Clinical trial NCT05754073: Oxytocin Effects on Bone 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Autism Spectrum Disorder
Bone Health
Keywords: Autism spectrum disorder
Bone density
Oxytocin
Peri-pubertal children
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: University of Virginia
First posted: 2023-03-03
Enrollment: 96
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Difference between IN OXT vs placebo in 12-month change in areal BMD Z-score at the femoral neck
timeFrame: 12 months
Secondary outcomes:
measure: Difference between IN OXT vs placebo in 12-month change in radial and tibial cortical area and radial trabecular thickness.
timeFrame: 12 months
measure: Difference between IN OXT vs placebo in 12-month change in radial and tibial failure load.
timeFrame: 12 months
measure: Difference between IN OXT vs placebo in 12-month change in bone turnover markers, cortisol.
timeFrame: 12 months
measure: Difference between IN OXT vs placebo in 12-month change in lean mass and muscle area
timeFrame: 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
Study officials:
affiliation: Neuroendocrine Unit Massachusetts General Hospital
name: Elizabeth A Lawson, MD
role: PRINCIPAL_INVESTIGATOR
References: