Propranolol for Aggression, Self-Injury, and Severe Disruptive Behavior in Adolescents and Adults With Autism

NCT07091279 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: NYSPI2024-50AR230160
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn if propranolol can help reduce challenging behaviors associated with Autism Spectrum Disorder, including aggression, self-injury, and severe disruptive behaviors. Participants will be randomly assigned to receive either propranolol or a placebo (a look-alike substance that contains no drug) daily for 12 weeks. After the 12 weeks, all participants will have the opportunity to receive propranolol for an additional 12 weeks.

Conditions

Autism Spectrum Disorder; Challenging Behaviour; Aggression; Severe Disruptive Behaviour Disorders; Self-injury

Keywords

autism; autism spectrum disorder; propranolol; severe disruptive behavior; aggression; challenging behavior; self-injury; randomized clinical trial; RCT; high dose propranolol; open label

Outcome Measures

Primary Outcomes (1)

• Incidence of safety concerns and side effects associated with high-dose propranolol, including changes in blood pressure, pulse, and occurrence of dysrhythmias.

  Any participant reported side effects or adverse events will be monitored through weekly medical monitoring visits with the study safety physician. Participants will complete blinded home monitoring of blood pressure and pulse on the first three days each dosing week (baseline through end of treatment phase at 12 weeks), and pre- and post-intervention Holter monitoring will be completed for dysrhythmias (at screening and week 6)

  From baseline through end of treatment phase at 12 weeks

Secondary Outcomes (1)

• Evaluate propranolol for the treatment of severe behaviors in autistic adolescents and adults

  Every 2 weeks from baseline through the end of the treatment phase at 12 weeks

Other Outcomes (1)

• To test whether those with a functional explanation for severe behaviors will respond to propranolol similarly to those with less evidence of functionally based behavior.

  Every 4 weeks from baseline through the end of the treatment phase at 12 weeks

Study Arms (2)

Propranolol

EXPERIMENTAL

Propranolol, oral, starting at 30 mg/day (10 mg TID), titrated weekly based on tolerability to a maximum of 600 mg/day (200 mg TID) by Week 8. Participants will remain on their highest tolerated dose for an additional 4 weeks.

Drug: Propranolol

Placebo

PLACEBO COMPARATOR

Participants will receive oral placebo tablets matched in appearance and dosing schedule to Propranolol. The dose will be titrated weekly in parallel with the experimental arm, and participants will remain on the highest tolerated dose for an additional 4 weeks.

Drug: Placebo

Interventions

Propranolol DRUG

Propranolol, oral, titrated in weekly increments from 10 mg TID to a maximum of 200 mg TID (total daily dose: 30 mg to 600 mg at 8 weeks), based on tolerability. Participants will continue at the highest tolerated dose for additional 4 weeks. Target doses: 10 mg, 40 mg, 80 mg, 120 mg, 160 mg, 200 mg TID.

Propranolol

Placebo DRUG

Placebo for Propranolol

Placebo

Eligibility Criteria

• Age: 12 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age between 12-40 years.
• Clinical best-estimate diagnosis of autism spectrum disorder
• Occurrence of severe challenging behaviors, such as aggression, self-injury, and/or severely disruptive or destructive behavior, leading to safety concerns or serious impact of the quality of life, at least weekly over the past 2 months before screening.
• Score in the ASD range on the Autism Diagnostic Observation Schedule conducted at the time of study entry or in the past 5 years
• Clinical Global Impression Severity scale (CGI-S) score of 4 or above at Baseline
• Aberrant Behavior Checklist-2 Irritability/Agitation Subscale Score of 18 or above at Screening.
• A resting pulse of greater than 60 and a resting blood pressure of greater than 100/60.
• Participant must have a designated study partner who spends a minimum of 5 hours/week with the participant, and can, in the opinion of the investigator, provide a reliable report on the participant's behaviors, symptoms, and complete or supervise at-home safety monitoring and other assessments required during the study
• Participants of childbearing potential who are sexually active must agree to practice effective contraception from time of screening through 30 days after their last dose of study drug. Effective contraception is the use of two methods of contraception: hormonal contraceptives or intrauterine device and barrier (i.e., condoms, diaphragm, or cervical cap).
• Participant must be able to fully swallow study medication capsule.
• English must be primary language for participant. Study partner must be able to consent in English and complete study related form in English.

You may not qualify if:

• Those who are unable to provide informed consent and have no parent/guardian/legally authorized representative to provide informed consent for study enrollment
• Change in psychotropic medication or behavioral intervention (except when caused by vocational, habilitation, or school schedule) within two months before randomization.
• Asthma or history of any disorder involving bronchoconstriction in the past 5 years.
• Cardiovascular history in which the use of propranolol at high doses would be contraindicated, as determined by consulting cardiologist (such as AV block, sick sinus syndrome, valvular pathologies, cardiomyopathies, or vascular disease).
• Uncontrolled seizure disorder (a seizure within the past year and/or changes in seizure medication in the previous six months).
• Diabetes mellitus
• History of lactose intolerance that requires the potential participant to abstain from all dairy products or to take lactase supplements.
• Medical history of renal or hepatic impairment.
• Medical history of hypoglycemia
• Inability to provide blood testing when there is a medical indication for blood testing to allow clinical safety determination by the study safety physician
• Depressive episode currently or within the previous six months
• History of allergy or adverse reaction to propranolol or another beta-blocker
• Current use of any of the following: propafenone, quinidine, amiodarone, lidocaine, digitalis glycosides, calcium channel blockers, ACE inhibitors, clonidine, alpha blockers, reserpine, inotropic agents (epinephrine), isoproterenol and dobutamine, nonsteroidal anti-inflammatory drugs (indomethacin), antidepressants (MAO inhibitors, tricyclics), anesthetic agents (methoxyflurane, trichloroethylene), warfarin, neuroleptics (haloperidol), thyroxine, alcohol
• Any other medical disorder or medication which would contraindicate the use of propranolol.
• Is judged to be inappropriate for the study for any reason by the Investigator

Sponsors & Collaborators

• Jeremy Veenstra-vanderweele: lead
• United States Department of Defense: collaborator
• New York State Institute for Basic Research: collaborator

Study Sites (2)

New York State Institute for Basic Research (IBR)

Staten Island, New York, 10314, United States

RECRUITING

Center for Autism and the Developing Brain

White Plains, New York, 10605, United States

RECRUITING

MeSH Terms

Conditions

Autism Spectrum Disorder; Aggression; Self-Injurious Behavior; Autistic Disorder; Problem Behavior

Interventions

Propranolol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jeremy Veenstra-VanderWeele, MD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

• Eric London, MD

  New York State Institute for Basic Research (IBR)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Suvekcha Bhattachan, MA

CONTACT

914-997-5587; suvekcha.bhattachan@nyspi.columbia.edu

Alyssa Verdes, BA

CONTACT

914-997-5532; alyssa.verdes@nyspi.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 7, 2025
• First Posted: July 29, 2025
• Study Start: January 30, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Access Criteria: Only approved researchers with NDA access will be able to use the data

Locations

US (2)