Protocol Number: 02-M-0239

Title:

Randomized, Double-Blinded, Placebo Controlled Study Of The Effects Of Tolcapone On Cognitive Function In Patients With Schizophrenia And Normal Controls Based On COMT Genotype

Number:

02-M-0239

Summary:

The purpose of this study is to test whether the drug tolcapone improves the memory of patients with schizophrenia.

The catecholaminergic system can enhance some aspects of cognitive function, such as working memory. Studies suggest that drugs that inhibit COMT may improve working memory and executive function. However, individuals differ in their response to COMT inhibitors. These response differences may be related to genotypic variations in COMT. This study will examine the effect of tolcapone, a COMT inhibitor, on the cognitive function of people with schizophrenia, compared to healthy volunteers.

Participants with schizophrenia will be admitted to the NIH Clinical Center for 4 to 12 weeks during their participation in the study. Healthy volunteers will participate as outpatients. During Week 1 of the study, participants will receive either tolcapone or a placebo (an inactive pill) three times a day for 7 days. Participants will not receive tolcapone or placebo in Week 2. During Week 3, medications will be crossed over in all participants (those given placebo during week 1 will receive tolcapone, and vice versa). Participants will undergo psychological testing, blood tests, and a magnetic resonance imaging (MRI) scan of the brain.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

1) Prior participation under NIH protocol number 95-M-0150, or new normal volunteers or schizophrenic patients that meet criteria for NIH protocol number 95-M-0150.

2) No Axis I or Axis II diagnosis in normal volunteers.

3) Age range: 18-60 years.

EXCLUSION CRITERIA:

1) Normal volunteers with an Axis I or Axis II disorder obtained either from prior SCID interview in Protocol 95-M-0150 or through a screening interview will be excluded.

2) Subjects with a history of cardiovascular disease, liver disease and other medical illnesses, and untreated or uncontrolled hypertension will be excluded. An electrocardiogram, blood pressure, pulse rate and metabolic panel including, LFTs will be checked on all subjects prior to participation in the study. Individuals with persistent tardive dyskinesia or abnormal LFTs, or individuals with significant history of alcoholism or liver enzyme elevation will be excluded from the study.

3) Schizophrenic patients taking clozapine, a COMT inhibitor, any illicit drugs of abuse, or MAO inhibitors will be excluded.

4) Normal control subjects taking any medications other than occasional NSAI will be excluded.

5) Pregnant women. Women of childbearing potential will undergo a urine pregnancy test the day the study initiates and screened by history for the possibility of pregnancy.

Special Instructions: Currently Not Provided

Keywords:

Catecholamines

Dopamine

Clinical Trial

fMRI

PFC

Vitamin B2

Riboflavin

Tolcapone

Placebo

Recruitment Keywords:

Schizophrenia

Healthy Volunteers

HV

Vitamin B2

Riboflavin

Conditions:

Schizophrenia

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Aksoy S, Klener J, Weinshilboum RM. Catechol O-methyltransferase pharmacogenetics: photoaffinity labelling and western blot analysis of human liver samples. Pharmacogenetics. 1993 Apr;3(2):116-22. PMID: 8518836

Andreasen NC, Arndt S, Cizadlo T, O'Leary DS, Watkins GL, Ponto LL, Hichwa RD. Sample size and statistical power in [15O]H2O studies of human cognition. J Cereb Blood Flow Metab. 1996 Sep;16(5):804-16. PMID: 8784225

Arnsten AF. Catecholamine regulation of the prefrontal cortex.

J Psychopharmacol. 1997;11(2):151-62. Review. PMID: 9208378

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