A Placebo-Controlled Single-Dose Trial of Sildenafil in Schizophrenia

Study Overview
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Brief Summary
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The study is a double-blind, placebo-controlled, random-order, single-dose crossover trial of sildenafil 50 & 100 mg added to stable antipsychotic treatment in schizophrenia patients to assess whether this PDE5 inhibitor improves cognitive functioning (including verbal memory, fluency, attention, spatial memory, motor speed, and executive function) and clinical symptoms (psychotic, negative, mood symptoms, and self-reports of side-effects).

Detailed Description
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Specific Aims: Evaluate the effects of single doses of sildenafil 50 & 100 mg compared to placebo on cognitive functioning, including verbal memory, fluency, attention, spatial memory, motor speed, and executive function. Evaluate the effects of single doses of sildenafil 50 & 100 mg compared to placebo on psychotic, negative, and mood symptoms. Assess self-reports of side effects of sildenafil 50 & 100 mg. Location and Subjects: 25 adult outpatients with schizophrenia will be recruited from the Massachusetts General Hospital outpatient clinic or the Freedom Trail Clinic of the Lindemann Center. All research procedures will be performed at the Psychopharmacology Clinic of the Massachusetts General Hospital. Subjects must be English speaking because the cognitive battery has only been validated in English.

Official Title
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A Placebo-Controlled Single-Dose Trial of Sildenafil in Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Sildenafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia, any subtype. Age 18-65 years Male or female Clinically stable without a medication change within 4 weeks Able to complete cognitive testing (must be English-speaking) Willing to use appropriate birth control during study participation (if female) Exclusion Criteria: Active substance abuse or dependence PDE 5 inhibitor taken within 24 hours of study drug Currently taking a drug that inhibits hepatic cytochrome P450 3A4 (eg. Nefazadone, fluvoxamine, erythromycin, ketoconazole, itraconazole, cimetidine, saquinavir, ritonavir, St. John's wort, or grapefruit juice). Currently taking drugs that induce P45 3A4 (eg. phenytoin, carbamezapine, Phenobarbital, rifampin) Unstable medical disease Significant cardiac disease Bleeding disorder Peptic ulcer disease Hepatic impairment Moderate or greater renal impairment History of migraines Currently taking nitrates or alpha blockers Resting blood pressure < 90/50 or >140/90 mm. History of intolerance to PDE5 inhibitors History of inappropriate sexual behavior (eg, masturbation in public, stalking, assault) History of priapism Pregnant or lactating

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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Sildenafil|1 capsule Sildenafil 50mg or Sildenafil 100mg or placebo taken at the time of study visit.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effects of single doses of sildenafil 50 & 100 mg compared to placebo on cognitive functioning, including verbal memory, fluency, attention, spatial memory, motor speed, and executive function. |  | 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effects of single doses of sildenafil 50 & 100 mg compared to placebo on psychotic, negative, and mood symptoms. |  | 12 days | 
| Side effects of sildenafil 50 & 100 mg as self-reported by subjects and as measured with vital signs. |  | 12 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Cognition, Sildenafil, PDE5 Inhibitor