Clinical trial NCT00573417: A Placebo-Controlled Trial of Modafinil (Provigil) Added to Clozapine in Patients With Schizophrenia
Official title: A Placebo-Controlled Trial of Modafinil (Provigil) Added to Clozapine in Patients With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Keywords: Schizophrenia
Clozapine
Cognition
Metabolic Syndrome
Negative Symptoms
Wakefulness
Fatigue
Lead sponsor: North Suffolk Mental Health Association
Sponsor class: OTHER
Collaborators: name: Cephalon
First posted: 2007-12-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate the effect size of modafinil compared to placebo upon cognitive functioning using a standard battery of cognitive tests.
timeFrame: 8 weeks
Secondary outcomes:
measure: Evaluate tolerability and safety of modafinil compared to placebo using the SAFTEE and vital signs.
timeFrame: 8 weeks
measure: 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).
timeFrame: 8 weeks
measure: Evaluate the effect size of modafinil compared to placebo upon negative symptoms using the SANS total score.
timeFrame: 8 Weeks
measure: Evaluate the effect size of modafinil compared to placebo upon weight, BMI, waist/hip circumference and fasting glucose and lipids.
timeFrame: 8 weeks
measure: Effect the variability of response in placebo and modafinil groups for each of the outcome measures.
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Freedom Trail Clinic
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Donald Goff, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Freudenreich O, Henderson DC, Macklin EA, Evins AE, Fan X, Cather C, Walsh JP, Goff DC. Modafinil for clozapine-treated schizophrenia patients: a double-blind, placebo-controlled pilot trial. J Clin Psychiatry. 2009 Dec;70(12):1674-80. doi: 10.4088/JCP.08m04683. Epub 2009 Aug 11.