A Study of Oxytocin in Children and Adolescents With Autistic Disorder (Oxytocin)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Oxytocin in Children and Adolescents With Autistic Disorder|
- Number of Participants Who Could Tolerate Twice Daily Oxytocin [ Time Frame: Week 0 to week 8 ]This study will help to determine tolerability of intranasal oxytocin treatment in children with autism by measuring the ability of at least 80% of the sample to tolerate twice daily intranasal administration of oxytocin.
- Number of Participants Who Could Tolerate Twice Daily Oxytocin [ Time Frame: Week 0 to week 16 ]This study will help to determine tolerability of intranasal oxytocin treatment in children with autism by measuring the ability of at least 80% of the sample to tolerate twice daily intranasal administration of oxytocin.
- Change in Mean Plasma Oxytocin Level During Period 1 - Double Blind Phase [ Time Frame: Week 0 to week 8 ]Blood samples will be collected to obtain proof of concept data regarding changes in afternoon plasma oxytocin levels
- Change in Mean Weight [ Time Frame: between weeks 0 and 8 ]changes during period 1
- Change in Mean Total Social Social Responsiveness Scale (SRS) T-score [ Time Frame: 0-8 weeks, blinded treatment, period 1 ]The 65-item SRS is a standardized measure of the core symptoms of autism. Each item is scored on a 4-point Likert scale. The raw score of each individual item is summed to create a total raw score. The total raw score is then translated into a total T-scores (which are the equivalent of standard scores). Total T-scores results are as follows: 59 and below: within normal limits, 60-65: Mild range of impairment 66-75: Moderate range of impairment 76 or higher: Severe range of impairment.
- Change in Mean Autism Diagnostic Observation Schedule (ADOS) Total Score [ Time Frame: Baseline to 16 Weeks ]The ADOS is a semi-structured assessment used to assess and diagnose individuals suspected of having autism of varying ages, developmental levels, and language skills (from no speech to verbally fluent). The ADOS includes four modules, each requiring just 35-40 minutes to administer. The individual being evaluated is given just one of 4 modules, depending on his or her expressive language level and chronological age. The rater will observe social and communication behaviors during various activities in the appropriate module. A rater then uses a 0-3 scale to rate each type of behavior. A select number of individual items will be summed for a total score representing communication and reciprocal social interaction. In scoring all 3's are collapsed to a 2. A higher score indicates more severe impairment. Ranges of scores are as follows: Module 1: 0-24, Module 2: 0-24, Module 3: 0-22, Module 4: 0-22.
- Change in Mean Aberrant Behavior Checklist (ABC)-Social Withdrawal Subscale Score Over Both Periods [ Time Frame: Baseline to 16 Weeks ]Efficacy measures included the Aberrant Behavior Checklist -Social Withdrawal subscale scor. The ABC which focuses on problem behaviors in five subdomains, including irritability, attention, repetitive behaviors, unusual speech, and lethargy. A modified version of the lethargy subscale was used. Typically the Lethargy subscale includes 16 items, however, for our purposes 3 items that were specifically related to lethargy (i.e.: listlessness) were removed so that the focus could primarily be on aberrant social behavior. Differences in only the Social Withdrawal domain were assessed.The is the sum of items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC- Social Withdrawal total score ranges from 0 to 39. Higher values represent greater severity of illness.
- Change in Mean Pervasive Developmental Disorder Behavior Inventory - Screening Version (PDDBI-SV) Total Score Over Both Periods [ Time Frame: Baseline to 16 Weeks ]The PDDBI-SV examines both adaptive and maladaptive behaviors related to autism. It has normative scores for children between 2-11 years. For children 12 years and older, the norms (11 years, 11 months) will be used. Each item is scored on a scale from 0-3. For the first 9 items, the total of individual items is summed. For items 10-18, the scores are reversed and then summed (i.e.: 0=3, 1 =2, 2=2, 3 = 0). Then the total of 0-9 and then the reversed scored items 10-18 are summed for a final total score. Higher scores indicate more impairment. The range of total scores is 0-54. ASD/Social deficits unlikely: 0-6, More information needed/borderline: 7-10, autism spectrum disorder (ASD)/social deficits likely (mild):11-14, ASD/social deficits likely (moderate): 15-29, ASD/social deficits likely (severe): 30-37, ASD/social deficits likely (extreme): 38 or higher.
- Change in Mean Systolic Blood Pressure During Period 1 [ Time Frame: Week 0 to 8 ]Change in mean systolic blood pressure during double blind phase
- Mean Change in Prolactin Levels Over Period 1 [ Time Frame: Week 0 to 8 ]Serum prolactin levels were collected and analyzed in participants
- Mean Change in Temperature During Period 1 [ Time Frame: Week 0 to 8 ]Temperature was collected on each participant via oral or temporal thermometer. The mean change in each group was assessed.
|Study Start Date:||March 2011|
|Study Completion Date:||April 2013|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Intervention: Drug: placebo
Placebo Nasal Spray
Active Comparator: Oxytocin
Intervention: Drug: Syntocinon® Nasal Spray
Subjects will use the Syntocinon® Nasal Spray (oxytocin) twice daily for 8 weeks if they are randomized to that arm in the Randomized Phase. All subjects will use the Syntocinon® Nasal Spray twice daily for 8 weeks in the Open Label Phase.
Subjects ages 3-10 years old will be titrated up to a maximum dose of 24 International units (IU). Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Other Name: Syntocinon® Nasal Spray
The proposed pilot study is an essential first step toward rigorously evaluating oxytocin treatment of individuals with autism. The biologic actions of oxytocin on social cognition and prosocial behaviors and the clinical, genetic and epigenetic evidence for involvement of the oxytocin system in the pathophysiology of some cases of autism strongly suggest that supplemental oxytocin therapy could significantly improve the social disabilities involved in autism. Many people feel that these social difficulties are the most characteristic and central feature of autism. Overall, this study aims to determine the tolerability, accessibility, and feasibility of an oxytocin pilot study.
This study will consent up to 30 subjects in order to randomize up to 25 subjects into a 2-month (8 weeks) randomized double-blind, placebo-controlled initial treatment period, a subsequent 2-month (8 weeks) period in which all participants receive oxytocin, and up to three post-treatment visits that occur at week 28 (±2 weeks),an interim visit anytime between week 16 and week 76 only for those patients who plan to start oxytocin on their own outside of study treatment and who will experience a lag time between week 16 (end of open label treatment) and when outside oxytocin treatment will begin, and some time before week 76. The investigators hope that this study will help to inform future study designs in determining whether a short term or long term treatment trial is necessary to observe significant effects. This will also help to develop systematic preliminary safety measures.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01308749
|United States, North Carolina|
|University of North Carolina Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|Principal Investigator:||Linmarie Sikich, M.D.||University of North Carolina, Chapel Hill|