The Role of Nitric Oxide in Cognition in Schizophrenia

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Role of Nitric Oxide in Cognition in Schizophrenia; The NOC Study (Nitric Oxide in Cognition)

Conditions
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Schizophrenia, Psychotic Disorders

Intervention / Treatment
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* Drug: Glyceryl Trinitrate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glyceryl Trinitrate<br>Glyceryl Trinitrate, sublingual spray, 3 x 0.4mg dose, once per day for 3 days in total. | Drug: Glyceryl Trinitrate<br> <br> |
| Placebo Comparator: Placebo<br>The formulation composition of the placebo will be the same as the active spray minus the Glyceryl Trinitrate. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nitric Oxide, Cognition