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

King's College London

Status and phase: Completed; Phase 1

Conditions: Schizophrenia

Treatments: Other: Placebo; Drug: Sodium Nitroprusside infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT02176044

NOSMEM01

Details and patient eligibility

About

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.

Enrollment: 21 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

21 participants in 2 patient groups, including a placebo group

Glucose infusion

Placebo Comparator group

Description:

Placebo infusion of sterile 5% glucose - 500ml infused over 4 hours.

Treatment:

Other: Placebo

Sodium Nitroprusside infusion

Active Comparator group

Description:

Sodium nitroprusside dissolved in 5% glucose solution. Infused at 0.5mcg/kg/min for 4 hours.

Treatment:

Drug: Sodium Nitroprusside infusion