Oxytocin Effects on Bone Metabolism in Children With Autism Spectrum Disorder

Autism Spectrum Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05754073
• Other study ID #: 2023P000307
• Status: Recruiting
• Phase: Phase 2
• Start date: August 1, 2023
• Est. completion date: October 31, 2026

Study information

• Verified date: October 2023
• Source: Massachusetts General Hospital
• Contact: Madhusmita Misra, MD, MPH
• Phone: 617-726-5790
• Email: mmisra[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: October 31, 2026
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Ages 6 to 18 years old at Randomization

2. BMI between the 10th-85th percentiles

3. 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

4. Availability of parent/guardian to provide informed consent

5. If cognitively able, the subject must be able to provide informed assent/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., hyperprolactinemia, hypogonadism)

3. Medications that may impact bone such as specific anti-seizure medications, oral glucocorticoids, combined hormonal contraception

4. Hyponatremia

5. Creatinine or liver enzymes more than twice the upper limit of the normal range

6. Changes in doses of antipsychotics that can cause hyperprolactinemia within 2 months of the baseline visit

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

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Bone Health
• Child Development Disorders, Pervasive

Intervention

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

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The 12-month change in the whole body less head areal BMD Z-score between IN OXT vs. placebo	A whole body less head areal BMD Z-score between -2 to +2 indicates normal bone mineral density	12 months
Secondary	The 12-month change in femoral neck areal BMD Z-score between IN OXT vs. placebo	A femoral neck areal BMD Z-score between -2 to +2 indicates normal bone mineral density	12 months
Secondary	The 12-month change in the radial cortical area between IN OXT vs. placebo	High-resolution peripheral quantitative computed topography (HR-pQCT) will be used to assess the radial cortical area at the non-dominant wrist (if fracture history, then non-fractured side will be used). Using a scout, the reference line will be set at the bone endplate. Scans will be acquired at a distance from the endplate relative to the individual's limb length (ultradistal sites: 7%; diaphyseal sites: 30%) to adjust for body size. Each scan includes 168 slices with an isotropic voxel size of 61 µm3.	12 months
Secondary	The 12-month change in tibial cortical area between IN OXT vs. placebo	High-resolution peripheral quantitative computed topography (HR-pQCT) will be used to assess the tibial cortical area at the non-dominant leg (if fracture history, then non-fractured side will be used). Using a scout, the reference line will be set at the bone endplate. Scans will be acquired at a distance from the endplate relative to the individual's limb length (ultradistal sites: 7%; diaphyseal sites: 30%) to adjust for body size. Each scan includes 168 slices with an isotropic voxel size of 61 µm3.	12 months
Secondary	The 12-month change in radial trabecular thickness between IN OXT vs. placebo	High-resolution peripheral quantitative computed topography (HR-pQCT) will be used to assess the radial trabecular thickness at the non-dominant wrist (if fracture history, then non-fractured side will be used). Using a scout, the reference line will be set at the bone endplate. Scans will be acquired at a distance from the endplate relative to the individual's limb length (ultradistal sites: 7%; diaphyseal sites: 30%) to adjust for body size. Each scan includes 168 slices with an isotropic voxel size of 61 µm3. The trabecular thickness will be calculated using the direct 3D distance transformation method.	12 months