Official Title: “Interventions to Test the Alpha7 Nicotinic Receptor Model in Schizophrenia”

This study will evaluate the effectiveness of galantamine and CDP-choline in improving symptoms associated with schizophrenia.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2010

Schizophrenia is a life-long brain disorder affecting approximately 1 percent of Americans each year. Schizophrenia can be extremely disabling, causing people to hear voices, experience paranoia or hallucinations, believe that others are controlling their thoughts, and even fail at maintaining a job or caring for themselves. Current medications help to relieve most of these negative symptoms, but not all. Many people with schizophrenia still suffer from low energy levels, an inability to concentrate, and memory loss. Galantamine is a medication that is used to improve memory and energy levels in people with Alzheimer's disease, and CDP-choline is a nutritional supplement. The purpose of this study is to evaluate the effectiveness of adding galantamine and CDP-choline to a stable anti-psychotic medication regimen of risperidone as a way of improving symptoms in adults with schizophrenia.

Participants in this double-blind study will attend an initial screening during which they will undergo a physical exam, an electrocardiogram, and blood and urine collection.

Participants will then be randomly assigned to receive galantamine and CDP-choline or a placebo treatment for 17 weeks. Participants assigned to the treatment group will take 500 mg of CDP-choline daily for the first 3 days, 1,000 mg daily for the next 4 days, and 2,000 mg daily for the following 16 weeks. Participants assigned to the treatment group will also take 8 mg of galantamine daily for the first week, 16 mg daily for the next week, and 24 mg daily for the following 15 weeks. Participants assigned to the control group will take two placebo pills every day for 17 weeks. All participants will continue to take their regular regimen of risperidone throughout the trial in addition to their assigned treatment. Staff members will meet with participants during the first week of the study and every 4 weeks afterward until study completion. During these meetings, participants will identify any side effects, report nicotine intake, breathe into a machine that measures the amount of nicotine in the body, and complete written and computerized tasks on concentration and memory. Each meeting may last up to 3 hours. On the last week of the study, blood and urine samples will be collected and an electrocardiogram will be administered. Results from this study will be used to evaluate whether CDP-choline and galantamine improve schizophrenia symptoms.

Intervention(s) in this Clinical Trial

• Drug: Galantamine
  • Galantamine will be titrated to 24 mg/day over 2 weeks. Participants will receive 8 mg/day in two divided doses for 1 week, 16 mg/day in two divided doses for 1 week, and 24 mg/day in two divided doses beginning in Week 3. They will be maintained on 24 mg/day for the remainder of the study.
• Drug: CDP-choline
  • CDP-choline will serve as the dietary source of choline. CDP-choline will be titrated to 2000 mg/day over 1 week. Subjects will receive 500 mg/day for 3 days; Thereafter, the dose of CDP-choline will be increased to 1,000 mg/day in two divided doses for 4 days. At the beginning of Week 2, participants will receive the maximum fixed dose of 2000 mg/day in two divided doses, which will be held constant through the end of Week 16.
• Drug: Placebo
  • The schedule of dose titration of placebo galantamine and placebo CDP-choline will follow the schedule of active medication condition using matching placebos for each agent.
• Drug: Risperidone
  • All participants will continue to take their regular regimen of risperidone throughout the trial in addition to their assigned treatment.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Participants assigned to receive galantamine and CDP-choline
• Placebo Comparator: B
  • Participants assigned to receive placebo

Primary Measures

• Negative symptoms measured on Positive and Negative Syndrome Scale
  • Time Frame: Measured at Baseline and Weeks 4, 8, 12, and 16
    Safety Issue?: No

Secondary Measures

• Clinical Global Impression
  • Time Frame: Measured at Baseline and Weeks 4, 8, 12, and 16
    Safety Issue?: No
• Cognitive measures (MATRICS: attention, memory, processing speed)
  • Time Frame: Measured at Baseline and Weeks 8 and 16
    Safety Issue?: No
• Nicotine use
  • Time Frame: Measured at Baseline and Weeks 4, 8, 12, and 16
    Safety Issue?: No
• Electrocardiogram
  • Time Frame: Measured at pre- and post-intervention
    Safety Issue?: Yes

Inclusion Criteria:

• Meets DSM-IV criteria for schizophrenia or schizoaffective disorder
• Eligible for care within the Veterans Affairs Medical system
• Taking risperidone (oral or injection)

Exclusion Criteria:

• Significant liver, kidney, lung, endocrine, active peptic ulcer, or cardiovascular disease
• Seizure disorder and/or head injury
• Substance use or abuse within 3 months of study entry
• Pregnant

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

Stephen I. Deutsch, PhD, MD Principal Investigator Washington Veterans Affairs Medical Center  

Overall Contact: Stephanie M Rosse, BS 202-745-8000 Stephanie.Rosse@va.gov

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00509067

Study ID Number: 1 R34 MH077849

ClinicalTrials.gov Identifier: NCT00509067

Health Authority: United States: Food and Drug Administration