Combined Effects of Early Behavioral Intervention and Propranolol on ASD

February 28, 2024 updated by: David Beversdorf, University of Missouri-Columbia
The purpose of this study is to explore the effects of propranolol in combination with early intensive behavioral intervention on social interaction, and secondarily on language, anxiety, adaptive behaviors, and global function in children with autism in a double-blinded, placebo-controlled pilot trial.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators' specific aim is to examine the effects of serial doses of propranolol in combination with early intensive behavioral intervention on social interaction, and secondarily on language tasks, anxiety, adaptive behaviors, and global function in children 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 pupillary light reflex and heart rate variability, and whether anxiety predicts treatment response. The investigators' hypothesis is that propranolol will augment the effects of behavioral therapy on social functioning and language abilities. The investigators have demonstrated benefits of propranolol on social functioning and language in previous single-dose studies in adults and adolescents with autism. The investigators also predict that those with the greatest degree of autonomic dysregulation will demonstrate the greatest benefit from the drug.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 10 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of autism spectrum disorder (ASD), defined in this study by the DSM-V criteria plus Autism Diagnostic Observation Schedule (ADOS) criteria for Autism.
  • Aged 3-8
  • Participants must also be enrolled in an early behavioral intervention program at the Thompson Center or another institution in Missouri for the duration of the study.

Exclusion Criteria:

  • Non-autism learning disability (e.g. dyslexia)
  • Major psychiatric diagnosis (e.g. major depression, schizophrenia, bipolar disorder)
  • Other neurological diagnosis
  • Major head trauma
  • Any of the following exclusionary criteria related to propranolol (diabetes, reactive airway/pulmonary disease, thyroid disease, bradyarrhythmias, unexplained syncope, narrow angle glaucoma, known hypersensitivity/adverse reaction to beta-blockers, potentially interacting drugs, underweight < 15 kg)
  • Any of the following exclusionary criteria related to the use of electrocardiogram (history of rash from adhesives)
  • Any of the following exclusionary criteria related to the pupillary reflex measurement (uncorrectable visual acuity impairment).
  • Participants with a heart rate of less than 60 or a systolic blood pressure of less than 75 at the outset of the study will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Propranolol arm
Propranolol will be administered in the form of a liquid dose via oral syringe by the participants' parent/caregiver an hour before each EIBI session. To minimize risk, the bodyweight adjusted minimum dose of propranolol used safely for test anxiety in healthy adults (10mg) will be used: participants weighing > 30 kg will be given 4 mg, participants weighing 22.5 - 30 kg will be given 3 mg, participants weighing 15 - 22.5 kg will be given 2 mg. Participants weighing < 15 kg will be excluded for safety reasons.
Drug: Propranolol
Participant will receive Propranolol prior to each EIBI session
Other Names:
  • Inderal
Placebo Comparator: Placebo arm
Placebo will be administered in the form of a liquid dose via oral syringe by the participants' parent/caregiver an hour before each EIBI session.The same bodyweight adjusted doses specified in the propranolol arm will be used for this arm.
Drug: Placebo
Participant will receive placebo prior to each EIBI session

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in General Social Outcome Measure (GSOM)
Time Frame: Week 12
The GSOM is a brief evaluation tool that measures a participant's level of social functioning and how it changes with intervention. There GSOM includes 4 different tasks: conversational reciprocity, ability to recognize facial expressions, social problem solving, affect demonstration, and emotional perspective taking. The experimenter administers each component of the GSOM to the participant and then scores their responses according to a pre-determined scoring rubric. Each component is scored on a 1-5 or 0 - 2 scale, with higher total scores indicating better social functioning. A video camera will be used to record the participant's behavior during GSOM administration for the purposes of having two independent raters score the tasks after the study session is complete. A camera will also be used during the affect demonstration task of the GSOM. The overall score is used. The range is 6-132, with higher scores being better.
Week 12
Change in Social Responsiveness Scale (SRS)
Time Frame: Week 12
This 65-item, parent-report measure asks questions about a participants' social awareness, social information processing, capacity for reciprocal social responses, social anxiety or avoidance, and characteristic autistic preoccupations or traits. The total score is used with a range of 0-195, with lower scores being better.
Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Preschool Anxiety Scale (PAS)
Time Frame: Week 12
To assess anxiety, the PAS will be completed by the parents/caregivers of participants. This self-report measure yields a total score in addition to six subscales (separation anxiety, social phobia, obsessive compulsive, panic/agoraphobia, physical injury fears, and generalized anxiety). The overall score is used. Range is 0-112 with lower score meaning less anxiety.
Week 12
Change in Aberrant Behavior Checklist (ABC)
Time Frame: Week 12
To assess overall behavioral disturbances, a parent/caregiver of the participants will complete ABC. This 58-item questionnaire is a well validated, reliable, and widely used assessment tool for interventions for a range of cognitive disorders. The full score is used, with a range of 0-174, with higher scores meaning more behaviors.
Week 12
Change in Vineland Adaptive Behavior Scales-II (VABS)
Time Frame: Week 12
To assess overall adaptive functioning, the VABS will be administered in the form of a structured interview with the parent/caregiver. The VABS is a well validated assessment used for the full range of our subjects' ages and yields standard scores in Communication, Daily Living Skills, Socialization, and Motor Skills. VABS scores for Socialization will be monitored in this study. The range is 20-160 with higher scores better.
Week 12
Change in Autism Impact Measure (AIM)
Time Frame: Week 12
The AIM will be administered to assess the frequency and impact of a participant's ASD-related symptoms. A parent/caregiver is asked a series of 41 questions regarding the frequency and the impact, or interference resulting from, a series of autism-associated behaviors. Peer interaction from the AIM is the primary domain obtained from this measure. For this domain the range is 0 to 40, with higher numbers more severe.
Week 12
Change in Preschool Language Scale (PLS):
Time Frame: Week 12
To evaluate language, we will administer the PLS, which has been developed for use in younger children (birth through age 7), and is appropriate for children of all ability levels, including nonverbal children. This play-based, interactive assessment is designed to assess receptive and expressive language skills and their change over time. The range is 50-150 with higher scores being better.
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Missouri-Columbia

Collaborators

Autism Science Foundation

Investigators

  • Principal Investigator: David Q Beversdorf, MD, University of Missouri-Columbia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2015

Primary Completion (Actual)

November 1, 2022

Study Completion (Actual)

November 1, 2022

Study Registration Dates

First Submitted

April 16, 2015

First Submitted That Met QC Criteria

April 22, 2015

First Posted (Estimated)

April 28, 2015

Study Record Updates

Last Update Posted (Actual)

March 4, 2024

Last Update Submitted That Met QC Criteria

February 28, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2001935

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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