NCT02176044

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at below P25 for phase_1 schizophrenia

Timeline
Completed

Started Aug 2014

Typical duration for phase_1 schizophrenia

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 25, 2014

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 26, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

August 1, 2014

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2016

Completed
Last Updated

March 9, 2016

Status Verified

March 1, 2016

Enrollment Period

1.5 years

First QC Date

June 25, 2014

Last Update Submit

March 8, 2016

Conditions

Schizophrenia

Keywords

Nitric OxideSodium NitroprussideSpatial Working MemoryPsychosisSchizophrenia

Outcome Measures

Primary Outcomes (1)

  • Spatial Working Memory

    performance on Cambridge Neuropsychological Test Automated Battery spatial working memory task

    4 hours post-infusion

Secondary Outcomes (7)

  • Positive and Negative Syndrome Scale (PANSS)

    4 hours post-infusion

  • Brief Psychiatric Rating Scale (BPRS)

    4 hours post-infusion

  • Quick Inventory of Depressive Symptomatology (QIDS)

    4 hours post-infusion

  • Hypomania Checklist (HCL-32)

    4 hours post-infusion

  • Blood pressure

    4 hours post-infusion

  • +2 more secondary outcomes

Study Arms (2)

Glucose infusion

PLACEBO COMPARATOR

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

Other: Placebo

Sodium Nitroprusside infusion

ACTIVE COMPARATOR

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

Drug: Sodium Nitroprusside infusion

Interventions

Sodium Nitroprusside infusionDRUG
Sodium Nitroprusside infusion
PlaceboOTHER
Glucose infusion

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Clinical Research Facility, King's College Hospital

London, SE5, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 27655012DERIVED

MeSH Terms

Conditions

SchizophreniaPsychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental Disorders

Study Officials

  • James Stone, MBBS PhD

    King's College London

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 25, 2014

First Posted

June 26, 2014

Study Start

August 1, 2014

Primary Completion

February 1, 2016

Study Completion

February 1, 2016

Last Updated

March 9, 2016

Record last verified: 2016-03

Locations

GB(1)