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Effect of N-acetylcysteine on Brain Glutamate (NAC)

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ClinicalTrials.gov Identifier: NCT02483130
Recruitment Status : Completed
First Posted : June 26, 2015
Last Update Posted : March 8, 2018
Sponsor:
Information provided by (Responsible Party):
King's College London

Brief Summary:
A double-blind, placebo controlled, crossover study to determine whether a single dose of N-acetylcysteine (a nutritional supplement) can reduce brain glutamate levels in patients with a psychotic disorder. Secondary outcomes are to determine the pattern of alteration in brain perfusion and activity following a single dose of N-acetylcysteine.

Condition or disease Intervention/treatment
Psychosis Dietary Supplement: N-Acetylcysteine Other: Placebo

Detailed Description:

This is a physiological, proof-of-concept study designed to investigate whether a single administration of N-acetylcysteine can reduce brain glutamate levels in people with psychotic disorders.

Previous research suggests that poor response to antipsychotics may be linked to increased levels of glutamate in the brain (Egerton et al., 2012; Demjaha, Egerton et al., 2013). Reducing brain glutamate levels may therefore be therapeutic. This study tests whether it is possible to reduce brain glutamate levels in psychotic disorders.

This is a small pilot study to determine whether a single administration of NAC can reduce brain glutamate levels in psychosis. At the same time, we will also examine the effects of NAC on brain resting perfusion and activity, to gain more information about how NAC may be acting.

This study will recruit participants with a previous diagnosis of a psychotic disorder. There will be three study visits, 1-2 weeks apart. The first visit will involve a physical health check, blood sample and an interview to assess current symptoms and confirm medical history. On the second and third visits participants will have an MRI scan, lasting one hour, after taking capsules containing either 2400mg NAC or placebo.


Study Type : Observational
Actual Enrollment : 20 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: A Randomised Controlled Double Blind Crossover Study of the Effect of a Single Dose of N-acetylcysteine Versus Placebo on Brain Glutamate in Patients With Psychotic Disorders
Study Start Date : June 2015
Actual Primary Completion Date : February 28, 2017
Actual Study Completion Date : February 28, 2017

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
NAC or Placebo
Participants will receive 2400mg capsules of N-Acetylcysteine or placebo
Dietary Supplement: N-Acetylcysteine
Participants will receive 2400mg of N-Acetylcysteine orally via 6 x 400mg capsules.

Other: Placebo
Participants will receive 2400mg of placebo orally via 6 x 400mg capsules.




Primary Outcome Measures :
  1. Reduction in brain glutamate [ Time Frame: One hour post capsule ]
    The within-subjects difference in brain glutamate concentration following a single oral administration of placebo compared to 2400mg N-acetylcysteine


Secondary Outcome Measures :
  1. Brain perfusion [ Time Frame: One hour post capsule ]
    The within-subjects change in regional brain perfusion, as assessed using pulsed continuous arterial spin labelling (pCASL) MRI, following a single oral administration of placebo compared to 2400mg N-acetylcysteine.

  2. Regional activity and connectivity [ Time Frame: One hour post capsule ]
    The within-subjects change in regional brain activity or connectivity, as assessed using resting state functional magnetic resonance imaging (rsfMRI), following a single oral administration of placebo compared to 2400mg N-acetylcysteine.


Biospecimen Retention:   Samples With DNA

Samples are collected for two purposes.

  1. Participants are invited to donate samples to the BRC Bioresource. These samples may be used in the future for genetic, epigenetic, metabolomic or proteomic analysis.
  2. Participants will also be asked for a blood sample after completion of each MRI scan. These will be used to measure blood glutathione levels, which may be altered by N-acetylcysteine and therefore provide indication of pharmacological effect.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients will be identified:

  1. Via South London and Maudsley (SLaM) clinical teams.
  2. If they have previously indicated to local research teams that they would like to be contacted about future research.

2. Through the SLaM NIHR Bioresource, including patients in CRIS, the research informatics database, who have given consent to be contacted about research projects.

Criteria

Inclusion Criteria:

  • Over 18 years of age
  • Diagnosis of a psychotic disorder
  • Have mental capacity to consent

Exclusion Criteria:

  • Diagnosed drug or alcohol dependency, with the exception of nicotine
  • Pregnancy, as determined through a urine pregnancy test
  • Presence of any physical health abnormality which may impact on safety to participate in the research, as determined by a study clinician on the basis of the physical health check and the available medical information.
  • Presence of electronic or metallic implants contraindicated to MRI scanning at 3 Tesla, or presence of any other contraindication to MRI
  • History of asthma
  • History of epilepsy or any other seizure
  • Under 18 years of age
  • Lacking mental capacity to consent
  • Current or previous use of NAC
  • Currently prescribed clozapine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02483130


Locations
United Kingdom
Institute of Psychiatry, Psychology and Neuroscience
Denmark Hill, London, United Kingdom, SE5 8AF
Sponsors and Collaborators
King's College London
Investigators
Principal Investigator: James H McCabe King's College London

Publications:
Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT02483130     History of Changes
Other Study ID Numbers: BRCNAC
First Posted: June 26, 2015    Key Record Dates
Last Update Posted: March 8, 2018
Last Verified: August 2016

Additional relevant MeSH terms:
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes