Clinical trial NCT02176044: The Effect of Nitric Oxide on Spatial Working Memory in Patients With Schizophrenia - Pilot Study
Official title: The Effect of Nitric Oxide on Spatial Working Memory in Patients With Schizophrenia - Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Keywords: Nitric Oxide
Sodium Nitroprusside
Spatial Working Memory
Psychosis
Schizophrenia
Lead sponsor: King's College London
Sponsor class: OTHER
First posted: 2014-06-26
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Spatial Working Memory
timeFrame: 4 hours post-infusion
Secondary outcomes:
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: 4 hours post-infusion
measure: Brief Psychiatric Rating Scale (BPRS)
timeFrame: 4 hours post-infusion
measure: Quick Inventory of Depressive Symptomatology (QIDS)
timeFrame: 4 hours post-infusion
measure: Hypomania Checklist (HCL-32)
timeFrame: 4 hours post-infusion
measure: Blood pressure
timeFrame: 4 hours post-infusion
measure: Heart rate
timeFrame: 4 hours post-infusion
measure: Respiratory rate
timeFrame: 4 hours post-infusion
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Clinical Research Facility, King's College Hospital
Study officials:
affiliation: King's College London
name: James Stone, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stone JM, Morrison PD, Koychev I, Gao F, Reilly TJ, Kolanko M, Mohammadinasab A, Kapur S, McGuire PK. The effect of sodium nitroprusside on psychotic symptoms and spatial working memory in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial. Psychol Med. 2016 Dec;46(16):3443-3450. doi: 10.1017/S0033291716002245. Epub 2016 Sep 22.