Protocol Number: 03-M-0143

Title:

Randomized, Double-Blinded, Placebo Controlled Study of the Effects of Modafinil on Cognitive Function in Patients With Schizophrenia and Normal Controls Based on COMT Genotype

Number:

03-M-0143

Summary:

The purpose of this study is to test the effect of the drug modafinil on brain functioning in individuals with schizophrenia and in healthy volunteers.

Drug-induced changes in the catecholaminergic system can enhance some aspects of cognitive functions. Catechol-O-methyl-transferase (COMT) inhibitors can improve working memory and executive functioning, and catecholaminergic agonists such as modafinil can improve delay-dependent working memory. Patients differ in their responses to drugs affecting the catecholaminergic system. These response differences may be related to multiple factors, including gene variation. Polymorphism in the COMT gene accounts for 4% of the variance in performance of working memory tasks, suggesting that COMT genotype may predict response to drugs such as modafinil.

Participants in this study will be screened with a physical examination, laboratory tests, and an electrocardiogram (EKG). Women of reproductive potential will have a pregnancy test. The comparison group of healthy volunteers will participate as outpatients; participants with schizophrenia will be admitted to the NIH Clinical Center for up to 12 weeks and will continue to take any necessary medications during this time. Participants will receive either modafinil or placebo (an inactive pill) once a day for the first week of the study. During Week 2, participants will not receive any medication. During Week 3, medications will be crossed over in all participants (those given placebo in week 1 will receive modafinil, and vice versa). Participants will undergo blood collections, psychological 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): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Prior participation under NIH protocol # 95-M-0150, or new normal volunteers. Patients with Schizophrenia or Schizoaffective disorder that meet criteria for NIH protocol # 95-M-0150 will be included.

No active Axis I or Axis II diagnosis in normal volunteers.

Age range: 18-60 years.

EXCLUSION CRITERIA:

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

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

Normal control subjects taking any medications affecting brain function will be excluded.

Pregnant or breastfeeding 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.

Patients with significant history of violence against self or others as established in protocol # 89-M-0160 (Inpatient evaluation of neuropsychiatric patients)

Special Instructions: Currently Not Provided

Keywords:

Catecholamines

Dopamine

fMRI

Working Memory

Clinical Trial

Stabilization

Inpatients

Placebo

Modafinil

Recruitment Keywords:

Schizophrenia

Schizoaffective Disorder

Healthy Volunteer

HV

Conditions:

Schizophrenia

Schizoaffective Disorder

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:

Aguirre JA, Cintra A, Hillion J, Narvaez JA, Jansson A, Antonelli T, Ferraro L, Rambert FA, Fuxe K. A stereological study on the neuroprotective actions of acute modafinil treatment on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigral lesions of the male black mouse. Neurosci Lett. 1999 Nov 19;275(3):215-8.

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.

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Bethesda, Maryland 20892. Last update: 10/16/2004