A Placebo-Controlled Trial of Modafinil (Provigil) Added to Clozapine in Patients With Schizophrenia

Phase 4

Completed

Brief Summary: This pilot study is an eight-week, randomized, double-blind, placebo-controlled, escalating dose trial of the novel vigilance-promoting drug, modafinil, added to a stable dose of clozapine in 40 patients with schizophrenia or schizoaffective disorder. Modafinil will be initiated at 100 mg/d. After 2 weeks, the study drug may be increased to 200 mg/d and after 4 weeks, study drug may be increased to a maximum of 300 mg/d. Dose escalation will be based upon persistence of sedation versus emergence of side effects.

Detailed Description: This pilot study is an eight-week, randomized, double-blind, placebo-controlled, escalating dose trial of the novel vigilance-promoting drug, modafinil, added to a stable dose of clozapine in 40 patients with schizophrenia or schizoaffective disorder. Modafinil will be initiated at 100 mg/d. After 2 weeks, the study drug may be increased to 200 mg/d and after 4 weeks, study drug may be increased to a maximum of 300 mg/d. Dose escalation will be based upon persistence of sedation versus emergence of side effects.

1. Evaluate tolerability and safety of modafinil compared to placebo using the SAFTEE and vital signs.

2. Evaluate the effect size of modafinil compared to placebo upon wakefulness and fatigue using the Epworth Sleepiness Scale (ESS) and the Fatigue Severity Scale (FSS).

3. Evaluate the effect size of modafinil compared to placebo upon negative symptoms using the SANS total score.

4. Evaluate the effect size of modafinil compared to placebo upon cognitive functioning using a standard battery of cognitive tests.

5. Evaluate the effect size of modafinil compared to placebo upon weight, BMI, waist/hip circumference and fasting glucose and lipids.

6. Effect the variability of response in placebo and modafinil groups for each of the outcome measures.

Recruitment & Eligibility

Inclusion Criteria

Diagnosis of Schizophrenia, any subtype or schizoaffective disorder
Ages 18-65 years
Capable of providing informed consent, or capable of providing assent with a guardian who provides informed consent
Stable dose of clozapine for at least 1 month
Three months of stable psychotic symptoms

Exclusion Criteria

Serious medical or neurological illness (unstable cardiac disease, seizure disorder, malignancy, liver or renal impairment, etc.)
Current substance abuse
Pregnancy, nursing, or unwilling to use appropriate birth control measures during participation if female and fertile.
Unable to complete neuropsychological tests
History of serious blood dyscrasia requiring discontinuation of clozapine
Serious suicidal or homicidal risk within the past six months
Current treatment with a psychostimulant

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	placebo
modafinil	modafinil	modafinil 100mg, 200mg, or 300mg (dose escalation)

Primary Outcome Measures

Name	Time	Method
Evaluate the effect size of modafinil compared to placebo upon cognitive functioning using a standard battery of cognitive tests.	8 weeks

Secondary Outcome Measures

Name	Time	Method
Effect the variability of response in placebo and modafinil groups for each of the outcome measures.	8 weeks
Evaluate tolerability and safety of modafinil compared to placebo using the SAFTEE and vital signs.	8 weeks
Evaluate the effect size of modafinil compared to placebo upon wakefulness and fatigue using the Epworth Sleepiness Scale (ESS) and the Fatigue Severity Scale (FSS).	8 weeks
Evaluate the effect size of modafinil compared to placebo upon negative symptoms using the SANS total score.	8 Weeks
Evaluate the effect size of modafinil compared to placebo upon weight, BMI, waist/hip circumference and fasting glucose and lipids.	8 weeks

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