Effects of Modafinil on Brain Function in Patients With Schizophrenia

This study is currently recruiting participants.
Verified February 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00057707
First received: April 5, 2003
Last updated: March 14, 2014
Last verified: February 2014

April 5, 2003
March 14, 2014
March 2003
December 2014   (final data collection date for primary outcome measure)
Genetic differences in working memory testing or fMRI activation [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00057707 on ClinicalTrials.gov Archive Site
Panss, Ham-A, Blood draws for drug levels and liver enzymes [ Designated as safety issue: No ]
Not Provided
Not Provided
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Effects of Modafinil on Brain Function in Patients With Schizophrenia
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

This study will evaluate whether modafinil improves cognition in patients with schizophrenia and healthy volunteers. Modafinil is a drug that has been FDA approved for day-time sleepiness and allegedly increase the amount of the neurotransmitter dopamine in the frontal cortex of the brain

Psychopharmacological modulation of the catecholaminergic system can enhance some aspects of cognitive function. For example, COMT inhibitors can slightly improve working memory/executive function. Similarly, modafinil, a catecholaminergic agonist that increases extracellular dopamine in the prefrontal cortex was also shown to improve delay-dependent working memory. 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% of the variance in performance of working memory tasks in humans suggest that COMT genotype may predict response to COMT inhibitors or to other agonists that increase catecholaminergic function in the frontal cortex.

In the present investigation our goal is to examine, in normal controls and patients with schizophrenia, the effect of modafinil, a drug that increases DA output in the frontal cortex, on cognitive function and brain physiology. We predict that both normal controls and patients with schizophrenia with the val/val genotype will have a significant improvement in working memory compared with individuals possessing other genotypes. Furthermore, in conjunction with other NIMH imaging protocols, we predict that modafinil will produce a similar genotype-dependent effect on the neurophysiological correlates related to working memory assayed with fMRI. 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 modafinil offers a new treatment -based on genotype - for cognitive impairment in schizophrenia. The FDA granted a waiver for the use of Modafinil in this study.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
  • Schizophrenia
  • Schizoaffective Disorder
  • Drug: Modafinil
    Placebo 1 week-Wash out 1 week - Drug 1 week (or vice versa)
  • Procedure: Functional MRI
    N/A
  • Procedure: Neuropsychological Testing
    N/A
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
210
December 2014
December 2014   (final data collection date for primary outcome measure)
  • 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: 18-50 years.

EXCLUSION CRITERIA:

Subjects with a history of cardiovascular disease, liver disease and other medical illnesses, current active substance abuse or history of substance abuse for more than 5 years, and untreated or uncontrolled hypertension will be excluded. Individuals with persistent tardive dyskinesia 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, buproprion, stimulants, other cognitive enhancers or 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)

Both
18 Years to 50 Years
Yes
Contact: Jose A Apud, M.D. (301) 594-6561 apudj@mail.nih.gov
United States
 
NCT00057707
030143, 03-M-0143
Not Provided
Not Provided
National Institute of Mental Health (NIMH)
Not Provided
Principal Investigator: Jose A Apud, M.D. National Institute of Mental Health (NIMH)
National Institutes of Health Clinical Center (CC)
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP