Clinical Trial of Tolcapone for Cognition in Schizophrenia - Full Text View

Sponsored by:	National Institute of Mental Health (NIMH)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00044083

Purpose

This study will evaluate whether Atomoxetine improves cognition in healthy volunteers as well as patients with schizophrenia. Atomoxetine is a drug that has been FDA approved for Attention Deficit Disorder and allegedly increase the amount of the neurotransmitter dopamine in the frontal cortex of the brain.

Condition	Intervention	Phase
Schizophrenia	Drug: Tolcapone	Phase II

MedlinePlus related topics: Schizophrenia

Drug Information available for: Entacapone Dopamine Dopamine hydrochloride Riboflavin OR 611 Tolcapone

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Randomized, Double-Blind, Crossover Assignment, Efficacy Study
Official Title:	Randomized, Double-Blinded, Placebo Controlled Study of the Effects of Tolcapone and Entacapone on Cognitive Function in Patients With Schizophrenia and Normal Controls Based on COMT Genotype

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

Genetic differences in working memory testing or fMRI activation [ Designated as safety issue: No ]

Secondary Outcome Measures:

Panss, Ham-A, POMS, Blood draws for drug levels and liver enzymes [ Designated as safety issue: Yes ]

Estimated Enrollment:	210
Study Start Date:	August 2002

Intervention Details:

Tolcapone 200 mg tid: Placebo 1 week-Wash Out 1 week-Drug 1 week (or vice versa)

Detailed Description:

Psychopharmacological modulation of the catecholaminergic system can enhance some aspects of cognitive function. For example, COMT inhibitors can slightly improve working memory/executive function. Differences in the response between individuals might be related to a number of factors, including variations in the genes. The recent finding that a polymorphism in the catechol-o-methyl-transferase (COMT) gene, which produces a 4 fold change in enzyme activity, accounts for 4 percent of the variance in performance of working memory tasks in humans suggest that COMT genotype may predict response to COMT inhibitors. In the present proof of concept investigation our goal is to examine, in normal controls and patients with schizophrenia, the effect of a centrally acting (tolcapone) and of a peripherally acting (entacapone) COMT inhibitor on cognitive function. We predict that both normal controls and patients with schizophrenia with the val/val genotype will have a significant, though transient, improvement in working memory in subjects treated with tolcapone but not in those treated with entacapone. Furthermore, in conjunction with other NIMH imaging protocols, we would like to examine the neurophysiological correlates related to working memory. We predict, in tolcapone treated subjects, improved measures in prefrontal 'efficiency' in subjects and patients specifically with the val/val genotype. The present protocol will provide new insights on the importance of this genetic polymorphism in the regulation of aminergic-controlled cognitive function in normal individuals. Furthermore, this protocol will test whether COMT inhibitors offer a new treatment-based on genotype - for cognitive impairment in schizophrenia. No IND is required for the present study.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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:

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.
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.
Schizophrenic patients taking clozapine, a COMT inhibitor, any illicit drugs of abuse, or MAO inhibitors will be excluded.
Normal control subjects taking any medications other than occasional NSAI will be excluded.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00044083

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

More Information

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

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.

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.

Arnsten AF. Catecholamine regulation of the prefrontal cortex. J Psychopharmacol. 1997;11(2):151-62. Review.

Responsible Party:	National Institutes of Health ( Jose A. Apud, M.D./National Institute of Mental Health )
Study ID Numbers:	020239, 02-M-0239
Study First Received:	August 16, 2002
Last Updated:	October 6, 2008
ClinicalTrials.gov Identifier:	NCT00044083
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Catecholamines
Dopamine
Clinical Trial
fMRI
PFC
Vitamin B2
Riboflavin
Tolcapone

Placebo
Normal Volunteers
Schizophrenia
Healthy Volunteers
HV
Vitamin B2
Riboflavin

Study placed in the following topic categories:

Schizophrenia
Dopamine
Riboflavin
Mental Disorders
Tolcapone

Psychotic Disorders
Healthy
Schizophrenia and Disorders with Psychotic Features
Entacapone

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Therapeutic Uses
Antiparkinson Agents

Enzyme Inhibitors
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 30, 2009