The Effect of N-Acetyl Cysteine on Cortical Erosion in Early Stage Schizophrenia

NCT01339858 | Completed Phase 4 Results DMC

• 1 other identifier: 1008-12
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective of this study is to determine if NAC, added to existing antipsychotic treatment, is superior to placebo for cortical erosion in patients with early stage psychosis. The primary hypothesis is that there will be significantly less cortical erosion as measured by cortical thickness, cortical volume and cortical white matter density (assessed by DTI) in patients treated for 12 months with NAC as compared to those treated with placebo. The secondary objectives of this study are to determine if 12 months of NAC add-on treatment is superior to placebo for fMRI determined working memory and semantic memory tasks, cortical MR spectroscopy measures (glutathione, N-acetylaspartate, and glutamine/glutamate levels), electrophysiologically determined attention measures (e.g., mismatch negativity, P300), symptoms, functional measures and cognitive functioning.

Conditions

Schizophrenia; Psychotic Disorder NOS; Schizoaffective Disorder; Schizophreniform

Outcome Measures

Primary Outcomes (2)

• Cortical Thickness

  We anticipate that 12 months treatment with NAC as an add-on treatment will show significantly less cortical erosion as measured by cortical thickness than treatment with placebo

  12 months

• Cortical Volume

  We anticipate that 12 months treatment with NAC as an add-on treatment will show a difference in cortical volume than treatment with placebo

  12 months

Secondary Outcomes (8)

• Working Memory

  Baseline and 12 months

• Number of Participants With Glutamine/Glutamate Level Changes

  12 months

• Attention Measures

  12 months

• Symptoms of a Psychotic Disorder

  12 months

• Cognitive Functioning

  Baseline and 12 months

Study Arms (2)

N-Acetyl Cysteine

EXPERIMENTAL

NAC and matched placebo will be supplied in unmarked capsules. Each NAC capsule will contain 600 mg of NAC. Dosing will begin at 600 mg/d and titrated up over 5 weeks until a maximum dose of 3600 mg/d is reached. This approximate dose was effective and well tolerated in a recent study of treatment refractory obsessive-compulsive disorder by Krystal and colleagues at Yale (16). In addition, a double-blind placebo controlled trial recently completed at IUSM Riley Hospital in children (age 4 to 12 years) with autism spectrum disorders used doses ranging from 900 mg/day to 4200 mg/day and reported no serious adverse events and found the agent well tolerated (15). Dose adjustments downward to 1920 mg/d will be permitted if tolerability issues are encountered at the maximum dose.

Drug: N-Acetyl Cysteine

Sugar Pill

PLACEBO COMPARATOR

matched placebo

Other: sugar pill

Interventions

N-Acetyl Cysteine DRUG

NAC and matched placebo will be supplied in unmarked capsules. Each NAC capsule will contain 480 mg of NAC. Dosing will begin at 480 mg/d and titrated up by 480 mg/d each week until a maximum dose of 2880 mg/d (BID) is reached. This approximate dose was effective and well tolerated in a recent study of treatment refractory obsessive-compulsive disorder by Krystal and colleagues at Yale (16). In addition, a double-blind placebo controlled trial recently completed at IUSM Riley Hospital in children (age 4 to 12 years) with autism spectrum disorders used doses ranging from 900 mg/day to 4200 mg/day and reported no serious adverse events and found the agent well tolerated (15). Dose adjustments downward to 1920 mg/d will be permitted if tolerability issues are encountered at the maximum dose

N-Acetyl Cysteine

sugar pill OTHER

matched placebo will be supplied in unmarked capsules. Dosing regimen will be the same as in the N-Acetyl Cysteine arm.

Sugar Pill

Eligibility Criteria

• Age: 16 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with a DSM-IV diagnosis of schizophrenia, schizophreniform, schizoaffective, psychosis disorder NOS
• Age range 16-35 years
• Male or female
• Within 2 years of the first onset of psychotic symptoms that resulted in work/school/social dysfunction and/or treatment (PI will review potential subjects who have been experiencing symptoms \>2 years but \<5 years and will allow to enter the trial on a case-by-case basis)
• Ability to provide informed consent and/or assent (all subjects)
• For subjects 16 and 17 years of age, parental/guardian consent

You may not qualify if:

• Unstable medical conditions
• Active seizure disorder
• Pregnant or lactating women
• Females unwilling to utilize birth control
• Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, or ventriculoperitoneal shunt (because of MR studies).
• Known IQ less than 70
• DSM-IV-TR diagnosis of substance dependence (with the exception of nicotine or caffeine dependence)
• Psychotic symptoms secondary to substance use
• Considered a high risk for suicidal acts - active suicidal ideation with intent to act as determined by clinical interview
• HEALTHY CONTROL SUBJECTS
• The comparison subjects will consist of 40 healthy normal volunteers recruited from the community who will be age and gender matched to subjects diagnosed with a psychotic disorder entering the NAC treatment study
• Age range of 18-30 (inclusive) and able to give voluntary informed consent (Note: Subjects diagnosed with a psychotic disorder under the age of 18 will be age matched to control subjects aged 18).
• Male or Female
• Current severe mental disorder (Schizophrenia, schizophreniform disorder, other psychotic disorders, bipolar disorder, major depressive disorder)
• Known/documented IQ \< 70

Sponsors & Collaborators

• Indiana University: lead
• Stanley Medical Research Institute: collaborator

Study Sites (2)

Prevention and Recovery Center for Early Psychosis (PARC)

Indianapolis, Indiana, 46202, United States

Location

Indiana University Psychotic Disorders Clinic

Indianapolis, Indiana, 46222, United States

Location

Related Publications (1)

• Breier A, Liffick E, Hummer TA, Vohs JL, Yang Z, Mehdiyoun NF, Visco AC, Metzler E, Zhang Y, Francis MM. Effects of 12-month, double-blind N-acetyl cysteine on symptoms, cognition and brain morphology in early phase schizophrenia spectrum disorders. Schizophr Res. 2018 Sep;199:395-402. doi: 10.1016/j.schres.2018.03.012. Epub 2018 Mar 24.

  PMID: 29588126 DERIVED

MeSH Terms

Conditions

Schizophrenia; Mental Disorders; Psychotic Disorders

Interventions

Acetylcysteine; Sugars

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Alan Breier
• Organization: Indiana University Psychotic Disorders Program

abreier@iupui.edu

317-880-8495

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Study Record Dates

• First Submitted: April 19, 2011
• First Posted: April 21, 2011
• Study Start: May 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 8, 2019
• Results First Posted: May 8, 2019

Record last verified: 2019-04

Locations

US (2)