Clinical trial NCT00509067: Use of Galantamine and CDP-choline (Citicoline) to Treat Adults With Schizophrenia
Official title: Interventions to Test the Alpha7 Nicotinic Receptor Model in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Schizoaffective Disorder
Acetylcholine
Nicotinic Receptors
Nicotine
Galantamine
negative symptoms
Lead sponsor: Georgetown University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Washington D.C. Veterans Affairs Medical Center
First posted: 2007-07-31
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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

Primary outcomes:
measure: Negative Symptoms Measured on Positive and Negative Syndrome Scale (PANSS)
timeFrame: Measured at Baseline and Weeks 4, 8, 12, and 16
Secondary outcomes:
measure: Clinical Global Impression
timeFrame: Measured at Baseline and Weeks 4, 8, 12, and 16
measure: MATRICS Verbal Learning and Memory
timeFrame: Measured at Baseline and Weeks 8 and 16
Other outcomes:
Locations:
city: Washington
country: United States
facility: Washington Veterans Affairs Medical Center
state: District of Columbia
Study officials:
affiliation: Washington Veterans Affairs Medical Center
name: Stephen I. Deutsch, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Deutsch SI, Schwartz BL, Schooler NR, Rosse RB, Mastropaolo J, Gaskins B. First administration of cytidine diphosphocholine and galantamine in schizophrenia: a sustained alpha7 nicotinic agonist strategy. Clin Neuropharmacol. 2008 Jan-Feb;31(1):34-9. doi: 10.1097/wnf.0b013e31806462ba.
citation: Deutsch SI, Rosse RB, Schwartz BL, Schooler NR, Gaskins BL, Long KD, Mastropaolo J. Effects of CDP-choline and the combination of CDP-choline and galantamine differ in an animal model of schizophrenia: development of a selective alpha7 nicotinic acetylcholine receptor agonist strategy. Eur Neuropsychopharmacol. 2008 Feb;18(2):147-51. doi: 10.1016/j.euroneuro.2007.05.008. Epub 2007 Jul 26.
citation: Martin LF, Freedman R. Schizophrenia and the alpha7 nicotinic acetylcholine receptor. Int Rev Neurobiol. 2007;78:225-46. doi: 10.1016/S0074-7742(06)78008-4.
citation: Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, Ellis J, Zerbe GO, Leonard S, Stevens KE, Stevens JO, Martin L, Adler LE, Soti F, Kem WR, Freedman R. Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry. 2006 Jun;63(6):630-8. doi: 10.1001/archpsyc.63.6.630.