A Randomized Double-Blind, Placebo-Controlled, Proof of Concept Study of Intravenous Sodium Nitroprusside in Adults With Symptomatic Schizophrenia
Overview
- Phase
- Phase 2
- Intervention
- sodium nitroprusside
- Conditions
- Schizophrenia
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 60
- Locations
- 4
- Primary Endpoint
- Change in Positive and Negative Syndrome Scale (PANSS) - Total Score - Study Phases 1 and 2
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The primary objective of this study is to investigate whether a single infusion of intravenous sodium nitroprusside (0.5 μg/kg/min for 4 hours) is superior to placebo (5% dextrose solution) at in treating positive and negative symptoms of schizophrenia
Detailed Description
This is a phase II proof of concept (POC), multi-center, prospective, randomized, placebo-controlled, Sequential Parallel Comparison Design (SPCD) study, in which a total of 60 subjects with schizophrenia will be enrolled. The study will be conducted in two stages. The study treatment will be administered in a double-blind fashion for all subjects throughout both stages of the study. A total of 60 subjects with schizophrenia will be randomized in a 1:1:1 ratio to drug-drug sequence \[n=20; i.v. sodium nitroprusside (0.5 μg/kg/min for 4 hours) at week 0 and week 2\], placebo-drug sequence \[n=20; i.v. placebo at week 0 and i.v. sodium nitroprusside (0.5 μg/kg/min for 4 hours) at week 2\], and placebo-placebo sequence \[n=20; i.v. placebo at week 0 and again at week 2\]. The 4-week double-blind phase of treatment will be divided into two phases: Phase 1, from week 0 to week 2, and Phase 2 from week 2 to week 4. At the end of Phase 1 (week 2), the randomized subjects will be assessed and categorized into responders and non-responders, based on 20% or more reduction from baseline in their PANSS total score as per the evaluations at Randomization Visit (week 0). The data from the patients deemed placebo non-responders in phase 1 who go on to either stay on placebo or to receive treatment with sodium nitroprusside will be pooled with the data from Phase 1 from all subjects, according to SPCD.
Investigators
Maurizio Fava, MD
Director, Clinical Research Program
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Each subject must meet all of the following criteria to be eligible for this study:
- •Males or Females aged 18-65 years inclusive.
- •Primary diagnosis of Schizophrenia established by a structured psychiatric evaluation (SCID) based on Diagnostic and Statistical Manual of Mental Disorders Forth Edition (DSM-IV-TR) criteria.
- •Written informed consent in compliance with 21 CFR part 50 and in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines.
- •A Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1994) total score ≥ 70 with a score of \> 4 on two or more of the following PANSS items: delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content.
- •A score of ≥4 on the Clinical Global Impression-Severity (CGI-S) (Guy, 1976).
- •Confirmation of both diagnosis and severity of psychosis symptoms by an independent MGH SAFER interview.
- •Must have ongoing antipsychotic treatment for at least 8 weeks, with a stable dose for at least 4 weeks. Subjects who have failed to achieve clinically-recognized symptom reduction to at least 1 marketed antipsychotic agent, given at a Physician Desk Reference (PDR)-defined therapeutic dose for ≥ 8 weeks during the past 12 months, as assessed by the MGH FAST, will be eligible
- •Understands and is able, willing, and (in the opinion of the investigator) likely to fully comply with the study procedures and restrictions.
- •Exclusion Criteria
Exclusion Criteria
- Not provided
Arms & Interventions
Drug - Drug
Phase 1 - intravenous sodium nitroprusside Phase 2 - intravenous sodium nitroprusside
Intervention: sodium nitroprusside
Placebo - Drug
Phase 1 - intravenous dextrose Phase 2 - intravenous sodium nitroprusside
Intervention: sodium nitroprusside
Placebo - Placebo
Phase 1 - intravenous dextrose Phase 2 - intravenous dextrose
Intervention: Placebo
Outcomes
Primary Outcomes
Change in Positive and Negative Syndrome Scale (PANSS) - Total Score - Study Phases 1 and 2
Time Frame: For Phase 1, timeframe is Day 0 and Day 14; Phase 2 timeframe is Day 14 and Day 28
The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Total score minimum = 30, maximum = 210
Secondary Outcomes
- PANSS - Positive Subscale - Phases 1 and 2(Phase 1 timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28)
- PANSS - Negative Subscale - Phases 1 and 2(Phase 1 timeframe is Day 0 and Day 14; Phase 2 timeframe is Day 14 and Day 28)
- Average Percent Change From Baseline in the PANSS Total Score After 2 Weeks of Treatment Using SPCD(For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28)
- Percentage of Subjects With 20% or More Reduction From Baseline in PANSS Total Score After 2 Weeks of Treatment Using SPCD(For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28)
- Average Percent Change From Baseline in the PANSS Positive Subscale Score After 2 Weeks of Treatment Using SPCD(For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28)
- PANSS - General Psychopathology Subscale - Phases 1 and 2(Phase 1 timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28)
- Average Percent Change From Baseline in the PANSS General Psychopathology Subscale Score After 2 Weeks of Treatment Using SPCD(For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28)
- Average Percent Change From Baseline in the PANSS Negative Subscale Score After 2 Weeks of Treatment Using SPCD(For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28)