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Oxytocin Effects on Bone Metabolism in Children With Autism Spectrum Disorder

Primary Purpose

Autism Spectrum Disorder, Bone Health

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
1. Intranasal oxytocin spray
2. Intranasal placebo spray
3. Intranasal Oxytocin spray
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Autism Spectrum Disorder focused on measuring Autism spectrum disorder, Bone density, Oxytocin, Peri-pubertal children

Eligibility Criteria

6 Years - 18 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

  • Massachusetts General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1. Intranasal Oxytocin

2. Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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.
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.
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.

Full Information

First Posted
February 22, 2023
Last Updated
October 17, 2023
Sponsor
Massachusetts General Hospital
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT05754073
Brief Title
Oxytocin Effects on Bone Metabolism in Children With Autism Spectrum Disorder
Official Title
A Randomized, Double-blind, Placebo-controlled Study of Intranasal Oxytocin for Bone Health in Children With Autism Spectrum Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2023 (Actual)
Primary Completion Date
October 31, 2025 (Anticipated)
Study Completion Date
October 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
United States Department of Defense

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism Spectrum Disorder, Bone Health
Keywords
Autism spectrum disorder, Bone density, Oxytocin, Peri-pubertal children

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
All subjects and all study staff except the pharmacist will be blinded to treatment assignment.
Allocation
Randomized
Enrollment
96 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1. Intranasal Oxytocin
Arm Type
Experimental
Arm Description
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
Arm Title
2. Placebo
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
1. Intranasal oxytocin spray
Intervention Description
30 IU, twice daily for 12 months in the experimental arm in double-blinded phase
Intervention Type
Drug
Intervention Name(s)
2. Intranasal placebo spray
Intervention Description
30 IU, twice daily for 12 months in the placebo comparator arm in double-blinded phase
Intervention Type
Drug
Intervention Name(s)
3. Intranasal Oxytocin spray
Intervention Description
30 IU, twice daily for 6 months in both experimental and placebo comparator arm in open-label phase
Primary Outcome Measure Information:
Title
The 12-month change in the whole body less head areal BMD Z-score between IN OXT vs. placebo
Description
A whole body less head areal BMD Z-score between -2 to +2 indicates normal bone mineral density
Time Frame
12 months
Secondary Outcome Measure Information:
Title
The 12-month change in femoral neck areal BMD Z-score between IN OXT vs. placebo
Description
A femoral neck areal BMD Z-score between -2 to +2 indicates normal bone mineral density
Time Frame
12 months
Title
The 12-month change in the radial cortical area between IN OXT vs. placebo
Description
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.
Time Frame
12 months
Title
The 12-month change in tibial cortical area between IN OXT vs. placebo
Description
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.
Time Frame
12 months
Title
The 12-month change in radial trabecular thickness between IN OXT vs. placebo
Description
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.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Madhusmita Misra, MD, MPH
Phone
617-726-5790
Email
mmisra@mgh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Smith, DNP
Phone
617-726-9394
Email
ssmith133@mgh.harvard.edu
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Smith, DNP
Phone
617-726-9394
Email
ssmith133@mgh.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Oxytocin Effects on Bone Metabolism in Children With Autism Spectrum Disorder

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