PsychosisNACNCT02483130
Effect of N-acetylcysteine on Brain Glutamate
An observational study of Psychosis, run by King's College London at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Psychosis
- What is being tested?
- N-Acetylcysteine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2015to 28 Feb 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Over 18 years of age
- Diagnosis of a psychotic disorder
- Have mental capacity to consent
Who cannot join
- 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
Show all 10Show fewer
- Under 18 years of age
- Lacking mental capacity to consent
- Current or previous use of NAC
- Currently prescribed clozapine
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Institute of Psychiatry, Psychology and Neuroscience
Denmark Hill, London, SE5 8AF
About this study
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
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.
Read the 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.
- Conditions
- Psychosis
- Being tested
- N-Acetylcysteine, Placebo
- Medical subject headings
- Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-AcetylcysteineDietary supplement
Participants will receive 2400mg of N-Acetylcysteine orally via 6 x 400mg capsules.
PlaceboOther
Participants will receive 2400mg of placebo orally via 6 x 400mg capsules.
| Study group | Role | What they receive |
|---|---|---|
| NAC or Placebo | Participants will receive 2400mg capsules of N-Acetylcysteine or placebo Receives: Dietary Supplement: N-Acetylcysteine; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in brain glutamate
The within-subjects difference in brain glutamate concentration following a single oral administration of placebo compared to 2400mg N-acetylcysteine
Measured: One hour post capsule
Secondary outcomes (2)
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.
Measured: One hour post capsule
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.
Measured: One hour post capsule
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2015 (estimated)
- Study startJun 2015
- Primary completion28 Feb 2017
- Study completion28 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PsychosisStudies of the same condition, open and under way.
- More trials run by King's College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James H McCabe, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02483130
- Sponsor's protocol ID
- BRCNAC
- Acronym
- NAC
- Status last verified
- Aug 2016
- First submitted
- 24 Jun 2015
- Last updated
- 8 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22763619Demjaha 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.
PubMed 23890739Berk 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.
PubMed 18436195
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02483130
- Acronym / sponsor ID
- NAC / BRCNAC
- Conditions
- Psychosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- 28 Feb 2017 (actual)
- Study completion
- 28 Feb 2017 (actual)
- First posted
- 26 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NAC or Placebo | – | Dietary Supplement: N-Acetylcysteine, Other: PlaceboParticipants will receive 2400mg capsules of N-Acetylcysteine or placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- Over 18 years of age
- Diagnosis of a psychotic disorder
- Have mental capacity to consent
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-AcetylcysteineParticipants will receive 2400mg of N-Acetylcysteine orally via 6 x 400mg capsules. | Dietary supplement | NAC or Placebo |
| PlaceboParticipants will receive 2400mg of placebo orally via 6 x 400mg capsules. | Other | NAC or Placebo |
Primary outcome
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
2 secondary outcomes
Brain perfusion
Time frame: One hour post capsule
Regional activity and connectivity
Time frame: One hour post capsule
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2018.
- Background: PubMed 22763619Egerton 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.
- Background: PubMed 23890739Demjaha 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.
- Background: PubMed 18436195Berk 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James H McCabe principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Psychosis, run by King's College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in brain glutamate (time frame: One hour post capsule). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02483130, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2018.