine and could have the dose increased to a maximum of 40 mg based on change in clinical response and adverse events.
Period Title: Overall Study
STARTED	1	1
COMPLETED	1	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Lisdexamfetamine	Total
Arm/Group Description	Subjects received matched placebo for lisdexamfetamine.	Subjects started with 20 mg per day of lisdexamfetamine and could have the dose increased to a maximum of 40 mg based on change in clinical response and adverse events.	Total of all reporting groups
Overall Participants	1	1	2
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	1 100%	2 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38 (0)	30 (0)	34 (5.7)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	1 100%	2 100%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	2 100%

Outcome Measures

1. Primary Outcome

Title	Change in Montgomery Asberg Depression Rating Scale (MADRS) Score Over Time.
Description	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.
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

All participants randomized to lisdexamfetamine or placebo were included.

Arm/Group Title	Placebo	Lisdexamfetamine
Arm/Group Description	Subjects received matched placebo for lisdexamfetamine.	Subjects started with 20 mg per day of lisdexamfetamine and could have the dose increased to a maximum of 40 mg based on change in clinical response and adverse events.
Measure Participants	1	1
Number [units on a scale]	4 (0)	-22 (0)

2. Secondary Outcome

Title	Change in Clinical Global Impressions Severity (CGI-S) Score.
Description	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.
Time Frame	baseline and week 8

Outcome Measure Data

Analysis Population Description

All participants who were randomized to lisdexamfetamine or placebo were included.

Arm/Group Title	Placebo	Lisdexamfetamine
Arm/Group Description	Subjects received matched placebo for lisdexamfetamine.	Subjects started with 20 mg per day of lisdexamfetamine and could have the dose increased to a maximum of 40 mg based on change in clinical response and adverse events.
Measure Participants	1	1
Number [units on a scale]	1	-2

3. Secondary Outcome

Title	Change in Clinical Global Impressions Improvement (CGI-I) Score.
Description	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.
Time Frame	week 1 and week 9

Outcome Measure Data

Analysis Population Description

All participants who were randomized to lisdexamfetamine or placebo were included.

Arm/Group Title	Placebo	Lisdexamfetamine
Arm/Group Description	Subjects received matched placebo for lisdexamfetamine.	Subjects started with 20 mg per day of lisdexamfetamine and could have the dose increased to a maximum of 40 mg based on change in clinical response and adverse events.
Measure Participants	1	1
Number [units on a scale]	0	-2

Adverse Events

Arm/Group Title	Placebo		Lisdexamfetamine
Arm/Group Description	Subjects received matched placebo for lisdexamfetamine.		Subjects started with 20 mg per day of lisdexamfetamine and could have the dose increased to a maximum of 40 mg based on change in clinical response and adverse events.
All Cause Mortality
	Placebo		Lisdexamfetamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Lisdexamfetamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Lisdexamfetamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)

Limitations/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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.