The Role of Nitric Oxide in Cognition in Schizophrenia (NOC)

King's College London

Status: Completed

Conditions: Psychotic Disorders; Schizophrenia

Treatments: Drug: Placebo; Drug: Glyceryl Trinitrate

Study type: Interventional

Funder types: Other

Identifiers

NCT02906553

16/LO/1102

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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19 participants in 2 patient groups, including a placebo group

Glyceryl Trinitrate

Experimental group

Description:

Glyceryl Trinitrate, sublingual spray, 3 x 0.4mg dose, once per day for 3 days in total.

Treatment:

Drug: Glyceryl Trinitrate

Placebo

Placebo Comparator group

Description:

The formulation composition of the placebo will be the same as the active spray minus the Glyceryl Trinitrate.

Treatment:

Drug: Placebo