Effects of Modafinil on Brain Function in Patients With Schizophrenia

This study is currently recruiting participants. (see Contacts and Locations)
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
  Purpose

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


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: Modafinil
Procedure: Functional MRI
Procedure: Neuropsychological Testing
Phase 1

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 Modafinil on Cognitive Function in Patients With Schizophrenia and Normal Controls Based on COMT Genotype

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Genetic differences in working memory testing or fMRI activation [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Panss, Ham-A, Blood draws for drug levels and liver enzymes [ Designated as safety issue: No ]

Estimated Enrollment: 210
Study Start Date: March 2003
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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: 18-50 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)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00057707

Contacts
Contact: Jose A Apud, M.D. (301) 594-6561 apudj@mail.nih.gov

Locations
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   
Sponsors and Collaborators
Investigators
Principal Investigator: Jose A Apud, M.D. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00057707     History of Changes
Other Study ID Numbers: 030143, 03-M-0143
Study First Received: April 5, 2003
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Catecholamines
Dopamine
fMRI
Working Memory
Clinical Trial
Stabilization
Inpatients
Placebo
Modafinil
Normal Volunteers
Schizophrenia
Schizoaffective Disorder
Healthy Volunteer
HV

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Armodafinil
Modafinil
Central Nervous System Agents
Central Nervous System Stimulants
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Wakefulness-Promoting Agents

ClinicalTrials.gov processed this record on October 22, 2014