Clinical trial NCT04047355: Propranolol for Challenging Behaviors in Autism
Official title: A Pilot/Feasibility Study of the Use of High Dose Propranolol to Treat Severe and Chronic Challenging Behaviors in Adolescents and Adults With Autism Spectrum Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism Spectrum Disorder
Developmental Disability
Aggression
Self-Injurious Behavior
Challenging Behavior
Keywords: Propranolol
Beta Blocker
Psychopharmacology
Inderal
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: New Jersey Governor's Council for Medical Research and Treatment of Autism
name: New York State Institute for Basic Research
First posted: 2019-08-06
Enrollment: 8
Sex: ALL
Minimum age (years): 12
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Detailed description: This is a randomized, double blind, placebo controlled crossover study. A complete cardiac exam will be conducted by the pediatric cardiology team at the Robert Wood Johnson Medical School. All participants will remain on their existing, pre-study medication throughout all phases of the study.

Once admitted to the study, a baseline period will begin. During the baseline period, cognitive and adaptive information will be collected. The participant will then be randomly assigned to propranolol (Phase A) or placebo (Phase B). The titration schedule will be flexible and the dose can be held steady for an extended period. Dose reduction to manage side effects are allowed at any time. Each week the family will complete behavioral forms online and meet with the study psychiatrist via telemedicine. Following the initial Phase (A or B), participants will undergo a washout period (whether propranolol or placebo). Then, they will crossover to the other Phase (A or B). Upon completion of the crossover phase, the study blind will be broken. The participants then had the option of enrolling in an open label study.

Eligibility criteria: Inclusion Criteria:

1. Males and females between the ages of 12-30 years and is a resident in the state of New Jersey.
2. Diagnosis of autism conducted by a clinician with confirmation using the Autism Diagnostic Observation Schedule (ADOS) or the Social Communication Questionnaire (SCQ).
3. At least one of the following challenging behaviors.

   1. Self-injurious behaviors (e.g., hitting one's self, head banging or banging of other body parts causing some degree of tissue damage);
   2. Physical aggression towards others (e.g., hitting, kicking, pushing, or throwing objects at others);
   3. Disruptive behaviors including property destruction during anger episodes, excessive screaming which interferes with functioning; and
   4. 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.
4. 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).
5. Clinical Global Impression Severity scale score of 6 or 7.
6. Aberrant Behavior Checklist--Community Irritability scale score at or above 18.
7. Medical and cardiac clearance.

Exclusion Criteria:

1. Asthma or any history of asthma or any disorder involving bronchoconstriction.
2. Cardiac Diseases in which the use of propranolol at high doses would be contraindicated.
3. Uncontrolled Seizure disorder (participant had a seizure within the past year and/or changes in seizure medication in the previous six months).
4. Diabetes or a history of ketoacidosis.
5. Any other medical disorder or medication which would contraindicate the use of propranolol.
6. History of allergy or adverse reaction to propranolol.
7. Pregnancy.
8. Medication exclusions include clonidine/guanfacine / digoxin or other medications affecting blood pressure.

Primary outcomes:
measure: Aberrant Behavior Checklist--Community (ABC-C) Irritability Subscale Scores
timeFrame: 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:
measure: Clinical Global Impression Improvement (CGI-I) Scale
timeFrame: 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.
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Department of Pediatrics, Division of Pediatric Neurology, Robert Wood Johnson Medical School
state: New Jersey
Study officials:
affiliation: Rutgers, The State University of New Jersey
name: Barbie Zimmerman-Bier, M.D.
role: PRINCIPAL_INVESTIGATOR
References: