Clinical Trial of Tolcapone for Cognition in Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00044083
Recruitment Status : Completed
First Posted : August 19, 2002
Last Update Posted : September 1, 2016
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief Summary:

This study will evaluate whether Tolcapone improves cognition in healthy volunteers as well as patients with schizophrenia. Talcapone 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 or disease Intervention/treatment Phase
Schizophrenia Drug: Tolcapone Phase 2

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 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 213 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
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
Study Start Date : August 2002
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Tolcapone

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

Primary Outcome Measures :
  1. Genetic differences in working memory testing or fMRI activation1

Secondary Outcome Measures :
  1. Panss, Ham-A, POMS, Blood draws for drug levels and liver enzymes

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

    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: 18-50 years.


  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00044083

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Principal Investigator: Jose A Apud, M.D. National Institute of Mental Health (NIMH)

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Institute of Mental Health (NIMH) Identifier: NCT00044083     History of Changes
Other Study ID Numbers: 020239
First Posted: August 19, 2002    Key Record Dates
Last Update Posted: September 1, 2016
Last Verified: June 2016

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
Clinical Trial
Vitamin B2
Normal Volunteers
Healthy Volunteers

Additional relevant MeSH terms:
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Antiparkinson Agents
Anti-Dyskinesia Agents
Catechol O-Methyltransferase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action