Use of Galantamine and CDP-choline (Citicoline) to Treat Adults With Schizophrenia (STAR-1)

This study has been completed.
Sponsor:
Collaborators:
Washington D.C. Veterans Affairs Medical Center
Information provided by (Responsible Party):
Stephen I. Deutsch, National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:
NCT00509067
First received: July 30, 2007
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention Phase
Schizophrenia
Drug: Galantamine
Drug: CDP-choline
Drug: Placebo
Drug: risperidone, olanzapine, quetiapine, ziprasidone, and/or aripiprazole
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Interventions to Test the Alpha7 Nicotinic Receptor Model in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Negative Symptoms Measured on Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Measured at Baseline and Weeks 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
    The score for each subject was the sum of the ratings for five items on the negative-symptom subscale of the PANSS: 1) blunted affect, 2) emotional withdrawal, 3) poor rapport, 4) passive/apathetic social withdrawal, and 5) lack of spontaneity and flow of conversation. Each item (symptom) is rated on a scale from 1 = absence of negative symptom to 7 = extreme negative symptom. The sum of the ratings for the five items range from 5 to 35, with higher scores indicating more severe symptoms. The primary outcome measure is the mean of the sum of these ratings across subjects.


Secondary Outcome Measures:
  • Clinical Global Impression [ Time Frame: Measured at Baseline and Weeks 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
  • Cognitive Measures (MATRICS: Attention, Memory, Processing Speed) [ Time Frame: Measured at Baseline and Weeks 8 and 16 ] [ Designated as safety issue: No ]
  • Nicotine Use [ Time Frame: Measured at Baseline and Weeks 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
  • Electrocardiogram [ Time Frame: Measured at pre- and post-intervention ] [ Designated as safety issue: Yes ]

Enrollment: 43
Study Start Date: November 2007
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Participants assigned to receive galantamine and CDP-choline
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.
Other Name: Razadyne
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: risperidone, olanzapine, quetiapine, ziprasidone, and/or aripiprazole
All participants will continue to take their regular regimen of risperidone, olanzapine, quetiapine, ziprasidone, and/or aripiprazole throughout the trial in addition to their assigned treatment.
Placebo Comparator: B
Participants assigned to receive placebo
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, olanzapine, quetiapine, ziprasidone, and/or aripiprazole
All participants will continue to take their regular regimen of risperidone, olanzapine, quetiapine, ziprasidone, and/or aripiprazole throughout the trial in addition to their assigned treatment.

Detailed Description:

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 16 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 15 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 14 weeks. Participants assigned to the control group will take two types of placebo pills every day for 16 weeks. All participants will continue to take their regular regimen of risperidone, olanzapine, quetiapine, ziprasidone, and/or aripiprazole 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.

CDP-choline and matching placebos were purchased from LifeLink Corporation. Galantamine and matching placebos were prepared and donated by Ortho McNeil Janssen Scientific Affairs LLC.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meets DSM-IV criteria for schizophrenia or schizoaffective disorder
  • Eligible for care within the Veterans Affairs Medical system
  • Taking risperidone, olanzapine, quetiapine, ziprasidone, and/or aripiprazole (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00509067

Locations
United States, District of Columbia
Washington Veterans Affairs Medical Center
Washington, District of Columbia, United States, 20422
Sponsors and Collaborators
Georgetown University
Washington D.C. Veterans Affairs Medical Center
Investigators
Principal Investigator: Stephen I. Deutsch, PhD, MD Washington Veterans Affairs Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Stephen I. Deutsch, Professor and Chair, Dept. of Psychiatry & Behavioral Sciences, Eastern Virginia Medical School, National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00509067     History of Changes
Other Study ID Numbers: R34 MH077849, R34MH077849, DATR A5-ETBD
Study First Received: July 30, 2007
Results First Received: July 1, 2013
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgetown University:
Schizoaffective Disorder
Acetylcholine
Nicotinic Receptors
Nicotine
Galantamine
negative symptoms

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Choline
Cytidine Diphosphate Choline
Galantamine
Risperidone
Quetiapine
Olanzapine
Aripiprazole
Ziprasidone
Lipotropic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Lipid Regulating Agents
Nootropic Agents
Central Nervous System Agents
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Cholinesterase Inhibitors
Enzyme Inhibitors
Cholinergic Agents
Neurotransmitter Agents
Serotonin Antagonists

ClinicalTrials.gov processed this record on July 22, 2014