Autism Spectrum Disorder, Aggression, Irritability
Conditions
Keywords
Autism spectrum disorder, Aggression, Irritability, Nicotine, Nicotinic acetylcholine receptor, Nicotinic agonist, Adult autism
Brief summary
Some individuals with autism spectrum disorders (ASD) also demonstrate irritability or aggression, which can interfere with functioning. The purpose of this pilot study is to test whether transdermal nicotine is effective for irritability and/or aggression in adults with ASD using a double-blind, placebo-controlled clinical trial. Subjects will participate in three visits. At the first visit, subjects are screened for eligibility and enrolled. Baseline measures include rating scales and a frustrative computerized task. They will then wear seven days of transdermal nicotine or placebo. Visit two is on day seven and the study measures are repeated, vital signs and side effects monitored. Subjects will return for a third and final visit on day 21 to repeat the study measures performed during visit two.
Interventions
OTHERTransdermal placebo
Sponsors
Autism Speaks
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18-60 * Gender: All * Language: Communicative in English * Participants with a prior diagnosis of DSM-5 ASD at some point in their lifetime OR a DSM-4 diagnosis of Autism OR a DSM-4 diagnosis of Asperger's syndrome OR a DSM-4 diagnosis of Pervasive Developmental Disorder Not Otherwise Specified. * Symptoms of irritability, agitation or aggression as reported by parent and/or participant * Aberrant behavior checklist - Irritability Subscale (ABC-I) score of 16 or higher * No changes in psychotropic medications within the past 14 days. * Either lives with a primary caregiver or closely engaged with a primary caregiver who interacts with the patient daily * BMI \> 17.5 and \< 45
Exclusion criteria
* Age \< 18 or \> 60 * BMI \< 17.5 or \> 45 * Currently using tobacco or any nicotine products (transdermal, gum, e-cigarettes) * Changes in psychotropic medication management within the past 14 days * Previous allergy to transdermal patches * Patients with heart rate \> 100 or \< 50 or known history of cardiac rhythm abnormalities * Systolic blood pressure \> 150 or \< 95; diastolic blood pressure \> 90 or \< 50 * No symptoms of irritability, agitation, or aggression as reported by parent and/or participant * ABC-I score of less than 16 * No primary caregiver, or primary caregiver unable to assist with rating scales
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Aberrant Behavior Checklist Irritability Subscale (ABC-I) | Baseline and 7 days. | Aberrant Behavior Checklist (ABC) measures symptom subscales for individuals with neurodevelopmental disorders. The ABC-irritability subscale measures irritability and related symptoms and the subscale score range is 0 (least symptomatic) to 45 (most symptomatic). The ABC is completed by parents/caregivers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Social Responsiveness Scale-Adults (SRS-A) | Baseline and 7 days. | The Social Responsiveness Scale (SRS) - 2 quantifies impairments in social behaviors seen in autism spectrum disorder and related conditions and their severity. The version used in this study is completed by parents/caregivers. The raw score range is 0 (unaffected) to \> 134 (extremely affected). The ABC is completed by parents/caregivers. |
| Change in Qualitative Description of Irritability and Aggression Symptoms | Baseline and 7 days | Brief qualitative reports of the patient's subjective experience will be recorded by asking In what ways did you find the patch helpful or harmful during the past week, if at all?. |
| Change in Frustration and Irritability Ratings During Frustration-induction Go-NoGo Task | Baseline and one week | Subjects will perform a computerized frustration-induction task and complete a rating scale of irritability and frustration levels. |
| Change in State/Trait Anxiety Inventory (STAI) Score | Baseline and day 7 | The State-Trait Anxiety Inventory (STAI) is a measure of trait and state anxiety. It ranges from a score of 20 (least affected) to 80 (most affected). |
| Nightly Sleep Quality | Day 7 | Caregivers rated nightly sleep quality from 0 (worst) to 10 (best). Average rating for each treatment week is compared. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants randomized to receive either transdermal nicotine or placebo | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (7 Days) | Protocol Violation | 1 | 0 |
| Second Intervention (7 Days) | Protocol Violation | 2 | 0 |
Baseline characteristics
| Characteristic | All Study Participants | — |
|---|---|---|
| Aberrant Behavior Checklist-Hyperactivity | 26 units on a scale STANDARD_DEVIATION 11 | — |
| Aberrant Behavior Checklist-Inappropriate speech | 6 units on a scale STANDARD_DEVIATION 4 | — |
| Aberrant Behavior Checklist-Irritability | 25 units on a scale STANDARD_DEVIATION 8 | — |
| Aberrant Behavior Checklist-Lethargy/Social withdrawal | 20 units on a scale STANDARD_DEVIATION 13 | — |
| Aberrant Behavior Checklist-Stereotypic behavior | 9 units on a scale STANDARD_DEVIATION 7 | — |
| Age, Continuous | 24 years STANDARD_DEVIATION 3 | — |
| Number on antipsychotic medication | 5 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 7 Participants | — |
| Sex: Female, Male Female | 1 Participants | — |
| Sex: Female, Male Male | 6 Participants | — |
| Social Responsiveness Scale-2 | 177 units on a scale STANDARD_DEVIATION 25 | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 0 / 7 | 1 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
Change From Baseline in Aberrant Behavior Checklist Irritability Subscale (ABC-I)
Aberrant Behavior Checklist (ABC) measures symptom subscales for individuals with neurodevelopmental disorders. The ABC-irritability subscale measures irritability and related symptoms and the subscale score range is 0 (least symptomatic) to 45 (most symptomatic). The ABC is completed by parents/caregivers.
Time frame: Baseline and 7 days.
Population: All participants who completing all study visits and for which ratings scales were completed in accordance with study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine | Change From Baseline in Aberrant Behavior Checklist Irritability Subscale (ABC-I) | -12 units on a scale | Standard Deviation 3 |
| Placebo | Change From Baseline in Aberrant Behavior Checklist Irritability Subscale (ABC-I) | -7 units on a scale | Standard Deviation 8 |
p-value: 0.44Wilcoxon (Mann-Whitney)
Secondary
Change in Frustration and Irritability Ratings During Frustration-induction Go-NoGo Task
Subjects will perform a computerized frustration-induction task and complete a rating scale of irritability and frustration levels.
Time frame: Baseline and one week
Population: Data were not collected.
Secondary
Change in Qualitative Description of Irritability and Aggression Symptoms
Brief qualitative reports of the patient's subjective experience will be recorded by asking In what ways did you find the patch helpful or harmful during the past week, if at all?.
Time frame: Baseline and 7 days
Population: Data were not collected.
Secondary
Change in Social Responsiveness Scale-Adults (SRS-A)
The Social Responsiveness Scale (SRS) - 2 quantifies impairments in social behaviors seen in autism spectrum disorder and related conditions and their severity. The version used in this study is completed by parents/caregivers. The raw score range is 0 (unaffected) to \> 134 (extremely affected). The ABC is completed by parents/caregivers.
Time frame: Baseline and 7 days.
Population: All participants completing all study visits and for which ratings scales were completed in accordance with study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine | Change in Social Responsiveness Scale-Adults (SRS-A) | -1 units on a scale | Standard Deviation 25 |
| Placebo | Change in Social Responsiveness Scale-Adults (SRS-A) | -15 units on a scale | Standard Deviation 23 |
p-value: 0.38Wilcoxon (Mann-Whitney)
Secondary
Change in State/Trait Anxiety Inventory (STAI) Score
The State-Trait Anxiety Inventory (STAI) is a measure of trait and state anxiety. It ranges from a score of 20 (least affected) to 80 (most affected).
Time frame: Baseline and day 7
Population: Data were not collected.
Secondary
Nightly Sleep Quality
Caregivers rated nightly sleep quality from 0 (worst) to 10 (best). Average rating for each treatment week is compared.
Time frame: Day 7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine | Nightly Sleep Quality | 10 units on a scale | Standard Deviation 0.2 |
| Placebo | Nightly Sleep Quality | 9 units on a scale | Standard Deviation 2 |
p-value: 0.13Wilcoxon (Mann-Whitney)
Post Hoc
Aberrant Behavior Checklist - Hyperactivity Subscale Change From Baseline
Aberrant Behavior Checklist (ABC) measures symptom subscales for individuals with neurodevelopmental disorders. The ABC-hyperactivity subscale measures hyperactivity and related symptoms and the subscale score range is 0 (least symptomatic) to 48 (most symptomatic). The ABC is completed by parents/caregivers.
Time frame: Baseline and 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine | Aberrant Behavior Checklist - Hyperactivity Subscale Change From Baseline | -7 units on a scale | Standard Deviation 6 |
| Placebo | Aberrant Behavior Checklist - Hyperactivity Subscale Change From Baseline | -6 units on a scale | Standard Deviation 6 |
p-value: 1Wilcoxon (Mann-Whitney)
Post Hoc
Aberrant Behavior Checklist - Inappropriate Speech Subscale Change From Baseline
Aberrant Behavior Checklist (ABC) measures symptom subscales for individuals with neurodevelopmental disorders. The ABC-Inappropriate speech subscale measures Inappropriate speech and related symptoms and the subscale score range is 0 (least symptomatic) to 12 (most symptomatic). The ABC is completed by parents/caregivers.
Time frame: Baseline and 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine | Aberrant Behavior Checklist - Inappropriate Speech Subscale Change From Baseline | -1 units on a scale | Standard Deviation 2 |
| Placebo | Aberrant Behavior Checklist - Inappropriate Speech Subscale Change From Baseline | 0.2 units on a scale | Standard Deviation 0.8 |
p-value: 0.25Wilcoxon (Mann-Whitney)
Post Hoc
Aberrant Behavior Checklist - Lethargy/Social Withdrawal Subscale Change From Baseline
Aberrant Behavior Checklist (ABC) measures symptom subscales for individuals with neurodevelopmental disorders. The ABC-lethargy/social withdrawal subscale measures lethargy/social withdrawal and related symptoms and the subscale score range is 0 (least symptomatic) to 48 (most symptomatic). The ABC is completed by parents/caregivers.
Time frame: Baseline and 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine | Aberrant Behavior Checklist - Lethargy/Social Withdrawal Subscale Change From Baseline | -2 units on a scale | Standard Deviation 3 |
| Placebo | Aberrant Behavior Checklist - Lethargy/Social Withdrawal Subscale Change From Baseline | -7 units on a scale | Standard Deviation 4 |
p-value: 0.13Wilcoxon (Mann-Whitney)
Post Hoc
Aberrant Behavior Checklist - Stereotypic Behavior Subscale Change From Baseline
Aberrant Behavior Checklist (ABC) measures symptom subscales for individuals with neurodevelopmental disorders. The ABC-stereotypic behavior subscale measures stereotypic behaviors and related symptoms and the subscale score range is 0 (least symptomatic) to 21 (most symptomatic). The ABC is completed by parents/caregivers.
Time frame: Baseline and 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine | Aberrant Behavior Checklist - Stereotypic Behavior Subscale Change From Baseline | -2 units on a scale | Standard Deviation 3 |
| Placebo | Aberrant Behavior Checklist - Stereotypic Behavior Subscale Change From Baseline | -4 units on a scale | Standard Deviation 4 |
p-value: 0.5Wilcoxon (Mann-Whitney)
Post Hoc
Global Aggressive Behavior Improvement
Caregivers asked which treatment week showed the greatest improvement in aggressive or irritable behavior
Time frame: Baseline and 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nicotine | Global Aggressive Behavior Improvement | 4 Participants |
| Placebo | Global Aggressive Behavior Improvement | 2 Participants |
p-value: 0.69Binomial test