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

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.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Propranolol; Device: Magnetic Resonance Imaging (MRI); Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65211
      • Thompson Center for Autism & Neurodevelopmental Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 24 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Propanolol and MRI; 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; 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.; Other Names: Inderal; Hemangeol; Innopran; Device: Magnetic Resonance Imaging (MRI); An MRI will be performed on participants aged 15-24 years.
Placebo Comparator: Placebo and MRI; Participants will receive placebo via oral capsule, crushed tablet, or liquid daily. Those aged 15-24 will have an MRI before starting drug.	Device: Magnetic Resonance Imaging (MRI); An MRI will be performed on participants aged 15-24 years.; Drug: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Companion Animal Bonding Scale		Day 1, 6 weeks, 12 weeks
Change in Sympathetic Tone & Anxiety Measurements	Pupillary light reflex, heart rate, heart rate variability, skin conductance, and blood pressure	Day 1, 12 weeks
Changes in salivary cortisol		Day 1, 6 weeks, 12 weeks
Changes in Sensory Over-Responsivity questionnaire		Day 1, 6 weeks, 12 weeks

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: David Q Beversdorf, MD, University of Missouri-Columbia

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): August 1, 2020

Study Registration Dates

• First Submitted: August 15, 2016
• First Submitted That Met QC Criteria: August 17, 2016
• First Posted (Estimate): August 18, 2016

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 7, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: ASD; Autism
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: 2005213