Propranolol for aggression, self-injury, and severe disruptive behaviors in adolescents and adults with autism

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

This trial will test whether propranolol can reduce aggression, self-injury, and other severe disruptive behaviors in people with autism aged 12 to 40.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 12 Years to 40 Years
• Sex: All
• Sponsor: New York State Psychiatric Institute (other)
• Locations: 2 sites (Staten Island, New York and 1 other locations)
• Trial ID: NCT07091279 on ClinicalTrials.gov

What this trial studies

This randomized, placebo-controlled Phase 2 trial will enroll 60 participants with autism spectrum disorder who have frequent severe challenging behaviors and meet severity thresholds on standardized scales. Participants are randomized to receive either propranolol or placebo for 12 weeks, with an 8-week dose escalation (to a maximum tolerated dose up to 200 mg three times daily) followed by 4 weeks at a steady dose. After the randomized phase, all participants may enter a 12-week open-label extension where they receive propranolol. Safety monitoring includes vital sign criteria at entry and ongoing assessment for tolerability during dose escalation.

Who should consider this trial

Good fit: Ideal candidates are people with a clinical diagnosis of ASD aged 12–40 who have at least weekly severe challenging behaviors and meet the trial's CGI-S and ABC-I/A severity thresholds, can have a study partner, and meet baseline vital-sign criteria.

Not a fit: Patients without frequent severe challenging behaviors, those who do not meet the severity or vital-sign requirements, or those with contraindications or intolerance to beta-blockers are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, propranolol could reduce dangerous or disruptive behaviors and improve safety and quality of life for people with autism.

How similar studies have performed: Small pilot studies and case reports have suggested propranolol might help certain behavioral or social symptoms in autism, but rigorous high-dose randomized evidence for reducing severe aggression is limited.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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
* Has recently participated in another investigational medication study or device study within last 3 months
* Participant is unable to complete blood pressure or ECG safety assessments
* If female, is pregnant or breastfeeding.

Where this trial is running

Staten Island, New York and 1 other locations

• New York State Institute for Basic Research (IBR) — Staten Island, New York, United States (RECRUITING)
• Center for Autism and the Developing Brain — White Plains, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Jeremy Veenstra-VanderWeele, MD — New York State Psychiatric Institute
• Study coordinator: Suvekcha Bhattachan, MA

Conditions: Autism Spectrum Disorder, Challenging Behaviour, Aggression, Severe Disruptive Behaviour Disorders, Self-injury, autism, autism spectrum disorder, propranolol