Autism Spectrum Disorder
Conditions
Keywords
Autism
Brief summary
The aim of this study is to investigate if taking a supplement called Glutathione by mouth is safe and practical for children and teenagers with Autism Spectrum Disorder (ASD). The researchers plan to involve 24 individuals with ASD and give them oral Glutathione for 12 weeks.
Detailed description
The goal of the proposed study is to evaluate the safety and feasibility of oral Glutathione in children and adolescents who have Autism Spectrum Disorder. Twenty-four subjects with ASD will receive 12 weeks of oral Glutathione reduced. The hypothesis to be tested is that: Oral Glutathione will be effective in increasing the blood level of Glutathione, which may help to decrease some problem behaviors and irritability in this particular ASD population. The second aim of this study is to evaluate the tolerability of oral Glutathione. The proposed study may provide needed data for future studies aimed at the treatment of aggressive behaviors that can be seen in this patient population.
Interventions
DRUGGlutathione
Giving supplement orally
Sponsors
University of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Boys and girls ages 4-17 * Current diagnosis of Autism Spectrum Disorder as determined by criteria in DSM-5 * Parents of Children ages 4-17 with a current diagnosis of Autism Spectrum Disorder as determined by criteria in DSM-5
Exclusion criteria
* Unstable medical illness or clinically significant abnormalities on physical examination; * History of seizures; * History of Hematological disorders; * Myocardial infarction within 6 months; * Current pregnancy or lactation, or inadequate contraception in girls of childbearing potential; * Current or recent (past 3 months) DSM-5 substance abuse or dependence; * Illegal substance use within 2 weeks of study initiation; * Previous treatment with Glutathione; * Current treatment with N-acetylcysteine, milk thistle, Vitamin C, Vitamin B, Grape Seed Extract, Amino Acids, or Zinc * Current treatment with Dextromethorphan, D-cycloserine, Amantadine, Memantine, Lamotrigine or Riluzole * Asthma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aberrant Child Checklist, Looking at Change in the Subscale of the ABC | baseline and 12 weeks. To clarify, all pre-specified Primary and Secondary Outcome Measures were collected at baseline and the 12-week endpoint only. No intermediate assessments were conducted. | The Aberrant Behavior Checklist (ABC) measures psychiatric symptoms and behavioral disturbances in individuals with IDD across five subscales: Irritability (0-45), Social Withdrawal (0-48), Stereotypic Behavior (0-21), Hyperactivity (0-48), and Inappropriate Speech (0-12). Each subscale score is summed to calculate a total score ranging from 0 to 174. Higher scores indicate worse outcomes, with no specific cutoff values, as the measure is used alongside diagnostic tools like the Autism Diagnostic Observation Schedule (ADOS). The ABC is designed to establish baseline symptoms and monitor changes over time, where a decrease in scores reflects improvement, and an increase indicates worsening symptoms.The Aberrant Behavior Checklist (ABC) consists of five subscales: Irritability (0-45), Lethargy (0-48), Stereotypic Behavior (0-21), Hyperactivity (0-48), and Inappropriate Speech (0-12). Higher scores represent more severe symptoms. The total ABC score ranges from 0 to 174 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Social Responsiveness Scale | We only have the Social Responsiveness Scale measurement at baseline. | The Social Responsiveness Scale, Second Edition (SRS-2) is a 65-item caregiver-rated questionnaire that measures the severity of social impairments associated with autism spectrum disorder (ASD) in children and adolescents (ages 2 years 6 months to 18 years). It assesses five domains: Social Awareness, Social Cognition, Social Communication, Social Motivation, and Restricted Interests and Repetitive Behavior, as well as a Total Score. T-scores typically range from approximately 30 to 90+, with scores capped at 90 in cases of severe impairment. Higher T-scores indicate greater severity of social impairment (worse outcome), while lower T-scores indicate fewer social difficulties (better outcome). Clinically Relevant Thresholds T-score ≤ 59: Within normal limits T-score 60-65: Mild range (borderline, subclinical difficulties) T-score 66-75: Moderate range (clinically significant impairment) T-score ≥ 76: Severe range (marked impairment) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinical Global Impression Scale | At baseline and the end of the trial (12 weeks) | The Clinical Global Impression (CGI) is a clinician-rated instrument developed for use in NIMH-sponsored clinical trials to provide a brief global assessment of illness severity, improvement, and therapeutic efficacy. The three commonly reported CGI scales are: CGI-Severity (CGI-S): Rates current illness severity from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). CGI-Improvement (CGI-I): Rates change in clinical status from baseline on a 7-point scale, ranging from 1 (Very much improved) to 7 (Very much worse). CGI-Efficacy Index (CGI-E): Balances therapeutic efficacy with adverse effects, rated on a 4 × 4 grid, where higher scores reflect minimal efficacy and/or significant side effects. Lower CGI-S and CGI-I scores indicate better outcomes (less illness severity and/or greater improvement). Higher CGI-E scores reflect worse outcomes (limited efficacy and/or significant side effects). Higher CGI-E scores reflect worse outcomes |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Glutathione Oral Supplementation Glutathione will be the only study medication dispensed to subjects for this study. Subjects will be told to take the first dose of study medication after breakfast each day and the second dose in the evening after dinner. The proposed dose range for Glutathione in this study will be 1000mg-3000mg/day based on the subject's weight.
Glutathione: Giving supplement orally | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Glutathione Oral Supplementation |
|---|---|
| Age, Categorical <=18 years | 6 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 14.67 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 1 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Aberrant Child Checklist, Looking at Change in the Subscale of the ABC
The Aberrant Behavior Checklist (ABC) measures psychiatric symptoms and behavioral disturbances in individuals with IDD across five subscales: Irritability (0-45), Social Withdrawal (0-48), Stereotypic Behavior (0-21), Hyperactivity (0-48), and Inappropriate Speech (0-12). Each subscale score is summed to calculate a total score ranging from 0 to 174. Higher scores indicate worse outcomes, with no specific cutoff values, as the measure is used alongside diagnostic tools like the Autism Diagnostic Observation Schedule (ADOS). The ABC is designed to establish baseline symptoms and monitor changes over time, where a decrease in scores reflects improvement, and an increase indicates worsening symptoms.The Aberrant Behavior Checklist (ABC) consists of five subscales: Irritability (0-45), Lethargy (0-48), Stereotypic Behavior (0-21), Hyperactivity (0-48), and Inappropriate Speech (0-12). Higher scores represent more severe symptoms. The total ABC score ranges from 0 to 174
Time frame: baseline and 12 weeks. To clarify, all pre-specified Primary and Secondary Outcome Measures were collected at baseline and the 12-week endpoint only. No intermediate assessments were conducted.
Population: All participants who received at least one dose of oral glutathione and had both baseline and Week 12 (or endpoint) Aberrant Behavior Checklist (ABC) assessments available (n=5). One participant discontinued after 2 weeks due to increased irritability and was excluded from the change analysis
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Glutathione | Aberrant Child Checklist, Looking at Change in the Subscale of the ABC | ABC: Irritability | 18.60 units on a scale |
| Glutathione | Aberrant Child Checklist, Looking at Change in the Subscale of the ABC | ABC: Lethargy | 14.40 units on a scale |
| Glutathione | Aberrant Child Checklist, Looking at Change in the Subscale of the ABC | ABC: Stereotypy | 8.80 units on a scale |
| Glutathione | Aberrant Child Checklist, Looking at Change in the Subscale of the ABC | ABC: Hyperactivity | 14.80 units on a scale |
| Glutathione | Aberrant Child Checklist, Looking at Change in the Subscale of the ABC | ABC: Inappropriate Speech | 6.40 units on a scale |
Comparison: For the analysis of (ABC) scores at baseline and 12 weeks in this single-arm, open-label pilot study (n=6 participants, all with paired data including the early dropout), we use superiority test, This aligns with the study's hypothesis that oral glutathione supplementation would lead to an improvement (i.e., a decrease in ABC scores, indicating reduced irritability). Superiority testing evaluates whether the post-treatment mean (or median) is significantly lower than the baselinep-value: 0.180795% CI: [-6.24, 14.24]Wilcoxon (Mann-Whitney)
Secondary
Social Responsiveness Scale
The Social Responsiveness Scale, Second Edition (SRS-2) is a 65-item caregiver-rated questionnaire that measures the severity of social impairments associated with autism spectrum disorder (ASD) in children and adolescents (ages 2 years 6 months to 18 years). It assesses five domains: Social Awareness, Social Cognition, Social Communication, Social Motivation, and Restricted Interests and Repetitive Behavior, as well as a Total Score. T-scores typically range from approximately 30 to 90+, with scores capped at 90 in cases of severe impairment. Higher T-scores indicate greater severity of social impairment (worse outcome), while lower T-scores indicate fewer social difficulties (better outcome). Clinically Relevant Thresholds T-score ≤ 59: Within normal limits T-score 60-65: Mild range (borderline, subclinical difficulties) T-score 66-75: Moderate range (clinically significant impairment) T-score ≥ 76: Severe range (marked impairment)
Time frame: We only have the Social Responsiveness Scale measurement at baseline.
Population: All participants who were enrolled and completed the baseline Social Responsiveness Scale (SRS) assessment (n=6)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Glutathione | Social Responsiveness Scale | Social Awareness | 75.5 T-score for this instrument. |
| Glutathione | Social Responsiveness Scale | Social Cognition | 85.0 T-score for this instrument. |
| Glutathione | Social Responsiveness Scale | Social Communication | 90.00 T-score for this instrument. |
| Glutathione | Social Responsiveness Scale | Social Motivation | 82.0 T-score for this instrument. |
| Glutathione | Social Responsiveness Scale | Autism Mannerisms | 89.0 T-score for this instrument. |
| Glutathione | Social Responsiveness Scale | Total Severity | 89 T-score for this instrument. |
Post Hoc
CGI-Efficacy Index (CGI-E): Balances Therapeutic Efficacy With Adverse Effects, Rated on a 4 × 4 Grid, Where Higher Scores Reflect Minimal Efficacy and/or Significant Side Effects.
two patients had no therapeutic changes, four had minimal efficacy, five had no side effects, and one dropped out due to significant side effects
Time frame: 12 weeks
Other Pre-specified
Change in Clinical Global Impression Scale
The Clinical Global Impression (CGI) is a clinician-rated instrument developed for use in NIMH-sponsored clinical trials to provide a brief global assessment of illness severity, improvement, and therapeutic efficacy. The three commonly reported CGI scales are: CGI-Severity (CGI-S): Rates current illness severity from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). CGI-Improvement (CGI-I): Rates change in clinical status from baseline on a 7-point scale, ranging from 1 (Very much improved) to 7 (Very much worse). CGI-Efficacy Index (CGI-E): Balances therapeutic efficacy with adverse effects, rated on a 4 × 4 grid, where higher scores reflect minimal efficacy and/or significant side effects. Lower CGI-S and CGI-I scores indicate better outcomes (less illness severity and/or greater improvement). Higher CGI-E scores reflect worse outcomes (limited efficacy and/or significant side effects). Higher CGI-E scores reflect worse outcomes
Time frame: At baseline and the end of the trial (12 weeks)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Glutathione | Change in Clinical Global Impression Scale | Pre-Treatment CGI Severity | 4 score on a scale |
| Glutathione | Change in Clinical Global Impression Scale | Post-Treatment CGI Severity | 4.5 score on a scale |
| Glutathione | Change in Clinical Global Impression Scale | CGI Improvement | 3 score on a scale |
| Glutathione | Change in Clinical Global Impression Scale | Efficacy Index | 9 score on a scale |
Post Hoc
Clinical Global Impression - Improvement Scale: Rates Change in Clinical Status From Baseline on a 7-point Scale, Ranging From 1 (Very Much Improved) to 7 (Very Much Worse).
1 subject scored 4 (no change), four scored 3 (minimally improved), and one scored 6 (much worse).
Time frame: 12 weeks
Post Hoc
Clinical Global Impression - Severity Scale (CGI-S) Range for Participants
Pre-treatment CGI-S ratings ranged from 2 (borderline ill) to 5 (markedly ill). One subject's CGI-S changed from 4 (moderately ill) to 5 (markedly ill); others had no change.
Time frame: 12 weeks