Effect of N-acetylcysteine on Brain Glutamate

Psychosis Clinical Trial

— NAC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02483130
• Other study ID #: BRCNAC
• Status: Completed
• Phase: N/A
• First received: June 24, 2015
• Last updated: March 7, 2018
• Start date: June 2015
• Est. completion date: February 28, 2017

Study information

• Verified date: August 2016
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 28, 2017
• Est. primary completion date: February 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Psychosis

Intervention

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.

Locations

Country	Name	City	State
United Kingdom	Institute of Psychiatry, Psychology and Neuroscience	Denmark Hill	London

Sponsors (1)

Lead Sponsor	Collaborator
King's College London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Brain perfusion	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.	One hour post capsule
Secondary	Regional activity and connectivity	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.	One hour post capsule