Efficacy and Safety of Galantamine for Improving Dysfunction in People With Bipolar Disorder

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Efficacy and Safety of Galantamine for Dysfunction in Bipolar Disorder

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Galantamine-ER
* Drug: Galantamine placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Galantamine-ER<br>Participants will receive treatment with extended release galantamine | Drug: Galantamine-ER<br>* Galantamine-ER 8 to 24 mg per day for 16 weeks<br>* Other names: Razadyne-ER;|
| Placebo Comparator: Galantamine placebo<br>Participants will receive treatment with placebo. | Drug: Galantamine placebo<br>* Galantamine placebo 8 to 24 mg per day for 16 weeks<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scores on the California Verbal Learning Test (CVLT-II) at Screening and Week 16 | CVLT is a test measuring verbal learning and verbal memory. Subjects are expected to remember a list of words. They are asked to repeat the words remembered 5 times (5 trials). Each of the words correctly remembered, in each trial, is marked as 1 point. The outcome measures presented are: CVLT Total Trials 1-5, Baseline = Number of total words remembered, sum of trials 1-5, at baseline CVLT Total Trials 1-5, Week 16 = Number of total words remembered, sum of trials 1-5, at week 16. | Measured at screening and Week 16 | 
| Scores on the Wisconsin Card Sorting Test (WCST) at Screening and Week 16 | WCST (Wisconsin Card Sorting Test) is a neuropsychological test measuring the ability to display flexibility in the face of changing schedules of reinforcement. Subjects are presented with cards and requested to match them. Unbeknownst to the subject, the matching rules change while the test is delivered. The test measures subjects' ability to understand the new rules. The outcome measures presented are Total correct baseline = total correct card choices at baseline Total errors baseline = total erroneous card choices at baseline Total correct week 16 = total correct card choices at week 16 Total errors baseline = total erroneous card choices at week 16 | Measured at screening and Week 16 | 
| The Conners' Continuous Performance Test (CPT) at Baseline, Weeks 4, 8, 12, and 16 | Conner's CPT (Conner's Continuous Performance Task) is a neuropsychological test that measures a person's sustained and selective attention. Subjects are instructed to click the space bar when they are presented with any letter except the letter X. The person must refrain from clicking if they see the letter X presented. Clicking to the letter X is a commission error, not clicking to other letters are omission errors. The outcome measures presented are Total number of errors = Total number of omission + commission errors This outcome measure is presented at each study visit (baseline, week 4, week 8, week 12, and week 16) | Measured at screening; baseline; and Weeks 4, 8, 12, and 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Range of Impaired Functioning Tool (LIFE-RIFT) | The LIFE-RIFT is a brief measure of functional impairment. The total scale score is a sum of four items with range of scale from 0 to 26 (from no impairment to severe impairment). | Baseline, Weeks 4, 8, 12, and 16 | 
| Quality of Life Satisfaction Questionnaire (Q-LES-Q) | The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is a self-report instrument designed to measure the degree of enjoyment and satisfaction experienced by subjects in various areas of daily functioning. There are 16 areas of functioning, each scored from 1 (very poor) to 5 (very good). The range of scores is 16-80, with lower scores representing lower functioning and satisfaction. The outcome measures presented are Q-LES-Q Total score = Sum of all scores from all 16 areas of functioning | Screening |