The Effect of Nitric Oxide on Spatial Working Memory in Patients With Schizophrenia - Pilot Study

Phase 1

Completed

• Conditions: Schizophrenia
• Interventions: Other: Placebo; Drug: Sodium Nitroprusside infusion

• Registration Number: NCT02176044
• Lead Sponsor: King's College London

Brief Summary

Spatial working memory (ability to remember where objects are in space) is impaired in patients with schizophrenia. It is thought that this impairment occurs due to problems with the chemical messenger (neurotransmitter), glutamate, and the N-methyl-D-aspartate (NMDA) glutamate receptor, particularly in the hippocampal brain region. NMDA receptor activation leads to increases in the release of the second messenger Nitric Oxide. Impaired NMDA receptor function would therefore be predicted to lead to reductions in Nitric Oxide production. Recent work suggests that a drug, sodium nitroprusside, which releases nitric oxide, enhances some aspects of cognition in schizophrenia (specifically related to negative symptoms). In this study, the investigators will test the hypothesis that sodium nitroprusside improves spatial working memory in patients with schizophrenia. 15 patients will receive sodium nitroprusside, and 15 will receive a nonactive compound (placebo). Their performance on a spatial working memory task will be tested before and after administration of sodium nitroprusside or placebo.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-06-25
• Study First Submitted QC: 2014-06-25
• Study First Posted: 2014-06-26
• Study Start: 2014-08
• Primary Completion: 2016-02
• Study Completion: 2016-02
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-08
• Last Update Posted: 2016-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Patients with a diagnosis of schizophrenia or schizoaffective disorder, currently experiencing an exacerbation of symptoms (a score > 20 for PANSS-Positive subscale), currently taking antipsychotics and who have given informed consent to participate.

Exclusion Criteria

History of hypertension or current resting systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg. Relevant medical illness (renal, hepatic, cardiac), prior history of intolerance to sodium nitroprusside, presence of a seizure disorder, any change in psychotropic medication in previous 6 weeks, diagnosis of substance abuse, pregnancy (as determined by urine test) or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Glucose infusion	Placebo	Placebo infusion of sterile 5% glucose - 500ml infused over 4 hours.
Sodium Nitroprusside infusion	Sodium Nitroprusside infusion	Sodium nitroprusside dissolved in 5% glucose solution. Infused at 0.5mcg/kg/min for 4 hours.

Primary Outcome Measures

Name	Time	Method
Spatial Working Memory	4 hours post-infusion	performance on Cambridge Neuropsychological Test Automated Battery spatial working memory task

Secondary Outcome Measures

Name	Time	Method
Blood pressure	4 hours post-infusion	Measurement of blood pressure.
Positive and Negative Syndrome Scale (PANSS)	4 hours post-infusion	Symptoms rated on PANSS
Brief Psychiatric Rating Scale (BPRS)	4 hours post-infusion	Symptoms rated on BPRS
Quick Inventory of Depressive Symptomatology (QIDS)	4 hours post-infusion	Symptoms rated on QIDS
Hypomania Checklist (HCL-32)	4 hours post-infusion	Rating of symptoms on HCL-32
Heart rate	4 hours post-infusion	Heart rate change from baseline
Respiratory rate	4 hours post-infusion	change in respiratory rate from baseline.

Trial Locations

Locations (1)

Clinical Research Facility, King's College Hospital; 🇬🇧 London, United Kingdom