Modafinil Augmentation Therapy for Excessive Daytime Sleepiness and Negative Symptoms in Patients With Schizophrenia

An Eight Week, Double-Blind, Placebo Controlled, Adjunctive Study of the Primary Effects of the Use of Flexible Doses of Modafinil 50mg to 200mg, on the Negative Symptoms, Cognition, and Excessive Daytime Sleepiness in Schizophrenic Patients

The purpose of this study is to test the effect of modafinil on the negative symptoms, such as blunted affect and social withdrawal, of schizophrenic patients and to determine modafinil's effect on excessive daytime sleepiness. A secondary purpose of the study is to examine the effect of modafinil on cognitive functioning of schizophrenic patients.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Modafinil

Detailed Description

Twenty six male patients with schizophrenia (twelve with Excessive Daytime Sleepiness and twelve without) will be enrolled at the San Diego Veterans Affairs Medical Center. Modafinil has been shown to increase alertness in individuals who are pathologically sleepy (Study C1538a/301/NAIUS).

Subjects will be randomized in a 1:1 ratio, stratified by excessive daytime sleepiness (value of >=9 on the Epworth Sleepiness Scale). Subjects will receive either modafinil or placebo, supplied by the sponsor. The study drug will be taken by mouth once daily in the morning. The titration schedule will be as follows:

1. The beginning does will be 50mg for 2 weeks
2. The study medication will be increased to 100mg at the week 2 study visit
3. The study medication will be increased to 200mg at the week 4 study visit and will continue for the remaining 4 weeks of the study. If subjects are unable to tolerate dosage increases, the dose will be decreased to the previous level.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161
      • VA Healthcare System, Department of Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Subjects must be able to communicate and give voluntary informed consent
• Subjects must be of the male gender
• Between the ages of 18 to 65 years.
• A diagnosis of Schizophrenia or Schizoaffective disorder as determined by DSM-IV criteria.
• Not conservatorized
• A negative symptom score on the PANSS of >= 20 and an MMSE score of >24
• No clinical evidence of a current unstable medical illness
• No current clinical evidence or past history of cerebral neurological impairment (including strokes, tumors or trauma leading to loss of consciousness)
• No history of drug or alcohol dependence in the past 2 years
• No evidence of drug or alcohol abuse in the past year, as determined by the DSM-IV criteria.
• No diagnosis of Narcolepsy as determined by DSM-IV criteria
• Must have an approved contact person for the duration of the study
• May be on a stable dose of SSRI for depressive symptoms
• No history of aggression

• No uncontrolled hypertension, as defined below (subjects cannot have any of the following):

  1. a new diagnosis of hypertension, or
  2. a change in antihypertensive medications in the past 30 days, or
  3. acute hypertension (systolic>160mmHg, diastolic>100mmHg)
• Maybe on a stable dose of a benzodiazepine
• The following medications will not be allowed during the study- methylphenidate, amphetamines, pemoline, zolpidem, MAO inhibitors, anticoagulant, TCA's, or barbiturates.
• Be on a stable does of an atypical neuroleptic
• May be on a stable does of an anticonvulsant for mood stabilization

Exclusion Criteria:

• Subjects cannot be female.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Adjunctive treatment with placebo	Drug: Placebo; Adjunctive treatment with placebo
Experimental: Modafinil; Treatment with titrated dose of study drug, modafinil.	Drug: Modafinil; Adjunctive treatment with titrated dose of modafinil; Other Names: Provigil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PANSS, and Sleep/wake activity measured using the Actillume (Ambulatory Monitoring, Inc.)	baseline, one month, two months

Secondary Outcome Measures

Outcome Measure	Time Frame
Neuropsychological Assessments that target cognitive abilities.	baseline, one month, two months

Collaborators and Investigators

• Sponsor: Veterans Medical Research Foundation
• Collaborators: Cephalon
• Investigators: Principal Investigator: James B Lohr, MD, PhD, Director, VA Center of Excellence for Stress and Mental Health (CESAMH)

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: October 17, 2007
• First Submitted That Met QC Criteria: October 17, 2007
• First Posted (Estimate): October 19, 2007

Study Record Updates

• Last Update Posted (Estimate): February 24, 2009
• Last Update Submitted That Met QC Criteria: February 20, 2009
• Last Verified: October 1, 2007

More Information

Terms related to this study

• Keywords: Excessive Daytime Sleepiness
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Disorders of Excessive Somnolence; Sleepiness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: C1538a-633