Autism Spectrum Disorders
Conditions
Keywords
Autism, Autism Spectrum Disorders, Oxytocin, Hollander, ASD, Asperger Syndrome, Asperger
Brief summary
Autism Spectrum Disorder (ASD) is a developmental disorder characterized by abnormalities in speech and communication, impaired social functioning and repetitive behaviors and restricted interests. Oxytocin (OT) is peptide that is known for its peripheral effects on facilitating uterine contractions and milk let-down; however, studies, mainly with rodents and non-human primates, has found that OT is involved in affiliative behaviors, including sexual behavior, mother-infant and adult-adult pair-bond formation, separation distress, and other aspects of social attachment. Moreover, OT is known to play an important role in repetitive behaviors and stress reactivity. Given that repetitive behaviors and deficits in social interaction are core symptom domains of autism, and that OT is involved in the regulation of repetitive and affiliative behaviors, it is believed that OT may play a role in the etiology of autism. Moreover, preliminary data obtained by Hollander and colleagues suggests that OT may be of value in treating core autism symptoms. Specifically, synthetic oxytocin administered via intravenous infusion to adults with autism spectrum disorders (ASD) produced significant reductions in repetitive behaviors and facilitated social cognition/memory in a double-blind, placebo-controlled cross-over laboratory challenge. Encouraged by these findings, the primary aim of this study is to investigate the safety and therapeutic efficacy of intranasal OT in treating repetitive behaviors and social functioning/cognitive deficits in adults with ASD. This research embraces a translational approach to develop a novel treatment for core ASD symptoms; given that there are currently no Food and Drug Administration (FDA) approved medication treatments for core ASD symptoms, this research addresses an important unmet need in the field. The goal of this study is to evaluate the safety and efficacy of repeated Intranasal Oxytocin Treatment (INOT)administration in adults with ASD.
Interventions
DRUGIntranasal Oxytocin
Oxytocin administered intranasally twice a day via 1 12 unit puff to each nostril, totaling 48 IU a day.
DRUGPlacebo
Saline will be administered intranasally twice a day via 1 puff per nostril, totaling 48 IU a day.
Sponsors
National Alliance for Research on Schizophrenia and Depression
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Male and Female * 18 to 55 years old * Meet Diagnostic and Statistical Manual-IV (DSM-IV), Autism Diagnostic Observation Schedule(ADOS), and Autism Diagnostic Interview-Revised (ADI-R) standards for Autism Spectrum Disorder or Aspergers Syndrome * Have a high, normal or near normal Intelligent Quotient * Speak and Understand English fluently
Exclusion criteria
* Born prior to 35 weeks gestational age * Any primary psychiatric diagnosis other than autism at the time of screening * Medical history of neurological disease * Medical history of known MRI/structural lesion of the brain * Patients who are pregnant * With a medical condition that might interfere with the conduct of the study, confound interpretation of study results or endanger their own well being * With evidence or history of malignancy or any significant hematological, endocrine, cardiovascular, respiratory, renal, hepatic or gastrointestinal disease * Taking psychoactive medications * Who plan to initiate or change nonpharmacologic interventions during the study course * Who are unable to tolerate venipuncture procedures for blood sampling
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvement on the Clinical Global Impression-Improvement (CGI-I) Scale | 6 Weeks | Rating Scale that utilizes direct observation, scales and patient report to inform clinical judgment. A form of CGI that targets social functioning will be used as the primary outcome measure. Semi-structured interview. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Obsessive- Compulsive Behavior Based on Yale Brown Obsessive Compulsive Scale (YBOCS) | Baseline, Week 6 | Clinician-Rated questionnaire measuring the time spent, distress,interference, resistance, and control in relation to obsessions and compulsions based on a 5 point scale ranging from 0-5 for each category with 0 being most desirable and 5 being least. Sub-scales are added and averaged to obtain total scores. -scale range (total): 0 - 40 total, 0 - 7 subclinical, 8-15 mild, 16 - 23 moderate, 24 - 31 severe, 32 - 40 extreme Questions are rated on a 5-point scale, 0-4, increasing in severity. Obsession Rating Subscale (5 questions, ranging from 0 - 20 total) and Compulsion Rating subscale (5 questions, ranging from 0 - 20 total) are totaled and added to obtain total scores. -score interpretation: Higher overall scores reflect increasing symptom severity. |
| Change in Repetitive Behavior Based Repetitive Behavior Scale - Revised (RBS-R) | Baseline, week 6 | Subscale ranges: stereotypic behavior (0 - 27);self-injurious behavior (0 - 24); compulsive behavior (0 - 18); ritualistic/Sameness Behavior (0 - 36); restricted Interests (0 - 9). Higher score in all subscales reflect increasing severity. Questions rate behaviors on a 4-point scale: 0 = does not occur; 1 = occurs, mild problem; 2 = occurs, moderate problem; 3 = occurs, severe problem. Subscale scores consist of sum of ratings within each question subset. Lower order behaviors-- stereotypy and self-injury, higher order behaviors--compulsions, rituals /sameness, restricted interests. Lower Order total range: 0-51, Higher Order total range: 0-63 Stereotypic behavior and Self-injurious behavior subscales were summed to create a total range for Lower Order behavior; and Compulsive behavior, ritualistic /sameness behavior, and restricted interests subscales were summed to create a total range for Higher Order behavior. |
| Change in Facial Emotion Recognition Based on Diagnostic Analysis of Nonverbal Accuracy - 2 (DANVA-2) | baseline, week 6 | A clinical tool measuring emotion recognition through facial expression, voice and posture. 1. Child faces 2 (range 0 - 100, higher values reflecting higher % of errors) 2. Adult faces 2 (range 0 - 100, higher values reflecting higher % of errors) 3. Child paralanguage 2 (range 0 - 100, higher values reflecting higher % of errors) 4. Adult paralanguage 2 (range 0 - 100, higher values reflecting higher % of errors) Errors are counted and organized by pre-determined affect and intensity. Subtests considered separately. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin Intranasal Oxytocin: Oxytocin administered intranasally twice a day via 1 12 unit puff to each nostril, totaling 48 IU a day. | 10 |
| Placebo Placebo: Saline will be administered intranasally twice a day via 1 puff per nostril, totaling 48 IU a day. | 9 |
| Total | 19 |
Baseline characteristics
| Characteristic | Placebo | Oxytocin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 10 Participants | 19 Participants |
| Age, Continuous | 32.9 years | 33.8 years | 33.2 years |
| Region of Enrollment United States | 9 participants | 10 participants | 1 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 10 | 0 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 |
Outcome results
Primary
Number of Participants With Improvement on the Clinical Global Impression-Improvement (CGI-I) Scale
Rating Scale that utilizes direct observation, scales and patient report to inform clinical judgment. A form of CGI that targets social functioning will be used as the primary outcome measure. Semi-structured interview.
Time frame: 6 Weeks
Population: Participants rated as improved on the CGI-I scale
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oxytocin | Number of Participants With Improvement on the Clinical Global Impression-Improvement (CGI-I) Scale | 3 Participants |
| Placebo | Number of Participants With Improvement on the Clinical Global Impression-Improvement (CGI-I) Scale | 1 Participants |
Secondary
Change in Facial Emotion Recognition Based on Diagnostic Analysis of Nonverbal Accuracy - 2 (DANVA-2)
A clinical tool measuring emotion recognition through facial expression, voice and posture. 1. Child faces 2 (range 0 - 100, higher values reflecting higher % of errors) 2. Adult faces 2 (range 0 - 100, higher values reflecting higher % of errors) 3. Child paralanguage 2 (range 0 - 100, higher values reflecting higher % of errors) 4. Adult paralanguage 2 (range 0 - 100, higher values reflecting higher % of errors) Errors are counted and organized by pre-determined affect and intensity. Subtests considered separately.
Time frame: baseline, week 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Change in Facial Emotion Recognition Based on Diagnostic Analysis of Nonverbal Accuracy - 2 (DANVA-2) | DANVA -Face Baseline | 32.6 units on a scale | Standard Deviation 8.8 |
| Oxytocin | Change in Facial Emotion Recognition Based on Diagnostic Analysis of Nonverbal Accuracy - 2 (DANVA-2) | DANVA- FACE Week 6 | 33.5 units on a scale | Standard Deviation 6.4 |
| Oxytocin | Change in Facial Emotion Recognition Based on Diagnostic Analysis of Nonverbal Accuracy - 2 (DANVA-2) | DANVA- Paralanguage Baseline | 27.8 units on a scale | Standard Deviation 5.7 |
| Oxytocin | Change in Facial Emotion Recognition Based on Diagnostic Analysis of Nonverbal Accuracy - 2 (DANVA-2) | DANVA- Paralanguage Week 6 | 30.5 units on a scale | Standard Deviation 2.7 |
| Placebo | Change in Facial Emotion Recognition Based on Diagnostic Analysis of Nonverbal Accuracy - 2 (DANVA-2) | DANVA- Paralanguage Week 6 | 35.2 units on a scale | Standard Deviation 4.7 |
| Placebo | Change in Facial Emotion Recognition Based on Diagnostic Analysis of Nonverbal Accuracy - 2 (DANVA-2) | DANVA -Face Baseline | 39.1 units on a scale | Standard Deviation 8.4 |
| Placebo | Change in Facial Emotion Recognition Based on Diagnostic Analysis of Nonverbal Accuracy - 2 (DANVA-2) | DANVA- Paralanguage Baseline | 34.1 units on a scale | Standard Deviation 3 |
| Placebo | Change in Facial Emotion Recognition Based on Diagnostic Analysis of Nonverbal Accuracy - 2 (DANVA-2) | DANVA- FACE Week 6 | 37.4 units on a scale | Standard Deviation 7.4 |
Secondary
Change in Obsessive- Compulsive Behavior Based on Yale Brown Obsessive Compulsive Scale (YBOCS)
Clinician-Rated questionnaire measuring the time spent, distress,interference, resistance, and control in relation to obsessions and compulsions based on a 5 point scale ranging from 0-5 for each category with 0 being most desirable and 5 being least. Sub-scales are added and averaged to obtain total scores. -scale range (total): 0 - 40 total, 0 - 7 subclinical, 8-15 mild, 16 - 23 moderate, 24 - 31 severe, 32 - 40 extreme Questions are rated on a 5-point scale, 0-4, increasing in severity. Obsession Rating Subscale (5 questions, ranging from 0 - 20 total) and Compulsion Rating subscale (5 questions, ranging from 0 - 20 total) are totaled and added to obtain total scores. -score interpretation: Higher overall scores reflect increasing symptom severity.
Time frame: Baseline, Week 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Change in Obsessive- Compulsive Behavior Based on Yale Brown Obsessive Compulsive Scale (YBOCS) | Baseline | 12.0 score on a scale | Standard Deviation 3.9 |
| Oxytocin | Change in Obsessive- Compulsive Behavior Based on Yale Brown Obsessive Compulsive Scale (YBOCS) | Week 6 | 9.4 score on a scale | Standard Deviation 2.9 |
| Placebo | Change in Obsessive- Compulsive Behavior Based on Yale Brown Obsessive Compulsive Scale (YBOCS) | Baseline | 10.3 score on a scale | Standard Deviation 2.5 |
| Placebo | Change in Obsessive- Compulsive Behavior Based on Yale Brown Obsessive Compulsive Scale (YBOCS) | Week 6 | 8.1 score on a scale | Standard Deviation 2.5 |
Secondary
Change in Repetitive Behavior Based Repetitive Behavior Scale - Revised (RBS-R)
Subscale ranges: stereotypic behavior (0 - 27);self-injurious behavior (0 - 24); compulsive behavior (0 - 18); ritualistic/Sameness Behavior (0 - 36); restricted Interests (0 - 9). Higher score in all subscales reflect increasing severity. Questions rate behaviors on a 4-point scale: 0 = does not occur; 1 = occurs, mild problem; 2 = occurs, moderate problem; 3 = occurs, severe problem. Subscale scores consist of sum of ratings within each question subset. Lower order behaviors-- stereotypy and self-injury, higher order behaviors--compulsions, rituals /sameness, restricted interests. Lower Order total range: 0-51, Higher Order total range: 0-63 Stereotypic behavior and Self-injurious behavior subscales were summed to create a total range for Lower Order behavior; and Compulsive behavior, ritualistic /sameness behavior, and restricted interests subscales were summed to create a total range for Higher Order behavior.
Time frame: Baseline, week 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Change in Repetitive Behavior Based Repetitive Behavior Scale - Revised (RBS-R) | Baseline: Higher Order | 17.0 score on a scale | Standard Deviation 10.6 |
| Oxytocin | Change in Repetitive Behavior Based Repetitive Behavior Scale - Revised (RBS-R) | Week 6:Higher Order | 17.7 score on a scale | Standard Deviation 16.2 |
| Oxytocin | Change in Repetitive Behavior Based Repetitive Behavior Scale - Revised (RBS-R) | Baseline: Lower Order | 5.8 score on a scale | Standard Deviation 4.6 |
| Oxytocin | Change in Repetitive Behavior Based Repetitive Behavior Scale - Revised (RBS-R) | Week 6: Lower Order | 2.4 score on a scale | Standard Deviation 2.3 |
| Placebo | Change in Repetitive Behavior Based Repetitive Behavior Scale - Revised (RBS-R) | Week 6: Lower Order | 3.7 score on a scale | Standard Deviation 2.6 |
| Placebo | Change in Repetitive Behavior Based Repetitive Behavior Scale - Revised (RBS-R) | Baseline: Higher Order | 20.0 score on a scale | Standard Deviation 10.8 |
| Placebo | Change in Repetitive Behavior Based Repetitive Behavior Scale - Revised (RBS-R) | Baseline: Lower Order | 4.9 score on a scale | Standard Deviation 3.7 |
| Placebo | Change in Repetitive Behavior Based Repetitive Behavior Scale - Revised (RBS-R) | Week 6:Higher Order | 17.8 score on a scale | Standard Deviation 13.3 |