A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder

Logan K. Wink, Ryan Adams, Zemin Wang, James E. Klaunig, Martin H. Plawecki, David J. Posey, Christopher J. McDougle, Craig A. Erickson

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: Social impairment is a defining feature of autism spectrum disorder (ASD) with no demonstrated effective pharmacologic treatments. The goal of this study was to evaluate efficacy, safety, and tolerability of oral N-acetylcysteine (NAC), an antioxidant whose function overlaps with proposed mechanisms of ASD pathophysiology, targeting core social impairment in youth with ASD. Methods: This study was a 12-week randomized, double-blind, placebo-controlled trial of oral NAC in youth with ASD. Study participants were medically healthy youth age 4 to 12 years with ASD, weighing ≥15 kg, and judged to be moderately ill based on the Clinical Global Impressions Severity scale. The participants were randomized via computer to active drug or placebo in a 1:1 ratio, with the target dose of NAC being 60 mg/kg/day in three divided doses. The primary outcome measure of efficacy was the Clinical Global Impressions Improvement (CGI-I) scale anchored to core social impairment. To investigate the impact of NAC on oxidative stress markers in peripheral blood, venous blood samples were collected at screen and week 12. Results: Thirty-one patients were enrolled (NAC = 16, placebo = 15). Three participants were lost to follow-up, and three left the trial due to adverse effects. The average daily dose of NAC at week 12 was 56.2 mg/kg (SD = 9.7) with dose ranging from 33.6 to 64.3 mg/kg. The frequency of adverse events was so low that comparisons between groups could not be conducted. At week 12, there was no statistically significant difference between the NAC and placebo groups on the CGI-I (p > 0.69) but the glutathione (GSH) level in blood was significantly higher in the NAC group (p <0.05). The oxidative glutathione disulfide (GSSG) level increased in the NAC group, however only at a trend level of significance (p = 0.09). There was no significant difference between the NAC and placebo groups in the GSH/GSSG ratio, DNA strand break and oxidative damage, and blood homocysteine levels at week 12 (ps > 0.16). Conclusions: The results of this trial indicate that NAC treatment was well tolerated, had the expected effect of boosting GSH production, but had no significant impact on social impairment in youth with ASD. Trial registration: Clinicaltrails.gov NCT00453180

Original languageEnglish (US)
Article number88
JournalMolecular Autism
Volume7
Issue number1
DOIs
StatePublished - Apr 21 2016
Externally publishedYes

Fingerprint

Acetylcysteine
Placebos
Autism Spectrum Disorder
Lost to Follow-Up
Glutathione
Oxidative Stress
Antioxidants
Outcome Assessment (Health Care)
Safety
Therapeutics

Keywords

  • Autism
  • Autism spectrum disorder
  • N-acetylcysteine
  • Oxidative stress
  • Social impairment

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Developmental Neuroscience
  • Developmental Biology
  • Molecular Biology

Cite this

Wink, L. K., Adams, R., Wang, Z., Klaunig, J. E., Plawecki, M. H., Posey, D. J., ... Erickson, C. A. (2016). A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder. Molecular Autism, 7(1), [88]. https://doi.org/10.1186/s13229-016-0088-6

A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder. / Wink, Logan K.; Adams, Ryan; Wang, Zemin; Klaunig, James E.; Plawecki, Martin H.; Posey, David J.; McDougle, Christopher J.; Erickson, Craig A.

In: Molecular Autism, Vol. 7, No. 1, 88, 21.04.2016.

Research output: Contribution to journalArticle

Wink, LK, Adams, R, Wang, Z, Klaunig, JE, Plawecki, MH, Posey, DJ, McDougle, CJ & Erickson, CA 2016, 'A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder', Molecular Autism, vol. 7, no. 1, 88. https://doi.org/10.1186/s13229-016-0088-6
Wink, Logan K. ; Adams, Ryan ; Wang, Zemin ; Klaunig, James E. ; Plawecki, Martin H. ; Posey, David J. ; McDougle, Christopher J. ; Erickson, Craig A. / A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder. In: Molecular Autism. 2016 ; Vol. 7, No. 1.
@article{f38393a399bf492fb0cc4c2bc236fbba,
title = "A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder",
abstract = "Background: Social impairment is a defining feature of autism spectrum disorder (ASD) with no demonstrated effective pharmacologic treatments. The goal of this study was to evaluate efficacy, safety, and tolerability of oral N-acetylcysteine (NAC), an antioxidant whose function overlaps with proposed mechanisms of ASD pathophysiology, targeting core social impairment in youth with ASD. Methods: This study was a 12-week randomized, double-blind, placebo-controlled trial of oral NAC in youth with ASD. Study participants were medically healthy youth age 4 to 12 years with ASD, weighing ≥15 kg, and judged to be moderately ill based on the Clinical Global Impressions Severity scale. The participants were randomized via computer to active drug or placebo in a 1:1 ratio, with the target dose of NAC being 60 mg/kg/day in three divided doses. The primary outcome measure of efficacy was the Clinical Global Impressions Improvement (CGI-I) scale anchored to core social impairment. To investigate the impact of NAC on oxidative stress markers in peripheral blood, venous blood samples were collected at screen and week 12. Results: Thirty-one patients were enrolled (NAC = 16, placebo = 15). Three participants were lost to follow-up, and three left the trial due to adverse effects. The average daily dose of NAC at week 12 was 56.2 mg/kg (SD = 9.7) with dose ranging from 33.6 to 64.3 mg/kg. The frequency of adverse events was so low that comparisons between groups could not be conducted. At week 12, there was no statistically significant difference between the NAC and placebo groups on the CGI-I (p > 0.69) but the glutathione (GSH) level in blood was significantly higher in the NAC group (p <0.05). The oxidative glutathione disulfide (GSSG) level increased in the NAC group, however only at a trend level of significance (p = 0.09). There was no significant difference between the NAC and placebo groups in the GSH/GSSG ratio, DNA strand break and oxidative damage, and blood homocysteine levels at week 12 (ps > 0.16). Conclusions: The results of this trial indicate that NAC treatment was well tolerated, had the expected effect of boosting GSH production, but had no significant impact on social impairment in youth with ASD. Trial registration: Clinicaltrails.gov NCT00453180",
keywords = "Autism, Autism spectrum disorder, N-acetylcysteine, Oxidative stress, Social impairment",
author = "Wink, {Logan K.} and Ryan Adams and Zemin Wang and Klaunig, {James E.} and Plawecki, {Martin H.} and Posey, {David J.} and McDougle, {Christopher J.} and Erickson, {Craig A.}",
year = "2016",
month = "4",
day = "21",
doi = "10.1186/s13229-016-0088-6",
language = "English (US)",
volume = "7",
journal = "Molecular Autism",
issn = "2040-2392",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder

AU - Wink, Logan K.

AU - Adams, Ryan

AU - Wang, Zemin

AU - Klaunig, James E.

AU - Plawecki, Martin H.

AU - Posey, David J.

AU - McDougle, Christopher J.

AU - Erickson, Craig A.

PY - 2016/4/21

Y1 - 2016/4/21

N2 - Background: Social impairment is a defining feature of autism spectrum disorder (ASD) with no demonstrated effective pharmacologic treatments. The goal of this study was to evaluate efficacy, safety, and tolerability of oral N-acetylcysteine (NAC), an antioxidant whose function overlaps with proposed mechanisms of ASD pathophysiology, targeting core social impairment in youth with ASD. Methods: This study was a 12-week randomized, double-blind, placebo-controlled trial of oral NAC in youth with ASD. Study participants were medically healthy youth age 4 to 12 years with ASD, weighing ≥15 kg, and judged to be moderately ill based on the Clinical Global Impressions Severity scale. The participants were randomized via computer to active drug or placebo in a 1:1 ratio, with the target dose of NAC being 60 mg/kg/day in three divided doses. The primary outcome measure of efficacy was the Clinical Global Impressions Improvement (CGI-I) scale anchored to core social impairment. To investigate the impact of NAC on oxidative stress markers in peripheral blood, venous blood samples were collected at screen and week 12. Results: Thirty-one patients were enrolled (NAC = 16, placebo = 15). Three participants were lost to follow-up, and three left the trial due to adverse effects. The average daily dose of NAC at week 12 was 56.2 mg/kg (SD = 9.7) with dose ranging from 33.6 to 64.3 mg/kg. The frequency of adverse events was so low that comparisons between groups could not be conducted. At week 12, there was no statistically significant difference between the NAC and placebo groups on the CGI-I (p > 0.69) but the glutathione (GSH) level in blood was significantly higher in the NAC group (p <0.05). The oxidative glutathione disulfide (GSSG) level increased in the NAC group, however only at a trend level of significance (p = 0.09). There was no significant difference between the NAC and placebo groups in the GSH/GSSG ratio, DNA strand break and oxidative damage, and blood homocysteine levels at week 12 (ps > 0.16). Conclusions: The results of this trial indicate that NAC treatment was well tolerated, had the expected effect of boosting GSH production, but had no significant impact on social impairment in youth with ASD. Trial registration: Clinicaltrails.gov NCT00453180

AB - Background: Social impairment is a defining feature of autism spectrum disorder (ASD) with no demonstrated effective pharmacologic treatments. The goal of this study was to evaluate efficacy, safety, and tolerability of oral N-acetylcysteine (NAC), an antioxidant whose function overlaps with proposed mechanisms of ASD pathophysiology, targeting core social impairment in youth with ASD. Methods: This study was a 12-week randomized, double-blind, placebo-controlled trial of oral NAC in youth with ASD. Study participants were medically healthy youth age 4 to 12 years with ASD, weighing ≥15 kg, and judged to be moderately ill based on the Clinical Global Impressions Severity scale. The participants were randomized via computer to active drug or placebo in a 1:1 ratio, with the target dose of NAC being 60 mg/kg/day in three divided doses. The primary outcome measure of efficacy was the Clinical Global Impressions Improvement (CGI-I) scale anchored to core social impairment. To investigate the impact of NAC on oxidative stress markers in peripheral blood, venous blood samples were collected at screen and week 12. Results: Thirty-one patients were enrolled (NAC = 16, placebo = 15). Three participants were lost to follow-up, and three left the trial due to adverse effects. The average daily dose of NAC at week 12 was 56.2 mg/kg (SD = 9.7) with dose ranging from 33.6 to 64.3 mg/kg. The frequency of adverse events was so low that comparisons between groups could not be conducted. At week 12, there was no statistically significant difference between the NAC and placebo groups on the CGI-I (p > 0.69) but the glutathione (GSH) level in blood was significantly higher in the NAC group (p <0.05). The oxidative glutathione disulfide (GSSG) level increased in the NAC group, however only at a trend level of significance (p = 0.09). There was no significant difference between the NAC and placebo groups in the GSH/GSSG ratio, DNA strand break and oxidative damage, and blood homocysteine levels at week 12 (ps > 0.16). Conclusions: The results of this trial indicate that NAC treatment was well tolerated, had the expected effect of boosting GSH production, but had no significant impact on social impairment in youth with ASD. Trial registration: Clinicaltrails.gov NCT00453180

KW - Autism

KW - Autism spectrum disorder

KW - N-acetylcysteine

KW - Oxidative stress

KW - Social impairment

UR - http://www.scopus.com/inward/record.url?scp=84966297504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84966297504&partnerID=8YFLogxK

U2 - 10.1186/s13229-016-0088-6

DO - 10.1186/s13229-016-0088-6

M3 - Article

AN - SCOPUS:84966297504

VL - 7

JO - Molecular Autism

JF - Molecular Autism

SN - 2040-2392

IS - 1

M1 - 88

ER -