Clinical trial NCT00741598: Efficacy and Safety of Galantamine for Improving Dysfunction in People With Bipolar Disorder
Official title: The Efficacy and Safety of Galantamine for Dysfunction in Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Massachusetts General Hospital
First posted: 2008-08-26
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will examine whether extended release galantamine, a drug approved by the Food and Drug Administration to reduce cognitive impairments in people with Alzheimer's disease, can perform the same function in stable people with bipolar disorder.

Detailed description: Approximately 2.6% of Americans age 18 and older, or 5.7 million people, suffer from bipolar disorder. The manic and depressive episodes associated with bipolar disorder prevent normal functioning in individuals with the disorder, but functional impairment can occur even when bipolar disorder is in remission. Previous research indicates that this impairment in stable individuals with bipolar disorder is linked to neurocognitive deficits, such as problems with memory and attention. The drug extended release galantamine increases the level of acetylcholine, a neurotransmitter important for memory, available in the brain. This drug has already been approved by the FDA to treat neurocognitive impairment in Alzheimer's disease patients. This study will examine whether administering the drug to individuals with bipolar disorder who are in remission can also reduce their neurocognitive deficits and improve the quality of their life. The study will also examine the safety of the drug for use in the obsessive-compulsive disorder population.

Participation in this study will last about 18 weeks and will involve six study visits. Each of the first two visits will include 2 hours of clinical, physical, and self-report tests, the first for screening and the second to establish physical and mental health baseline measurements. Participants will then be randomly assigned to receive either galantamine or placebo daily for 16 weeks, and they will be provided with enough of the assigned pill to last until the next visit. Half hour visits on Weeks 4, 8, and 12 will consist of psychological self-report tests and interviews, clinical assessment of side effects from the drug, and the determination by the examining doctor and participant whether to increase, decrease, or maintain the same level of the drug. Participants will also be given enough of the drug to last until the next visit. The final visit, on Week 16, will last 2 hours and will consist of the same tests administered at the baseline visit in addition to the neuropsychological tests administered at the screening visit. The full range of tests will measure physical health, verbal memory, mental flexibility, attention, life impairment, and life satisfaction.

Eligibility criteria: Inclusion Criteria:

* DSM-IV diagnosis of Bipolar I disorder or Bipolar II disorder
* A baseline Hamilton-D 17 score of less than 10 at screening visit
* A baseline Young Mania Rating Scale (YMRS) score of less than 10 at screening visit
* No acute episodes of depression or mania for the previous 12 weeks
* Score of 17 or higher on the Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire
* Treated with psychiatric medications, alone or in combination, having only minimal, mild or moderate cognitive burden \[as determined by a score of less than 3.5 on the MGH Cognitive Impact of Psychotropic Medications Scale (CIPMS).
* Able to understand English

Exclusion Criteria:

* DSM-IV diagnosis of Bipolar NOS, Cyclothymia, or Schizoaffective Bipolar type.
* Meets DSM-IV criteria for acute manic, depressive, or mixed bipolar episode or had met full criteria for 2 consecutive weeks within the past 12 weeks prior to assessment
* Treated with psychiatric medications with large effects on cognition (as determined by a MGH Cognitive Impact of Psychotropic Medications Scale score of 4.0 or above)
* Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy)
* Serious suicide or homicide risk
* Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
* History of seizure disorder, brain injury, or any known neurological disease (multiple sclerosis, degenerative disease such as ALS, Parkinson disease and any movement disorders, etc)
* The following DSM-IV diagnoses: 1) organic mental disorders; 2) any diagnosis of dementia; 3) substance use disorders, including alcohol, active within the last year; 4) schizophrenia; 5) delusional disorder; 6) psychotic disorders not elsewhere classified; 7) schizoaffective disorder; 8) major depressive disorder; 9) acute bereavement; 10) severe borderline or antisocial personality disorder
* Presence of mood congruent or mood incongruent psychotic features
* Clinical or laboratory evidence of hypothyroidism
* History of multiple adverse drug reactions, allergy to galantamine or other AChEIs
* Current use, or use within the last week, of excluded drugs (psychotropic medications and other central nervous system (CNS)-active drugs)
* Taken an investigational psychotropic drug within the last year
* Had electroconvulsive therapy (ECT) within the 6 months preceding enrollment

Primary outcomes:
measure: Scores on the California Verbal Learning Test (CVLT-II) at Screening and Week 16
timeFrame: Measured at screening and Week 16
measure: Scores on the Wisconsin Card Sorting Test (WCST) at Screening and Week 16
timeFrame: Measured at screening and Week 16
measure: The Conners' Continuous Performance Test (CPT) at Baseline, Weeks 4, 8, 12, and 16
timeFrame: Measured at screening; baseline; and Weeks 4, 8, 12, and 16
Secondary outcomes:
measure: The Range of Impaired Functioning Tool (LIFE-RIFT)
timeFrame: Baseline, Weeks 4, 8, 12, and 16
measure: Quality of Life Satisfaction Questionnaire (Q-LES-Q)
timeFrame: Screening
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai & Massachusetts General Hospital
name: Dan V. Iosifescu, MD
role: PRINCIPAL_INVESTIGATOR
References: