A Proof of Concept Study of Intravenous Sodium Nitroprusside in Adults With Symptomatic Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: sodium nitroprusside; Placebo
Intervention description: intravenous; Placebo
Intervention MeSH terms: Nitroprusside
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        Inclusion Criteria:

        Each subject must meet all of the following criteria to be eligible for this study:

          1. Males or Females aged 18-65 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
             (DSM-IV-TR) criteria.

          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)
             Guidelines.

          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 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

          8. Understands and is able, willing, and (in the opinion of the investigator) likely to
             fully comply with the study procedures and restrictions.

        Exclusion Criteria

        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, confound the results of
             study, increase risk to the subject, or lead to difficulty complying with the
             protocol.

          4. Subjects on chlorpromazine, PDE-5 inhibitors, nitrites and any medication with CNS
             effects with the exception of antipsychotic drugs (other than chlorpromazine)
             anticholinergics, b-adrenergic antagonists, amantadine, biperiden, diphenhydramine,
             lorazepam, zolpidem, and temazepam.

          5. Medications which in the opinion of the PI, and in conjunction with the medical
             monitor, may be expected to significantly interfere with the metabolism or excretion
             of sodium nitroprusside, and/or may be associated with a significant drug interaction
             with sodium nitroprusside that may pose a significant risk to subjects' health and/or
             confound the study data.

          6. Pregnant or breast-feeding patients. Women of childbearing potential must have a
             negative pregnancy test performed at screening visit prior to randomization and prior
             to baseline at visits 3 and 6. Women enrolled in this trial must use adequate birth
             control.

          7. 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.

          8. Has tested positive for any of the following: cannabis, opioids, cocaine,
             amphetamines, barbiturates methadone, methamphetamine and phencyclidine at the
             screening or baseline visits. If positive, the urine drug toxicology screen may be
             repeated once based on investigator judgment, but due to safety concerns, the result
             must be negative for the subject to continue in the study.

          9. 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.

         10. Subjects that have taken an investigational drug or taken part in a clinical trial
             within 30 days prior to screening.

         11. Any other reason that, in the opinion of the investigator, would compromise patient
             safety or integrity of the study