Propranolol for Challenging Behaviors in Autism

NCT04047355 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: Pro20170001942CAUT17 APL025
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Severe challenging behaviors such as aggression and self-injury can cause significant morbidity and decrease the quality of life for individuals with Autism Spectrum Disorders (ASD). There are only two medications (Risperdal and Abilify) rigorously studied and FDA-approved for the treatment of irritability in individuals with ASD. These medications are not always successful and have many short and long-term side effects. Well-designed studies demonstrating efficacy and safety of alternative medication treatment choices are needed. There is preliminary evidence that high-dose propranolol can be effective in individuals with ASD who display severe aggression and have not responded to antipsychotics or mood stabilizers. Concerns regarding the safety of high dose propranolol have limited its clinical application. Well-designed clinical trials demonstrating the efficacy and safety of high dose propranolol will have significant effects on clinical practice and improve the physical and behavioral quality of life for an underserved subset of individuals with ASD. This study will pilot the safety and efficacy of high dose propranolol. The investigators will randomly assign participants to either propranolol or to placebo later crossing each participant over to the other group. As propranolol can cause changes in blood pressure and heart function, each participant will complete initial comprehensive testing to monitor cardiac safety throughout the study. The investigators will be utilizing telemedicine and computer based telemetry to minimize the burden of office visits on the individual and family.

Conditions

Autism Spectrum Disorder; Developmental Disability; Aggression; Self-Injurious Behavior; Challenging Behavior

Keywords

Propranolol; Beta Blocker; Psychopharmacology; Inderal

Outcome Measures

Primary Outcomes (1)

• Aberrant Behavior Checklist--Community (ABC-C) Irritability Subscale Scores

  The Aberrant Behavior Checklist--Community (ABC-C) is a behavior checklist that measures drug and other treatment effects in people with intellectual and developmental disabilities. It is made up of five subscales, including Irritability, Lethargy, Inappropriate Speech, Hyperactivity, and Stereotypy based on 58 items that describe various behavioral problems. Each item is scored on a Likert scale: 1 = not at all a problem, to 3 = problem is severe in degree. The Irritability Subscale served as the primary dependent measure. The minimum score on the Irritability Subscale is 0 and the maximum score is 45. Lower scores represent better outcome.

  Titration schedule varied based on individual response; it was not predetermined. On average, Placebo was 8 wks and Propranolol was 11 wks, including titration. The last Baseline score and the last scores from Placebo and Propranolol phases were analyzed.

Secondary Outcomes (1)

• Clinical Global Impression Improvement (CGI-I) Scale

  Titration schedule varied based on individual response; it was not predetermined. On average, Placebo was 8 wks and Propranolol was 11 wks, including titration. The last Baseline score and the last scores from Placebo and Propranolol phases were analyzed.

Study Arms (2)

Group A: Propranolol first

EXPERIMENTAL

Participants randomly assigned to this group will receive Propranolol first. After the washout period, they will receive Placebo. Propranolol will be given in liquid or pill form.

Drug: Propranolol

Group B: Placebo first

PLACEBO COMPARATOR

Participants randomly assigned to this group will receive Placebo first. After the washout period, they will receive Propranolol. Placebo will look identical to the study drug Propranolol.

Drug: Propranolol

Interventions

Propranolol DRUG

Propranolol is a beta-blocker used to treat high blood pressure, irregular heartbeats, and tremors. It is used after a heart attack and to prevent migraine headaches and chest pain. It is also used off-label for anxiety and PTSD.

Also known as: Inderal

Group A: Propranolol first; Group B: Placebo first

Eligibility Criteria

• Age: 12 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males and females between the ages of 12-30 years and is a resident in the state of New Jersey.
• Diagnosis of autism conducted by a clinician with confirmation using the Autism Diagnostic Observation Schedule (ADOS) or the Social Communication Questionnaire (SCQ).
• At least one of the following challenging behaviors.
• Self-injurious behaviors (e.g., hitting one's self, head banging or banging of other body parts causing some degree of tissue damage);
• Physical aggression towards others (e.g., hitting, kicking, pushing, or throwing objects at others);
• Disruptive behaviors including property destruction during anger episodes, excessive screaming which interferes with functioning; and
• The challenging behaviors are generally (but not necessarily exclusively) associated with a congruent affect (i.e. anger or rage when aggressing) as determined by the study psychiatrist.
• Pharmacologic treatment with at least two psychotropic including one antipsychotic medication has yielded inadequate outcome (partial improvement on one or more medications is acceptable for the study).
• Clinical Global Impression Severity scale score of 6 or 7.
• Aberrant Behavior Checklist--Community Irritability scale score at or above 18.
• Medical and cardiac clearance.

You may not qualify if:

• Asthma or any history of asthma or any disorder involving bronchoconstriction.
• Cardiac Diseases in which the use of propranolol at high doses would be contraindicated.
• Uncontrolled Seizure disorder (participant had a seizure within the past year and/or changes in seizure medication in the previous six months).
• Diabetes or a history of ketoacidosis.
• Any other medical disorder or medication which would contraindicate the use of propranolol.
• History of allergy or adverse reaction to propranolol.
• Pregnancy.

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• New Jersey Governor's Council for Medical Research and Treatment of Autism: collaborator
• New York State Institute for Basic Research: collaborator

Study Sites (1)

Department of Pediatrics, Division of Pediatric Neurology, Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

MeSH Terms

Conditions

Autism Spectrum Disorder; Developmental Disabilities; Aggression; Self-Injurious Behavior

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Social Behavior

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: J. Helen Yoo, Ph.D.
• Organization: New York State Institute for Basic Research

jhelen.yoo@opwdd.ny.gov

718-494-5295

Study Officials

• Barbie Zimmerman-Bier, M.D.

  Rutgers, The State University of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: July 12, 2019
• First Posted: August 6, 2019
• Study Start: February 11, 2021
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2023
• Last Updated: June 4, 2025
• Results First Posted: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)