Clinical Trial of Tolcapone for Cognition in Schizophrenia
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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.
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| Condition | Intervention | Phase |
|---|---|---|
|
Schizophrenia |
Drug: Tolcapone |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double-Blind |
| 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 |
- Genetic differences in working memory testing or fMRI activation1 [ Designated as safety issue: No ]
- Panss, Ham-A, POMS, Blood draws for drug levels and liver enzymes [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 240 |
| Study Start Date: | August 2002 |
| Estimated Study Completion Date: | November 2013 |
| Estimated Primary Completion Date: | November 2013 (Final data collection date for primary outcome measure) |
-
Drug: Tolcapone
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.
Eligibility| Ages Eligible for Study: | 18 Years to 50 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
INCLUSION CRITERIA:
- 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.
- No Axis I or Axis II diagnosis in normal volunteers.
- Age range: 18-50 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| Contact: Joann Berkson, R.N. | (301) 451-0167 | |
| Contact: Jose A Apud, M.D. | (301) 594-6561 | apudj@mail.nih.gov |
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
| Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 prpl@mail.cc.nih.gov | |
| Principal Investigator: | Jose A Apud, M.D. | National Institute of Mental Health (NIMH) |
More Information
Additional Information:
Publications:
| Responsible Party: | National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ) |
| ClinicalTrials.gov Identifier: | NCT00044083 History of Changes |
| Other Study ID Numbers: | 020239, 02-M-0239 |
| Study First Received: | August 16, 2002 |
| Last Updated: | February 7, 2013 |
| 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 |
Additional relevant MeSH terms:
|
Schizophrenia Schizophrenia and Disorders with Psychotic Features Mental Disorders Tolcapone Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
Pharmacologic Actions Antiparkinson Agents Anti-Dyskinesia Agents Central Nervous System Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on June 17, 2013