Oxytocin Effects on Bone Metabolism in Children With Autism Spectrum Disorder

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05754073

Collaborator

United States Department of Defense (U.S. Fed)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder Bone Health	Drug: 1. Intranasal oxytocin spray Drug: 2. Intranasal placebo spray Drug: 3. Intranasal Oxytocin spray	Phase 2

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.

Our study aims 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.

We 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 Design

Study Type:

Interventional

Anticipated Enrollment :

96 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

All subjects and all study staff except the pharmacist will be blinded to treatment assignment.

Primary Purpose:

Prevention

Official Title:

A Randomized, Double-blind, Placebo-controlled Study of Intranasal Oxytocin for Bone Health in Children With Autism Spectrum Disorder

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Oct 31, 2025

Anticipated Study Completion Date :

Oct 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: 1. Intranasal oxytocin spray 30 IU, twice daily for 12 months in the experimental arm in double-blinded phase Drug: 3. Intranasal Oxytocin spray 30 IU, twice daily for 6 months in both experimental and placebo comparator arm in open-label phase
Placebo Comparator: 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	Drug: 2. Intranasal placebo spray 30 IU, twice daily for 12 months in the placebo comparator arm in double-blinded phase Drug: 3. Intranasal Oxytocin spray 30 IU, twice daily for 6 months in both experimental and placebo comparator arm in open-label phase

Arm

Intervention/Treatment

Experimental: 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

Drug: 1. Intranasal oxytocin spray

30 IU, twice daily for 12 months in the experimental arm in double-blinded phase

Drug: 3. Intranasal Oxytocin spray

30 IU, twice daily for 6 months in both experimental and placebo comparator arm in open-label phase

Placebo Comparator: 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

Drug: 2. Intranasal placebo spray

30 IU, twice daily for 12 months in the placebo comparator arm in double-blinded phase

Drug: 3. Intranasal Oxytocin spray

30 IU, twice daily for 6 months in both experimental and placebo comparator arm in open-label phase

Outcome Measures

Primary Outcome Measures

Difference between IN OXT vs placebo in 12-month change in whole body less head areal BMD Z-score [12 months]

Secondary Outcome Measures

Difference between IN OXT vs placebo in 12-month change in femoral neck areal BMD Z-score [12 months]
Difference between IN OXT vs placebo in 12-month change in radial cortical area [12 months]
Difference between IN OXT vs placebo in 12-month change in tibial cortical area [12 months]
Difference between IN OXT vs placebo in 12-month change in radial trabecular thickness [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ages 6 to 18 years old at Randomization
BMI between the 10th-85th percentiles
Expert clinical diagnosis of ASD confirmed using the Diagnostic and Statistical Manual of Mental Disorders (DSM) -5 Checklist and a Social Communication Questionnaire (SCQ)-Lifetime
Availability of parent/guardian to provide informed consent
If cognitively able, the subject must be able to provide informed assent/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., hyperprolactinemia, hypogonadism)
Medications that may impact bone such as specific anti-seizure medications, oral glucocorticoids, combined hormonal contraception
Hyponatremia
Creatinine or liver enzymes more than twice the upper limit of the normal range
Changes in doses of antipsychotics that can cause hyperprolactinemia within 2 months of the baseline visit
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
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
Subjects who have had previous treatment with OXT (within 2 months of Randomization)
Subjects who are not able to cooperate with medication administration, blood drawing, or imaging procedures despite behavior training
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