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

Study Overview
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Brief Summary
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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
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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. Evaluate tolerability and safety of modafinil compared to placebo using the SAFTEE and vital signs. 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). Evaluate the effect size of modafinil compared to placebo upon negative symptoms using the SANS total score. Evaluate the effect size of modafinil compared to placebo upon cognitive functioning using a standard battery of cognitive tests. Evaluate the effect size of modafinil compared to placebo upon weight, BMI, waist/hip circumference and fasting glucose and lipids. Effect the variability of response in placebo and modafinil groups for each of the outcome measures.

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

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: modafinil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: modafinil<br>modafinil 100mg, 200mg, or 300mg (dose escalation) | Drug: modafinil<br>* modafinil 100mg tablets. dose excalation up to 300mg<br>* Other names: Provigil;|
| Placebo Comparator: placebo<br>placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effect size of modafinil compared to placebo upon cognitive functioning using a standard battery of cognitive tests. |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Effect the variability of response in placebo and modafinil groups for each of the outcome measures. |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Clozapine, Cognition, Metabolic Syndrome, Negative Symptoms, Wakefulness, Fatigue