The Role of Nitric Oxide in Cognition in Schizophrenia

Not Applicable

Completed

• Conditions: Psychotic Disorders; Schizophrenia
• Interventions: Drug: Placebo; Drug: Glyceryl Trinitrate

• Registration Number: NCT02906553
• Lead Sponsor: King's College London

Brief Summary

This study evaluates the role of the Nitric Oxide system in cognition in patients with schizophrenia. Participants will be randomised to 2 equal groups and receive either the Nitric Oxide donor molecule glyceryl trinitrate, or a placebo. Performance on several cognitive tasks will be assessed.

Detailed Description

Nitric oxide \[NO\] is a gaseous neurotransmitter substance found in the brain. Nitric oxide is integrated with the glutamate system. Glutamate has received considerable attention as an important factor in the cognitive distortions and cognitive impairments that underlie schizophrenia. Deficits in glutamate in schizophrenia may impact upon cognition via the NO system, as glutamate receptors signal by way of NO.

Here the investigators aim to extend knowledge of glutamate-NO systems by directly examining the role of NO in cognition in patients with psychosis. We aim to assess the role of the NO system in cognition, downstream of glutamate and before patients are started on any anti-psychotic medication which perturb brain neurochemistry.

The primary outcome measure is change in a particular style of cognition referred to as 'jumping to conclusions' following the administration of a potent Nitric Oxide donor molecule \[glyceryl trinitrate (GTN)\], under placebo-controlled, double-blind conditions. This will shed light on the direct role of NO in cognition in psychosis, beyond the glutamate system.

Study Timeline

• Study Start: 2016-09
• Study First Submitted: 2016-09-15
• Study First Submitted QC: 2016-09-15
• Study First Posted: 2016-09-20
• Status Verified: 2018-03
• Primary Completion: 2019-04
• Study Completion: 2019-04
• Last Update Submitted: 2019-08-12
• Last Update Posted: 2019-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

• 18-40 years of age
• Patients undergoing an acute psychotic episode (defined as score > 4 on question P1 of the PANSS positive subscale) requiring full-time hospitalisation according to clinical referral by the relevant mental health service
• Demonstrates capacity and willing to give informed consent
• Female participants willing to have a pregnancy test before treatment
• Currently unmedicated with antipsychotic medication

Exclusion Criteria

• Major physical illness
• Prior history of intolerance to glyceryl trinitrate
• Homicidal or suicidal
• Pregnant or breast feeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	The formulation composition of the placebo will be the same as the active spray minus the Glyceryl Trinitrate.
Glyceryl Trinitrate	Glyceryl Trinitrate	Glyceryl Trinitrate, sublingual spray, 3 x 0.4mg dose, once per day for 3 days in total.

Primary Outcome Measures

Name	Time	Method
The emotionally salient version of the Jumping to Conclusions (JTC) task	Change in performance from baseline to Day1, Day 2, Day 3, Day 7

Secondary Outcome Measures

Name	Time	Method
The Hopkins Verbal Learning Task - Revised, immediate recall	Change from baseline to Day1, Day 2, Day 3, Day 7
Positive and negative syndrome scale (PANSS) (videotaped)	Change from baseline to Day1, Day 2, Day 3, Day 7
The Bond-Lader Visual Analog Scales	Change from baseline to Day1, Day 2, Day 3, Day 7

Trial Locations

Locations (1)

South London and Maudsley; 🇬🇧 London, United Kingdom