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Schizophrenic PsychosesPhase 2NACPSYNCT01354132

N-Acetyl-Cysteine (NAC) in Early Phase Schizophrenia Spectrum Psychosis

A Phase 2 study testing n-acetylcysteine in people with Schizophrenic Psychoses, run by Beth Israel Deaconess Medical Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The investigators seek to examine the effect of add-on N-Acetyl-Cysteine (NAC) in the early phase of schizophrenia spectrum illness in collaboration with researchers Kim Do, PhD, and Philippe Conus, MD in Switzerland. Read more about this study

Who is it for?
Ages 18 to 35 years
Conditions the study is for
Schizophrenic Psychoses
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
2 sitesUnited States
Study dates
May 2011to Aug 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 35 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Capacity to provide informed consent
  • DSM IV TR diagnosis of schizophrenia, schizophreniform, schizoaffective
  • Psychiatric and medical stability
  • Prescribing clinician's premission to participate, assurance of medical stability
  • Having met threshold criteria for psychosis on CAARMS (Comprehensive Assessment of at Risk Mental States Scale) Psychosis subscale
  • Up to 12 months of antipsychotic treatment

Who cannot join

  • Severe medical comorbidities
  • Previous cerebral trauma
  • Substance induced psychosis or organic psychosis
  • Mental retardation
  • NAC allergy
  • Pregnancy, females and males planning pregnancy
  • Treatment with antioxidants
  • Insufficient command of English

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Massachusetts Mental Health Center

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Effects of Oral N-Acetyl-Cysteine (NAC) in the Early Phase of Schizophrenia Spectrum Psychosis: Randomized, Parallel, Double- Blind, Placebo Controlled Trial

The investigators seek to examine the effect of add-on N-Acetyl-Cysteine (NAC) in the early phase of schizophrenia spectrum illness in collaboration with researchers Kim Do, PhD, and Philippe Conus, MD in Switzerland. Modifications of brain structure are thought to occur during the pre-illness phase and around the transition to psychosis. Therefore, studying new treatments that could target changes occurring during this period is of critical importance.

Aims:

Does add-on NAC treatment in early psychosis influence:

  • positive and negative symptoms
  • extrapyramidal side-effects of other medication
  • plasma concentration of glutathione
  • Mismatch Negativity, a physiological marker
Read the detailed description

The study proposes that a glutathione deficit leading to an abnormal response to oxidative stress is a vulnerability factor, combined with other brain specific factors, in brain functioning of some individuals with schizophrenia (Do et al., 2010). N-acetyl-cysteine is hypothesized to cross the blood-brain barrier and increase glutathione in the brain.

Being tested
n-acetylcysteine, Placebo
Keywords
schizophrenia, schizoaffective, schizophreniform, early schizophrenia spectrum psychosis
Medical subject headings
Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • n-acetylcysteineDrug

    Also called PharmaNAC

    900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

  • PlaceboDrug

    Placebo tablets are placed in water or juice in the AM and PM

Study groups in NCT01354132
Study groupRoleWhat they receive
n-acetyl-cysteineActive comparatorN-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks
Receives: Drug: n-acetylcysteine
PlaceboPlacebo comparatormatching effervescent tablets in water 2 in am and 1 in pm
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Negative Symptoms of Schizophrenia as Measured on the PANSS

    Positive and Negative Symptom Scale was used to assess psychopathology. The sum of items N1 - N7 including N1) blunted affect, N2) emotional withdrawal, N3) poor rapport, N4) passive apathetic social withdrawal, N5) difficulty in abstract thinking, N6) lack of spontaneity and flow of conversation, and N7) sterotyped thinking were used to analyze negative symptoms of schizophrenia and were assessed for the previous week:

    RATING SCALE

    1: Absent 2: Minimal 3: Mild 4: Moderate 5: Moderate Severe 6: Severe 7: Extreme The higher the score the worse the symptoms. The lowest possible score is 7 and the highest possible score is 49 .

    Measured: at 6 months

Secondary outcomes (20)
  1. Change in Positive Symptoms (PANSS)

    Positive and Negative Symptom Scale was used to assess psychopathology. The Positive symptom subscale of schizophrenia includes the sum of items P1 -P7 including P1) Delusions, P2) conceptual Disorganization, P3) Hallunicatory Behavior, P4) Excitement, P5) Grandiosity, P6) Suspiciousness and Persecution, and P7) Hostility and were assessed for the previous week:

    RATING SCALE

    1: Absent 2: Minimal 3: Mild 4: Moderate 5: Moderate Severe 6: Severe 7: Extreme The higher the score the worse the symptoms. The lowest possible score is 7 and the highest possible score is 49 .

    Measured: at 6 months

  2. Global Assessment of Functioning (GAF)

    Measure Description: Clinical Measure of Global level of Symptoms (Sx) and Functioning from 1 (Worst) to 100 (Best) in groups of 10:

    100 - 91: Superior functioning 90 - 81: Absent or minimal Sx 80 - 71: If symptoms are present and expected 70 - 61:Some mild Sx 60 - 51: Moderate Sx 50 - 41: Serious Sx 40 - 31: Some impairment in reality testing or communication 30 - 21: Behavior is considerably influenced by delusions or hallucinations 20 - 11: Some danger of hurting self or others 10 - 1: Persistent danger of severely hurting self or others

    Measured: at 6 months

  3. Social and Occupational Functioning Assessment Scale (SOFAS)

    Measure of social and occupational functioning using the Social and Occupational Functioning Assessment Scale Measure Description: Rating of Overall Social and Occupational Functioning on a scale of 1 (worst) to 100 (best) in groups of 10:

    100-91: Superior functioning 90-81: Good functioning 80-71: Slight impairment 70-61: Some difficulty 60-51: Moderate difficulty 50-41: Serious impairment 40-31: Major impairment 30-21: Inability to function in almost all areas 20-11: Unable to function independently 10-1: Unable to function without harming self or others

    Measured: at 6 months

  4. Change in Cognition and Working Memory (MATRICS) Speed of Processing

    The MATRICS is neurocognitive battery designed to assess cognition. Processing speed is a composite score including the following tests: Trail Making Test, BACS: Symbol Coding, Category Fluency: Animal Naming. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

    Measured: at 6 months

  5. Change in Cognition and Working Memory (MATRICS) Working Memory

    The MATRICS is neurocognitive battery designed to assess cognition. Working Memory score is a composite score based on the following sub-test WMS-III Spatial Span and Letter-Number Span. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

    Measured: at 6 months

  6. Change in Cognition and Working Memory (MATRICS) Attention and Vigilance

    The MATRICS is neurocognitive battery designed to assess cognition. Sustained attention and Vigilance is a composite score based on the Continuous Performance Test -Identical Pairs. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

    Measured: at 6 months

  7. Change in Cognition and Working Memory (MATRICS) Verbal Learning

    The MATRICS is neurocognitive battery designed to assess cognition. Verbal Learning is a composite score based on the Hopkins Verbal Learning Test-Revised: Immediate Recall. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

    Measured: at 6 months

  8. Change in Cognition and Working Memory (MATRICS) Visual Learning

    The MATRICS is neurocognitive battery designed to assess cognition. Visual Learning is a composite score based on the Brief Visuospatial Memory test - Revised: Immediate Recall. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

    Measured: at 6 months

  9. Change in Cognition and Working Memory (MATRICS) Reasoning and Problem Solving

    The MATRICS is neurocognitive battery designed to assess cognition. Problem Solving is a composite score based on the NAB Mazes. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

    Measured: at 6 months

  10. Change in Blood Level of Glutathione

    Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids. The level of glutathione is measured in blood cells.

    Measured: at 6 months

  11. Blood Plasma Level of Cysteine

    Cysteine is an amino acid, a building block for proteins and is used throughout the body and was measured in blood plasma.

    Measured: at 6 months

  12. GPxbc Glutathione Peroxidase Activity in Blood Cells

    GPxBC is a measurement of glutathiione peroxidase enzymatic activity in glutathione synthesis and the redox system in blood cells. Measured as umol/min/gHb from blood cells.

    Measured: at 6 months

  13. Glutamine Brain Level for NAC Group

    Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.

    Measured: at 6 months

  14. Glutamine Brain Level for Placebo Group

    Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.

    Measured: at 6 months

  15. Glutamate Brain Level for NAC Group

    Brain marker, glutamate, was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutamate is an excitatory neurotransmitter in the brain.

    Measured: at 6 months

  16. Glutamate Brain Level for Placebo Group

    Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.

    Measured: at 6 months

  17. Glutathione Brain Level for NAC Group

    measured by H-MRS in the medial prefrontal cortex Brain markers, glutathione was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids.

    Measured: at 6 months

  18. Glutathione Brain Level for Placebo Group

    measured by H-MRS in the medial prefrontal cortex Brain markers, glutathione was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids.

    Measured: at 6 months

  19. Myo-Inositol Brain Level for the NAC Group

    Myo-Inositol is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS)MRS and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.

    Measured: at 6 months

  20. Myo-Inositol Brain Level for Placebo Group

    Myo-Inositol is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS)MRS and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.

    Measured: at 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2011 (estimated)
  2. Study startMay 2011
  3. Primary completionAug 2014
  4. Study completionAug 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01354132
Sponsor's protocol ID
2008P000460
Other IDs
107865
Acronym
NACPSY
Status last verified
Jun 2017
First submitted
13 May 2011
Last updated
5 Jul 2017
Data monitoring committee
Yes

Publications

  • Do KQ, Conus P, Cuenod M. Redox dysregulation and oxidative stress in schizophrenia: nutrigenetics as a challenge in psychiatric disease prevention. World Rev Nutr Diet. 2010;101:131-153. doi: 10.1159/000314518. Epub 2010 Apr 30. No abstract available.

    PubMed 20436260

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing n-acetylcysteine in people with Schizophrenic Psychoses, run by Beth Israel Deaconess Medical Center at 2 sites in United States.

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 6 inclusion and 8 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 5 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change in Negative Symptoms of Schizophrenia as Measured on the PANSS (time frame: at 6 months). 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 NCT01354132, which also lists 1 linked publication.

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 5 Jul 2017.

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