Nicotinic Cholinergic Modulation as a Novel Treatment Strategy for Aggression Associated With Autism

Study Overview
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Brief Summary
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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.

Official Title
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Nicotinic Cholinergic Modulation as a Novel Treatment Strategy for Aggression Associated With Autism

Conditions
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Aggression, Autism Spectrum Disorder, Irritability

Intervention / Treatment
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* Drug: Transdermal nicotine
* Other: Transdermal placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transdermal nicotine first, placebo last<br>Subject will receive transdermal nicotine 7 mg daily for 7 days, placebo patch for 7 days, then placebo patch for a final 7 days. | Drug: Transdermal nicotine<br> <br> Other: Transdermal placebo<br> <br> |
| Experimental: Transdermal placebo first, nicotine last<br>Subject will receive transdermal placebo daily for 7 days, placebo patch for another 7 days, then transdermal nicotine 7 mg daily for a final 7 days. | Drug: Transdermal nicotine<br> <br> Other: Transdermal placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and 7 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and 7 days. | 
| 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?. | Baseline and 7 days | 
| 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. | Baseline and one week | 
| 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). | Baseline and day 7 | 
| Nightly Sleep Quality | Caregivers rated nightly sleep quality from 0 (worst) to 10 (best). Average rating for each treatment week is compared. | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism spectrum disorder, Aggression, Irritability, Nicotine, Nicotinic acetylcholine receptor, Nicotinic agonist, Adult autism