A Randomized, Double-blind, Placebo-controlled Study of Intranasal Oxytocin for Bone Health in Children With Autism Spectrum Disorder
Overview
- Phase
- Phase 2
- Intervention
- 1. Intranasal oxytocin spray
- Conditions
- Autism Spectrum Disorder
- Sponsor
- Elizabeth Austen Lawson
- Enrollment
- 96
- Locations
- 2
- Primary Endpoint
- Difference between IN OXT vs placebo in 12-month change in whole body less head BMD Z-scores.
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
This is a randomized, double blind, placebo-controlled study of the effects of intranasal oxytocin on bone health in children with autism spectrum disorder, ages 6-18 years old. Subjects will be randomized to receive intranasal oxytocin or placebo (30 IU, 2 times daily) for 12 months in the double-blind phase, followed by a 6-month open label phase during which all study subjects will receive intranasal oxytocin (30 IU, 2 times daily). Study visits include screening to determine eligibility, followed by study visits at baseline, week 2, and months 6, 12, 18 and phone calls every two weeks for the first two months and monthly thereafter for the duration of the study. Study assessments include history and physical examinations, anthropometric measurements, electrocardiogram (EKG), adverse event monitoring, laboratory tests for chemistries, hormones and biomarkers for bone metabolism, questionnaires regarding diet and exercise, and imaging to assess body composition, bone density and structure.
Detailed Description
The prevalence of autism spectrum disorder (ASD), a group of behaviorally-defined disorders characterized by impaired social interactions and verbal and non-verbal communication, is increasing among children. Studies have shown that children with ASD are at a higher risk for low bone mineral density and fractures. ASD is also characterized by low levels of oxytocin (OXT), a peptide hormone with prosocial effects. In addition, OXT promotes bone formation over resorption and low levels of OXT are associated with poor bone health. Hence, OXT administration represents a potential strategy for improving bone health in children with ASD, particularly during the childhood and adolescent years when bone accrual peaks. The investigators aim to examine (i) whether intranasal OXT administration vs. placebo increases areal bone mineral density (BMD) and improves overall bone health in children with ASD, and (ii) other pathways whereby OXT may impact bone health favorably. The investigators will enroll 96 participants 6-18 years old with ASD and randomize them into the intranasal oxytocin vs. placebo groups. The study subjects will undergo history and physical examinations, anthropometric measurements, electrocardiogram (EKG), adverse event monitoring, laboratory tests for chemistries, hormones and biomarkers for bone metabolism, questionnaires regarding diet and exercise, and imaging to assess body composition, bone density and structure.
Investigators
Elizabeth Austen Lawson
Director of the Interdisciplinary Oxytocin Research Program
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Ages 6 to 18 years old at Randomization
- •BMI greater than or equal to the 5th percentile
- •Expert clinical diagnosis of ASD
- •Availability of parent/guardian to provide informed consent
Exclusion Criteria
- •Fragile X, tuberous sclerosis, and other single gene defects that are syndromic
- •Other conditions that may contribute to low bone density (e.g., hypogonadism)
- •Medications that may impact bone other than calcium or vitamin D supplementation, other than calcium or vitamin D supplementation, such as specific anti-seizure medications (Phenytoin, Phenobarbital), oral glucocorticoids, hormonal contraceptive injection (Medroxyprogesterone acetate (Depo-Provera)
- •Hyponatremia
- •Liver enzymes (AST, ALT, and Bilirubin) more than three times the upper limit of the normal range
- •Estimated glomerular filtration rate (eGFR) less than 60
- •Substance use disorder within the last 6 months
- •History of known coronary artery disease, heart failure, reduced ejection fraction, hypertrophic cardiomyopathy, ventricular arrhythmias, or prolonged QT (QTc greater than or equal to 480 msec)
- •Active seizures within 6 months preceding the Screening visit or the Baseline visit
- •Subjects who are pregnant, lactating, or who refuse contraception if sexually active
Arms & Interventions
1. Intranasal Oxytocin
Intranasal oxytocin spray (30 IU twice daily) for 12 months in the double-blinded phase followed by intranasal oxytocin spray (30 IU twice daily) for 6-months in the open-label phase
Intervention: 1. Intranasal oxytocin spray
2. Placebo
Intranasal placebo spray (30 IU twice daily (total 60 IU per day) for 12 months followed by intranasal oxytocin spray (30 IU twice daily) for 6-months in the open-label phase
Intervention: 3. Intranasal Oxytocin spray
1. Intranasal Oxytocin
Intranasal oxytocin spray (30 IU twice daily) for 12 months in the double-blinded phase followed by intranasal oxytocin spray (30 IU twice daily) for 6-months in the open-label phase
Intervention: 3. Intranasal Oxytocin spray
2. Placebo
Intranasal placebo spray (30 IU twice daily (total 60 IU per day) for 12 months followed by intranasal oxytocin spray (30 IU twice daily) for 6-months in the open-label phase
Intervention: 2. Intranasal placebo spray
Outcomes
Primary Outcomes
Difference between IN OXT vs placebo in 12-month change in whole body less head BMD Z-scores.
Time Frame: 12 months
Secondary Outcomes
- Difference between IN OXT vs placebo in 12-month change in radial and tibial failure load.(12 months)
- Difference between IN OXT vs placebo in 12-month change in bone turnover markers, cortisol.(12 months)
- Difference between IN OXT vs placebo in 12-month change in areal BMD Z-score at the femoral neck.(12 months)
- Difference between IN OXT vs placebo in 12-month change in radial and tibial cortical area and radial trabecular thickness.(12 months)
- Difference between IN OXT vs placebo in 12-month change in lean mass and muscle area(12 months)