Clinical Trial of Tolcapone for Cognition in Schizophrenia
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia
Intervention: Tolcapone (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: National Institute of Mental Health (NIMH) Overall contact:
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov
Summary
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.
Clinical Details
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 design: Other, Randomized, Double-Blind, Crossover Assignment, Efficacy Study
Primary outcome: Genetic differences in working memory testing or fMRI activation
Secondary outcome: Panss, Ham-A, POMS, Blood draws for drug levels and liver enzymes
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
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
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.
Locations and Contacts
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting
Additional Information
NIH Clinical Center Detailed Web Page
Related 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.
Starting date: August 2002
Last updated: October 6, 2008
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