Effect of N-acetylcysteine on Brain Glutamate

NCT02483130 | Completed

• 1 other identifier: BRCNAC
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Psychosis

Outcome Measures

Primary Outcomes (1)

• Reduction in brain glutamate

  The within-subjects difference in brain glutamate concentration following a single oral administration of placebo compared to 2400mg N-acetylcysteine

  One hour post capsule

Secondary Outcomes (2)

• Brain perfusion

  One hour post capsule

• Regional activity and connectivity

  One hour post capsule

Study Arms (1)

NAC or Placebo

Participants will receive 2400mg capsules of N-Acetylcysteine or placebo

Dietary Supplement: N-Acetylcysteine; Other: Placebo

Interventions

N-Acetylcysteine DIETARY_SUPPLEMENT

Participants will receive 2400mg of N-Acetylcysteine orally via 6 x 400mg capsules.

NAC or Placebo

Placebo OTHER

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

NAC or Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• King's College London: lead

Study Sites (1)

Institute of Psychiatry, Psychology and Neuroscience

Denmark Hill, London, SE5 8AF, United Kingdom

Location

Related Publications (3)

• Egerton A, Brugger S, Raffin M, Barker GJ, Lythgoe DJ, McGuire PK, Stone JM. Anterior cingulate glutamate levels related to clinical status following treatment in first-episode schizophrenia. Neuropsychopharmacology. 2012 Oct;37(11):2515-21. doi: 10.1038/npp.2012.113. Epub 2012 Jul 4.

  PMID: 22763619 BACKGROUND

• Demjaha A, Egerton A, Murray RM, Kapur S, Howes OD, Stone JM, McGuire PK. Antipsychotic treatment resistance in schizophrenia associated with elevated glutamate levels but normal dopamine function. Biol Psychiatry. 2014 Mar 1;75(5):e11-3. doi: 10.1016/j.biopsych.2013.06.011. Epub 2013 Jul 25. No abstract available.

  PMID: 23890739 BACKGROUND

• Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Judd F, Katz F, Katz P, Ording-Jespersen S, Little J, Conus P, Cuenod M, Do KQ, Bush AI. N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008 Sep 1;64(5):361-8. doi: 10.1016/j.biopsych.2008.03.004. Epub 2008 Apr 23.

  PMID: 18436195 BACKGROUND

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.

MeSH Terms

Conditions

Psychotic Disorders

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• James H McCabe

  King's College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2015
• First Posted: June 26, 2015
• Study Start: June 1, 2015
• Primary Completion: February 28, 2017
• Study Completion: February 28, 2017
• Last Updated: March 8, 2018

Record last verified: 2016-08

Locations

GB (1)