Trial of Propranolol in Children and Youth With Autism Spectrum Disorder and Predictors of Response

Study Overview
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Brief Summary
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The purpose of this study is to find out how the brain of people with autism is affected by Propranolol. Propranolol is not FDA approved for the treatment of autism. Propranolol is FDA approved for the treatment of heart conditions such as blood pressure This research is being done because there are currently no drug treatment options for language impairments and social difficulties often experienced by people with autism.

Detailed Description
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The specific aim of this study is to examine the effects of serial doses of propranolol on social interaction, and secondarily on language tasks, anxiety, adaptive behaviors, and global function in high functioning adults and adolescents with autism in a double-blinded, placebo-controlled trial. The investigators will also examine whether response to treatment can be predicted based upon markers of autonomic functioning, such as skin conductance, heart rate variability (HRV), and the pupillary light reflex (PLR), and whether anxiety can predict treatment response. The hypothesis is that social functioning and language abilities will benefit from serial doses of propranolol, and that those with the greatest degree of autonomic dysregulation, or the lowest functional connectivity, will demonstrate the greatest benefit from the drug.

Official Title
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Trial of Propranolol in Children and Youth With Autism Spectrum Disorder and Predictors of Response

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Propranolol
* Drug: Placebo
* Device: Magnetic Resonance Imaging (MRI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Autism Spectrum Disorder diagnosis intelligence quotient (IQ) >= 85 (if aged 15-24), >= 75 (if aged 7-14) Native English speaker Parent or caregiver must older than 18 years and be a native English speaker Exclusion Criteria: Taking Alpha 2 agonists Non-autism learning disorder Other major psychiatric disorders Other neurological disorders Major head trauma Reaction to adhesives Diabetes Reactive airway disease Thyroid disease Bradyarrhythmias Unexplained syncope Pregnancy Possible interacting drugs Underweight (<20kg if aged 7-14 years) Factors affecting ability to have an MRI (if aged 15-24 years)

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 24 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propanolol and MRI<br>Participants will receive propranolol via oral capsule, crushed tablet, or liquid daily. The drug dosage will be titrated slowly to ensure the drug is tolerated well. Those aged 15-24 will have an MRI before starting drug. | Drug: Propranolol<br>* Propanolol will be given on a titration schedule in which participants will begin with small doses (single capsules) of the drug and increase to a larger dosage (divided over 3 capsules) over the course of three weeks. Participants aged 15-24 years will undergo an MRI.<br>* Other names: Innopran;Device: Magnetic Resonance Imaging (MRI)<br>* An MRI will be performed on participants aged 15-24 years.<br>|
| Placebo Comparator: Placebo and MRI<br>Participants will receive placebo via oral capsule, crushed tablet, or liquid daily. Those aged 15-24 will have an MRI before starting drug. | Drug: Placebo<br>* Placebo will be given in the form preferred by the participant and on the same schedule as the propanolol regime. Participants aged 15-24 years will undergo an MRI.<br>Device: Magnetic Resonance Imaging (MRI)<br>* An MRI will be performed on participants aged 15-24 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in General Social Outcomes Measure (GSOM) Assessment |  | Day 1, 6 weeks, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Social Responsiveness Scale (SRS-2) |  | Day 1, 6 weeks, 12 weeks | 
| Change in score on Anagrams test | For those aged 15-24 only | Day 1, 6 weeks, 12 weeks | 
| Change in Semantic fluency test results | For those aged 15-24 only | Day 1, 6 weeks, 12 weeks | 
| Change Clinical Global Impression surveys |  | Day 1, 6 weeks, 12 weeks | 
| Change in Autism Impact Measure (AIM) |  | Day 1, 6 weeks, 12 weeks | 
| Change in Clinical Evaluation of Language Fundamentals (CELF-5) assessment |  | Day 1, 6 weeks, 12 weeks | 
| Change in Vineland Adaptive Behavior Scales (VABS-2) assessment |  | Day 1, 6 weeks, 12 weeks | 
| Change in score on Aberrant Behavior Checklist (ABC) |  | Day 1, 6 weeks, 12 weeks | 
| Change in gastrointestinal symptomology | Rome IV Diagnostic Questionnaire on Pediatric Functional Gastrointestinal Disorders (R4PDQ-child) and Rome IV Diagnostic Questionnaire (R4DQA) for adults | Day 1, 1 week, 2 weeks, 6 weeks, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism, ASD