A Proof of Concept Study of Intravenous Sodium Nitroprusside in Adults With Symptomatic Schizophrenia
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
Study Start Date
Estimated Completion Date
- Drug: sodium nitroprusside
- Other: Placebo
- Internal Medicine: Clinical Pharmacology,Psychiatry
- Psychiatry : Neuro/Psych Pharmacol,Schizophrenia/Psychosis
- Family Medicine: Clinical Pharmacology,Psychiatry
- Pharmacy: Neuro/Psych pharmacology
- Mental Disorders
Massachusetts General Hospital -- 2014P001204
Massachusetts General Hospital
Each subject must meet all of the following criteria to be eligible for this study:
1. Males or Females aged 18-55 years inclusive.
2. Primary diagnosis of Schizophrenia established by a structured psychiatric evaluation
(SCID) based on Diagnostic and Statistical Manual of Mental Disorders Forth Edition
3. Written informed consent in compliance with 21 CFR part 50 and in accordance with the
International Conference on Harmonization (ICH) Good Clinical Practice (GCP)
4. 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.
5. A score of ?4 on the Clinical Global Impression—Severity (CGI-S) (Guy, 1976).
6. Confirmation of both diagnosis and severity of psychosis symptoms by an independent
MGH SAFER interview.
7. Must have ongoing antipsychotic treatment for at least 8 weeks, with a stable dose
for at least 4 weeks. Subjects refractory to antipsychotic treatment, defined as
failure to achieve clinically-recognized symptom reduction) to ? 2 marketed
antipsychotic agents, given at a Physician Desk Reference (PDR)-defined therapeutic
dose for ? 8weeks over the prior 12 months, as assessed by the MGH FAST will be
8. Understands and is able, willing, and (in the opinion of the investigator) likely to
fully comply with the study procedures and restrictions.
Subjects who meet any of the following criteria will be excluded from the study.
1. Subjects with a history of renal insufficiency, congestive heart failure, cardiac
arrhythmias or history of myocardial infarction.
2. Subjects with a history of symptomatic orthostatic hypotension defined as sitting to
standing systolic blood pressure < 90mmHg or diastolic blood pressure < 60mm Hg with
any of the following symptoms: lightheaded or dizzy upon standing, blurry
vision,weakness,fainting (syncope),confusion, or nausea.
3. Subjects with any clinically significant abnormalities as determined by medical
history, physical exam, clinical and lab evaluation suggestive of an underlying
disease state that may, in the opinion of the investigator, may confound the results
of study, increase risk to the subject or lead to difficulty complying with the
4. Subjects on clorpromazine, PDE-5 inhibitors, nitrites and any medication with CNS
effects excluding, patients on antipsychotic drugs, anticholinergics, b-adrenergic
antagonists, amantadine, biperiden, diphenhydramine, lorazepam, zolpidem, and
5. Pregnant or breast-feeding patients. Women of childbearing potential must have a
negative pregnancy test performed at baseline visit prior to randomization. Women
enrolled in this trial must use adequate birth control.
6. Subjects with a current (within the last 3 months) DSM-IV-TR diagnosis of alcohol or
substance use disorder or dependence (excluding nicotine) as established by the
clinical assessment (SCID) at the screening visit will be excluded.
7. Subjects at imminent risk of suicide or injury to self or others, as per the opinion
of the investigator, or history of significant suicide attempt within the last 6
months as per C-SSRS.
8. Subjects that have taken an investigational drug or taken part in a clinical trial
within 30 days prior to screening.
9. Any other reason that, in the opinion of the investigator, would compromise patient
safety or integrity of the study
18 Years to 55 Years
Accepts Healthy Volunteers
Study Locations and Contact Information (4)
|Zucker Hillside Hospital - Glen Oaks, New York||40.7 miles||Jennifer Alexander BA||718-470-8442||jalexande5@NSHS.edu|
|New York University Langone Medical CenterBellevue Hospital - New York, New York||50.2 miles||Helen Tan BA||646-754-4810||Helen.Tan@nyumc.org|
|University of Massachusetts Medical School - Worcester, Massachusetts||105.6 miles||Domenico Lombardi BA||508-856-2505||Domenico.Lombardi@umassmed.edu|
|Schizophrenia Clinical Research Program Massachusetts General Hospital - Boston, Massachusetts||137.9 miles||Chris McCain BA||617-912-7864||CMCCAIN@mgh.harvard.edu|