Effects of Modafinil on Brain Function in Patients With Schizophrenia

December 6, 2019 updated by: National Institute of Mental Health (NIMH)

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

...

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

176

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Genetic differences in working memory testing or fMRI activation

Secondary Outcome Measures

Outcome Measure
Panss, Ham-A, Blood draws for drug levels and liver enzymes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Jose A Apud, M.D., National Institute of Mental Health (NIMH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 26, 2003

Primary Completion (Actual)

June 16, 2017

Study Completion (Actual)

June 16, 2017

Study Registration Dates

First Submitted

April 5, 2003

First Submitted That Met QC Criteria

April 4, 2003

First Posted (Estimate)

April 7, 2003

Study Record Updates

Last Update Posted (Actual)

December 9, 2019

Last Update Submitted That Met QC Criteria

December 6, 2019

Last Verified

June 16, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 030143
  • 03-M-0143

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Schizophrenia

Clinical Trials on Modafinil

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovenia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe