NOC: The Role of Nitric Oxide in Cognition in Schizophrenia

Sponsor

King's College London (Other)

Overall Status

Completed

CT.gov ID

NCT02906553

Collaborator

South London and Maudsley NHS Foundation Trust (Other)

Enrollment

Location

Arms

30.9

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Psychotic Disorders	Drug: Glyceryl Trinitrate Drug: Placebo	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Sep 1, 2016

Actual Primary Completion Date :

Apr 1, 2019

Actual Study Completion Date :

Apr 1, 2019

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Glyceryl Trinitrate

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

Drug: Glyceryl Trinitrate

Placebo Comparator: Placebo

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

Drug: Placebo

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts 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