Autism
Conditions
Brief summary
The purpose of this study is to explore the effects of propranolol in combination with early intensive behavioral intervention on social interaction, and secondarily on language, anxiety, adaptive behaviors, and global function in children with autism in a double-blinded, placebo-controlled pilot trial.
Detailed description
The investigators' specific aim is to examine the effects of serial doses of propranolol in combination with early intensive behavioral intervention on social interaction, and secondarily on language tasks, anxiety, adaptive behaviors, and global function in children with autism in a double-blinded, placebo-controlled trial. The investigators will also examine whether response to treatment can be predicted based upon markers of autonomic functioning, such as pupillary light reflex and heart rate variability, and whether anxiety predicts treatment response. The investigators' hypothesis is that propranolol will augment the effects of behavioral therapy on social functioning and language abilities. The investigators have demonstrated benefits of propranolol on social functioning and language in previous single-dose studies in adults and adolescents with autism. The investigators also predict that those with the greatest degree of autonomic dysregulation will demonstrate the greatest benefit from the drug.
Interventions
DRUGPropranolol
Participant will receive Propranolol prior to each EIBI session
DRUGPlacebo
Participant will receive placebo prior to each EIBI session
Sponsors
Autism Science Foundation
University of Missouri-Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 10 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of autism spectrum disorder (ASD), defined in this study by the DSM-V criteria plus Autism Diagnostic Observation Schedule (ADOS) criteria for Autism. * Aged 3-8 * Participants must also be enrolled in an early behavioral intervention program at the Thompson Center or another institution in Missouri for the duration of the study.
Exclusion criteria
* Non-autism learning disability (e.g. dyslexia) * Major psychiatric diagnosis (e.g. major depression, schizophrenia, bipolar disorder) * Other neurological diagnosis * Major head trauma * Any of the following exclusionary criteria related to propranolol (diabetes, reactive airway/pulmonary disease, thyroid disease, bradyarrhythmias, unexplained syncope, narrow angle glaucoma, known hypersensitivity/adverse reaction to beta-blockers, potentially interacting drugs, underweight \< 15 kg) * Any of the following exclusionary criteria related to the use of electrocardiogram (history of rash from adhesives) * Any of the following exclusionary criteria related to the pupillary reflex measurement (uncorrectable visual acuity impairment). * Participants with a heart rate of less than 60 or a systolic blood pressure of less than 75 at the outset of the study will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in General Social Outcome Measure (GSOM) | Week 12 | The GSOM is a brief evaluation tool that measures a participant's level of social functioning and how it changes with intervention. There GSOM includes 4 different tasks: conversational reciprocity, ability to recognize facial expressions, social problem solving, affect demonstration, and emotional perspective taking. The experimenter administers each component of the GSOM to the participant and then scores their responses according to a pre-determined scoring rubric. Each component is scored on a 1-5 or 0 - 2 scale, with higher total scores indicating better social functioning. A video camera will be used to record the participant's behavior during GSOM administration for the purposes of having two independent raters score the tasks after the study session is complete. A camera will also be used during the affect demonstration task of the GSOM. The overall score is used. The range is 6-132, with higher scores being better. |
| Change in Social Responsiveness Scale (SRS) | Week 12 | This 65-item, parent-report measure asks questions about a participants' social awareness, social information processing, capacity for reciprocal social responses, social anxiety or avoidance, and characteristic autistic preoccupations or traits. The total score is used with a range of 0-195, with lower scores being better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Vineland Adaptive Behavior Scales-II (VABS) | Week 12 | To assess overall adaptive functioning, the VABS will be administered in the form of a structured interview with the parent/caregiver. The VABS is a well validated assessment used for the full range of our subjects' ages and yields standard scores in Communication, Daily Living Skills, Socialization, and Motor Skills. VABS scores for Socialization will be monitored in this study. The range is 20-160 with higher scores better. |
| Change in Preschool Anxiety Scale (PAS) | Week 12 | To assess anxiety, the PAS will be completed by the parents/caregivers of participants. This self-report measure yields a total score in addition to six subscales (separation anxiety, social phobia, obsessive compulsive, panic/agoraphobia, physical injury fears, and generalized anxiety). The overall score is used. Range is 0-112 with lower score meaning less anxiety. |
| Change in Preschool Language Scale (PLS): | Week 12 | To evaluate language, we will administer the PLS, which has been developed for use in younger children (birth through age 7), and is appropriate for children of all ability levels, including nonverbal children. This play-based, interactive assessment is designed to assess receptive and expressive language skills and their change over time. The range is 50-150 with higher scores being better. |
| Change in Autism Impact Measure (AIM) | Week 12 | The AIM will be administered to assess the frequency and impact of a participant's ASD-related symptoms. A parent/caregiver is asked a series of 41 questions regarding the frequency and the impact, or interference resulting from, a series of autism-associated behaviors. Peer interaction from the AIM is the primary domain obtained from this measure. For this domain the range is 0 to 40, with higher numbers more severe. |
| Change in Aberrant Behavior Checklist (ABC) | Week 12 | To assess overall behavioral disturbances, a parent/caregiver of the participants will complete ABC. This 58-item questionnaire is a well validated, reliable, and widely used assessment tool for interventions for a range of cognitive disorders. The full score is used, with a range of 0-174, with higher scores meaning more behaviors. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Propranolol Group participants assigned to propranolol | 5 |
| Placebo Group participants assigned to placebo | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Worse behavior | 0 | 1 |
Baseline characteristics
| Characteristic | Propranolol Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 4 Participants | 9 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 9 Participants |
| Region of Enrollment United States | 5 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 1 / 5 | 1 / 4 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 |
Outcome results
Primary
Change in General Social Outcome Measure (GSOM)
The GSOM is a brief evaluation tool that measures a participant's level of social functioning and how it changes with intervention. There GSOM includes 4 different tasks: conversational reciprocity, ability to recognize facial expressions, social problem solving, affect demonstration, and emotional perspective taking. The experimenter administers each component of the GSOM to the participant and then scores their responses according to a pre-determined scoring rubric. Each component is scored on a 1-5 or 0 - 2 scale, with higher total scores indicating better social functioning. A video camera will be used to record the participant's behavior during GSOM administration for the purposes of having two independent raters score the tasks after the study session is complete. A camera will also be used during the affect demonstration task of the GSOM. The overall score is used. The range is 6-132, with higher scores being better.
Time frame: Week 12
Population: This is a feasibility study so results are limited.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol Arm | Change in General Social Outcome Measure (GSOM) | 48.3 score on a scale | Standard Deviation 14 |
| Placebo Arm | Change in General Social Outcome Measure (GSOM) | 20.0 score on a scale | Standard Deviation 15.6 |
Primary
Change in Social Responsiveness Scale (SRS)
This 65-item, parent-report measure asks questions about a participants' social awareness, social information processing, capacity for reciprocal social responses, social anxiety or avoidance, and characteristic autistic preoccupations or traits. The total score is used with a range of 0-195, with lower scores being better.
Time frame: Week 12
Population: Feasibility only
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol Arm | Change in Social Responsiveness Scale (SRS) | 79.3 score on a scale | Standard Deviation 17 |
| Placebo Arm | Change in Social Responsiveness Scale (SRS) | 72.0 score on a scale | Standard Deviation 2.8 |
Secondary
Change in Aberrant Behavior Checklist (ABC)
To assess overall behavioral disturbances, a parent/caregiver of the participants will complete ABC. This 58-item questionnaire is a well validated, reliable, and widely used assessment tool for interventions for a range of cognitive disorders. The full score is used, with a range of 0-174, with higher scores meaning more behaviors.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol Arm | Change in Aberrant Behavior Checklist (ABC) | 72.7 score on a scale | Standard Deviation 65.5 |
| Placebo Arm | Change in Aberrant Behavior Checklist (ABC) | 53.0 score on a scale | Standard Deviation 39.6 |
Secondary
Change in Autism Impact Measure (AIM)
The AIM will be administered to assess the frequency and impact of a participant's ASD-related symptoms. A parent/caregiver is asked a series of 41 questions regarding the frequency and the impact, or interference resulting from, a series of autism-associated behaviors. Peer interaction from the AIM is the primary domain obtained from this measure. For this domain the range is 0 to 40, with higher numbers more severe.
Time frame: Week 12
Population: Peer interaction subdomain
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol Arm | Change in Autism Impact Measure (AIM) | 23.7 score on a scale | Standard Deviation 8.7 |
| Placebo Arm | Change in Autism Impact Measure (AIM) | 24.5 score on a scale | Standard Deviation 6.4 |
Secondary
Change in Preschool Anxiety Scale (PAS)
To assess anxiety, the PAS will be completed by the parents/caregivers of participants. This self-report measure yields a total score in addition to six subscales (separation anxiety, social phobia, obsessive compulsive, panic/agoraphobia, physical injury fears, and generalized anxiety). The overall score is used. Range is 0-112 with lower score meaning less anxiety.
Time frame: Week 12
Population: Feasibility only
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol Arm | Change in Preschool Anxiety Scale (PAS) | 87.7 score on a scale | Standard Deviation 32.9 |
| Placebo Arm | Change in Preschool Anxiety Scale (PAS) | 71.5 score on a scale | Standard Deviation 30.4 |
Secondary
Change in Preschool Language Scale (PLS):
To evaluate language, we will administer the PLS, which has been developed for use in younger children (birth through age 7), and is appropriate for children of all ability levels, including nonverbal children. This play-based, interactive assessment is designed to assess receptive and expressive language skills and their change over time. The range is 50-150 with higher scores being better.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol Arm | Change in Preschool Language Scale (PLS): | 87.7 score on a scale | Standard Deviation 32.9 |
| Placebo Arm | Change in Preschool Language Scale (PLS): | 71.5 score on a scale | Standard Deviation 30.4 |
Secondary
Change in Vineland Adaptive Behavior Scales-II (VABS)
To assess overall adaptive functioning, the VABS will be administered in the form of a structured interview with the parent/caregiver. The VABS is a well validated assessment used for the full range of our subjects' ages and yields standard scores in Communication, Daily Living Skills, Socialization, and Motor Skills. VABS scores for Socialization will be monitored in this study. The range is 20-160 with higher scores better.
Time frame: Week 12
Population: Social domain
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol Arm | Change in Vineland Adaptive Behavior Scales-II (VABS) | 70.7 score on a scale | Standard Deviation 10.2 |
| Placebo Arm | Change in Vineland Adaptive Behavior Scales-II (VABS) | 66.5 score on a scale | Standard Deviation 23.3 |