N-acetylcysteine (NAC) for Improving Cognitive Dysfunction in Schizophrenia

NCT01885338 | Completed Phase 1

• 1 other identifier: PCC 2013-020208
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the effect of the dietary supplement N-acetylcysteine (NAC) on electrophysiologic (EEG) markers related to cognition, as well as performance on psychological tests measuring cognition. The primary hypothesis is that participants treated with NAC will show improvements in cognitive function, as measured by EEG and performance-based tests.

Conditions

Schizophrenia

Keywords

Schizophrenia; Cognition; Neurocognition; N-Acetylcysteine; NAC; EEG

Outcome Measures

Primary Outcomes (3)

• EEG: Change in Mismatch Negativity Amplitude

  A passive attention auditory oddball paradigm will be used to assess MMN.

  Change from baseline to 8 weeks

• EEG: Change in P300 Amplitude

  P300 will be measured using an active attention auditory oddball paradigm.

  Change from baseline to 8 weeks

• EEG: Change in Gamma Synchrony Evoked Power and Phase Synchronization

  Stimuli will consist of 1-msec 93-dB clicks presented in 500-msec trains presented at 40 Hz, in 3 separate blocks with 200 trials per block. Continuous data will be epoched at -100 to 700 ms relative to stimulus onset and baseline corrected to the average of the prestimulus interval. For evoked gamma power analyses, averages will be computed on a minimum of 120 artifact-free epochs in each block. The averaged epochs across the click trains (0-512 msec) will be transformed into power spectra by fast Fourier transform (FFT). The 40-Hz power spectra will be averaged across 36-45 Hz. Time/frequency intertrial coherence analyses will be performed to assess intertrial coherence of the stimulus-driven EEG signals. In this analysis, coherence ranges from 0 (non-phase-locked random activity) to 1 (activity that is fully locked in phase across individual trials). Responses at electrode Fz will be analyzed.

  Change from baseline to 8 weeks

Secondary Outcomes (4)

• EEG: Change in Visual Cortical Plasticity

  Change from baseline to 8 weeks

• Change in MATRICS Consensus Cognitive Battery composite score

  Change from baseline to 8 weeks

• Change in Positive and Negative Syndrome Scale (PANSS) total score

  Change from baseline to 8 weeks

• Change in Clinical Assessment Interview for Negative Symptoms (CAINS) scores

  Change from baseline to 8 weeks

Other Outcomes (5)

• MIRECC Global Assessment of Functioning (MIRECC GAF)

  4 weeks, 8 weeks

• Clinical Global Impression (CGI-S and CGI-I

  4 weeks, 8 weeks

• Udvalg for Kliniske Undersøgelser (UKU) Side Effects Rating Scale:

  2 weeks, 4 weeks, 8 weeks

Study Arms (2)

N-acetylcysteine (NAC)

EXPERIMENTAL

Capsules containing N-acetylcysteine 600mg, with inactive ingredients of cellulose, L-leucine, and silica used as filler. Dosage is 2 capsules by mouth twice daily for 8 weeks.

Drug: N-acetylcysteine (NAC)

Inactive placebo capsule

PLACEBO COMPARATOR

A placebo capsule is used that is identical to the active treatment but lacks NAC. The inactive ingredients in the placebo capsule are cellulose, L-leucine, and silica. Dose is 2 capsules by mouth twice daily for 8 weeks.

Drug: Inactive placebo capsule

Interventions

N-acetylcysteine (NAC) DRUG

Also known as: N-acetyl-L-cysteine, NAC

N-acetylcysteine (NAC)

Inactive placebo capsule DRUG

Also known as: Placebo capsule, Sugar pill

Inactive placebo capsule

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets DSM-IV-TR criteria for schizophrenia.
• At least 3 months since any psychiatric hospitalization
• At least 1 month since meeting criteria for having a major depressive episode
• At least 6 months since any behaviors suggesting any potential danger to self or others
• Currently prescribed an antipsychotic medication, with dose not varying \>50% over 3 months prior to study participation
• No acute medical problems that could interfere with study participation
• Chronic medical problems consistently treated and stable for at least 3 months prior to participation
• Ability to provide informed consent and cooperate with study procedures

You may not qualify if:

• Documented history of IQ less than 70 or severe learning disability
• History of treatment with electroconvulsive therapy within 6 months prior to study participation
• History of neurological or neuropsychiatric condition (e.g., stroke, severe traumatic brain injury, epilepsy, etc.) that could confound assessments
• Documented history of persistent substance abuse or dependence within 3 months prior to study participation

Sponsors & Collaborators

• VA Greater Los Angeles Healthcare System: lead
• VISN 22 Mental Illness Research, Education, and Clinical Center: collaborator
• American Psychiatric Foundation: collaborator

Study Sites (1)

VA West Los Angeles Healthcare Center

Los Angeles, California, 90073, United States

Location

Related Publications (7)

• Berk M, Malhi GS, Gray LJ, Dean OM. The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci. 2013 Mar;34(3):167-77. doi: 10.1016/j.tips.2013.01.001. Epub 2013 Jan 29.

  PMID: 23369637 BACKGROUND

• Cabungcal JH, Steullet P, Kraftsik R, Cuenod M, Do KQ. Early-life insults impair parvalbumin interneurons via oxidative stress: reversal by N-acetylcysteine. Biol Psychiatry. 2013 Mar 15;73(6):574-82. doi: 10.1016/j.biopsych.2012.09.020. Epub 2012 Nov 7.

  PMID: 23140664 BACKGROUND

• Shungu DC. N-acetylcysteine for the treatment of glutathione deficiency and oxidative stress in schizophrenia. Biol Psychiatry. 2012 Jun 1;71(11):937-8. doi: 10.1016/j.biopsych.2012.03.025. No abstract available.

  PMID: 22579304 BACKGROUND

• Carmeli C, Knyazeva MG, Cuenod M, Do KQ. Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial. PLoS One. 2012;7(2):e29341. doi: 10.1371/journal.pone.0029341. Epub 2012 Feb 22.

  PMID: 22383949 BACKGROUND

• das Neves Duarte JM, Kulak A, Gholam-Razaee MM, Cuenod M, Gruetter R, Do KQ. N-acetylcysteine normalizes neurochemical changes in the glutathione-deficient schizophrenia mouse model during development. Biol Psychiatry. 2012 Jun 1;71(11):1006-14. doi: 10.1016/j.biopsych.2011.07.035. Epub 2011 Sep 25.

  PMID: 21945305 BACKGROUND

• Dean O, Giorlando F, Berk M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci. 2011 Mar;36(2):78-86. doi: 10.1503/jpn.100057.

  PMID: 21118657 BACKGROUND

• 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.

  PMID: 18436195 BACKGROUND

MeSH Terms

Conditions

Schizophrenia

Interventions

Acetylcysteine; Sugars

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Stephen R Marder, M.D.

  VA Greater Los Angeles

  PRINCIPAL INVESTIGATOR

• Michael C Davis, M.D., Ph.D.

  VA Greater Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fellow / Physician

Study Record Dates

• First Submitted: June 17, 2013
• First Posted: June 24, 2013
• Study Start: June 1, 2013
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: June 4, 2015

Record last verified: 2015-06

Locations

US (1)