Effect of N-acetylcysteine on brain glutamate

• Research type

  Research Study

• Full 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

• IRAS ID

  152963

• Contact name

  Alice Egerton

• Contact email

  alice.egerton@kcl.ac.uk

• Sponsor organisation

  King's College London

• Duration of Study in the UK

  3 years, 0 months, 1 days

• Research summary

  Approximately 2/3 of patients show a suboptimal response to antipsychotic treatment. There are very limited treatment options when standard antipsychotics fail. 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 be therapeutic. This study tests whether it is possible to reduce brain glutamate levels in psychotic disorders.

  N-acetyl cysteine (NAC) is a nutritional supplement and medicine. The only published clinical trial of NAC in schizophrenia indicated a reduction in symptoms (Berk et al., 2008). The effects of NAC on brain glutamate in schizophrenia are unknown. However NAC can reduce brain glutamate in cocaine addiction (Schmaal et al., 2012).

  This is a small pilot study to determine whether a single administration of NAC can reduce brain glutamate levels in schizophrenia. 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 schizophrenia or other 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.

  If the results from this study are encouraging, we hope to proceed to a larger study of the effects of longer-term NAC administration on symptoms, glutamate and brain activity in schizophrenia.

  References:
  1. Egerton et al., NPP 2012 37:2515
  2. Demjaha, Egerton et al., Biol Psych, 2013, 25
  3. Berk et al., Biol Psych 2008 64,36
  4. Schmaal et al., NPP 2012 37:2143

• REC name

  London - Harrow Research Ethics Committee

• REC reference

  14/LO/2213

• Date of REC Opinion

  4 Feb 2015

• REC opinion

  Further Information Favourable Opinion