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.
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
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).
Parallel
Propranolol
DrugPropranolol, 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.
Placebo
DrugPlacebo for Propranolol
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)
Evaluate propranolol for the treatment of severe behaviors in autistic adolescents and adults
Assessed using the Aberrant Behavior Checklist-Community (ABC-C) Irritability/Agitation Subscale. The ABC-C is a global behavior checklist that measures drug and other treatment effects in people with 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. The Irritability/Agitation Subscale (15-item questionnaire) will serve as the primary dependent measure. Each item is rated on a 4-point Likert scale, ranging from 0 (not a problem) to 3 (severe problem). The scores will range from minimum value of 0 to maximum value of 45, with higher score indicating worse outcome. The scale will be rated every 2 weeks from baseline to end of treatment phase.
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.
We hypothesize that participants who demonstrate greater environmentally mediated function(s) on the Questions about Behavior Function scale (QABF) scale will benefit less from propranolol. The QABF is an indirect assessment of behavioral function for individuals with developmental disabilities. It contains 25 items. The QABF yields five behavioral function categories: Access to Attention, Escape from Demands, Physical, Access to Tangible, and Nonsocial. Each question is scored with frequency descriptors of Never=0, Rarely=1, Some=2, and Often=3. Subscale scores can range from minimum value of 0 to maximum value of 15, with higher scores indicating a stronger influence of that specific behavioral function in maintaining the challenging behavior. The QABF will be administered every 4 weeks to examine whether challenging behavior serves a specific function and if so, examine whether propranolol potentially changes the function or the strength of those functions.
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Jeremy Veenstra-vanderweele
Lead sponsor
New York State Psychiatric Institute
Sponsor institution
United States Department of Defense
Collaborator
New York State Institute for Basic Research
Collaborator
