Oxytocin Effects on Bone in Children with Autism Spectrum Disorder

Phase 2

Recruiting

• Conditions: Autism Spectrum Disorder; Bone Health
• Interventions: Drug: 1. Intranasal oxytocin spray; Drug: 2. Intranasal placebo spray; Drug: 3. Intranasal Oxytocin spray

• Registration Number: NCT05754073
• Lead Sponsor: Elizabeth Austen Lawson

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.

Study Timeline

• Study First Submitted: 2023-02-22
• Study First Submitted QC: 2023-02-22
• Study First Posted: 2023-03-03
• Study Start: 2023-08-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-11
• Last Update Posted: 2024-12-16
• Primary Completion: 2025-10-31
• Study Completion: 2026-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

1. Ages 6 to 18 years old at Randomization
2. BMI greater than or equal to the 5th percentile
3. Expert clinical diagnosis of ASD
4. Availability of parent/guardian to provide informed consent

Exclusion Criteria

1. Fragile X, tuberous sclerosis, and other single gene defects that are syndromic
2. Other conditions that may contribute to low bone density (e.g., hypogonadism)
3. Medications that may impact bone other than calcium or vitamin D supplementation
4. Hyponatremia
5. Liver enzymes (AST, ALT, and Bilirubin) more than three times the upper limit of the normal range
6. Estimated glomerular filtration rate (eGFR) less than 60
7. Substance use disorder within the last 6 months
8. History of known coronary artery disease, heart failure, reduced ejection fraction, hypertrophic cardiomyopathy, ventricular arrhythmias, or prolonged QT
9. Active seizures within 6 months preceding the Screening visit or the Baseline visit
10. Subjects who are pregnant, lactating, or who refuse contraception if sexually active
11. Subjects who have had previous treatment with OXT (within 2 months of Randomization)
12. Subjects who are not able to cooperate with medication administration, blood drawing, or imaging procedures despite behavior training
13. Caregivers who are unable to speak English, be consistently present at study visits to report on symptoms or, per the judgement of the data collection team, are unable to comply with the protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1. Intranasal Oxytocin	1. Intranasal oxytocin spray	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
1. Intranasal Oxytocin	3. Intranasal Oxytocin spray	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
2. Placebo	2. Intranasal placebo spray	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
2. Placebo	3. Intranasal Oxytocin spray	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

Primary Outcome Measures

Name	Time	Method
Difference between IN OXT vs placebo in 12-month change in areal BMD Z-score at the femoral neck	12 months

Secondary Outcome Measures

Name	Time	Method
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 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 lean mass and muscle area	12 months

Trial Locations

Locations (2)

University of Virginia Medical Center; 🇺🇸 Charlottesville, Virginia, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States