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

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/orseverely disruptive or destructive behavior, leading to safety concerns or seriousimpact of the quality of life, at least weekly over the past 2 months beforescreening.

• Score in the ASD range on the Autism Diagnostic Observation Schedule conducted atthe 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 aboveat 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 5hours/week with the participant, and can, in the opinion of the investigator,provide a reliable report on the participant's behaviors, symptoms, and complete orsupervise at-home safety monitoring and other assessments required during the study

• Participants of childbearing potential who are sexually active must agree topractice effective contraception from time of screening through 30 days after theirlast dose of study drug. Effective contraception is the use of two methods ofcontraception: 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 toconsent in English and complete study related form in English.

Exclusion Criteria:

• Those who are unable to provide informed consent and have no parent/guardian/legallyauthorized representative to provide informed consent for study enrollment

• Change in psychotropic medication or behavioral intervention (except when caused byvocational, habilitation, or school schedule) within two months beforerandomization.

• 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 becontraindicated, as determined by consulting cardiologist (such as AV block, sicksinus syndrome, valvular pathologies, cardiomyopathies, or vascular disease).

• Uncontrolled seizure disorder (a seizure within the past year and/or changes inseizure medication in the previous six months).

• Diabetes mellitus

• History of lactose intolerance that requires the potential participant to abstainfrom 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 bloodtesting 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, alphablockers, reserpine, inotropic agents (epinephrine), isoproterenol and dobutamine,nonsteroidal anti-inflammatory drugs (indomethacin), antidepressants (MAOinhibitors, tricyclics), anesthetic agents (methoxyflurane, trichloroethylene),warfarin, neuroleptics (haloperidol), thyroxine, alcohol

• Any other medical disorder or medication which would contraindicate the use ofpropranolol.

• Is judged to be inappropriate for the study for any reason by the Investigator

• Has recently participated in another investigational medication study or devicestudy within last 3 months

• Participant is unable to complete blood pressure or ECG safety assessments

• If female, is pregnant or breastfeeding.