Autism Spectrum Disorder, Bone Health
Conditions
Keywords
Autism spectrum disorder, Bone density, Oxytocin, Peri-pubertal children
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.
Interventions
DRUG1. Intranasal oxytocin spray
30 IU, twice daily for 12 months in the experimental arm in double-blinded phase
DRUG2. Intranasal placebo spray
30 IU, twice daily for 12 months in the placebo comparator arm in double-blinded phase
DRUG3. Intranasal Oxytocin spray
30 IU, twice daily for 6 months in both experimental and placebo comparator arm in open-label phase
Sponsors
Elizabeth Austen Lawson
United States Department of Defense
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
All subjects and all study staff except the pharmacist will be blinded to treatment assignment.
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
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, William's syndrome, Angelman's syndrome, Noonan syndrome, and other single gene defects that are syndromic and affect heart or bone density 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, other than calcium or vitamin D supplementation, such as specific anti-seizure medications (Phenytoin, Phenobarbital), oral glucocorticoids, hormonal contraceptive injection (Medroxyprogesterone acetate (Depo-Provera) 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 (QTc greater than or equal to 480 msec) 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 14. Any significant illness, condition, medication, or medical device that the Investigator determines could interfere with study participation and impact data collection or subject safety
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Difference between IN OXT vs placebo in 12-month change in whole body less head BMD Z-scores. | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Difference between IN OXT vs placebo in 12-month change in areal BMD Z-score at the femoral neck. | 12 months |
| 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 |
Countries
United States
Contacts
CONTACTMadhusmita Misra, MD, MPH
CONTACTSarah Smith, DNP
PRINCIPAL_INVESTIGATORElizabeth A Lawson, MD
Neuroendocrine Unit Massachusetts General Hospital
Outcome results
None listed