Oxytocin Effects on Bone in Children With Autism Spectrum Disorder

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Difference between IN OXT vs placebo in 12-month change in whole body less head BMD Z-scores. [Срок оценки: 12 months]

Вторичные конечные точки (5)

• Difference between IN OXT vs placebo in 12-month change in areal BMD Z-score at the femoral neck. [Срок оценки: 12 months]
• Difference between IN OXT vs placebo in 12-month change in radial and tibial cortical area and radial trabecular thickness. [Срок оценки: 12 months]
• Difference between IN OXT vs placebo in 12-month change in radial and tibial failure load. [Срок оценки: 12 months]
• Difference between IN OXT vs placebo in 12-month change in bone turnover markers, cortisol. [Срок оценки: 12 months]
• Difference between IN OXT vs placebo in 12-month change in lean mass and muscle area [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Ages 6 to 18 years old at Randomization
• BMI greater than or equal to the 5th percentile
• Expert clinical diagnosis of ASD
• Availability of parent/guardian to provide informed consent

Критерии исключения

• 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
• Other conditions that may contribute to low bone density (e.g., hypogonadism)
• 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)
• Hyponatremia
• Liver enzymes (AST, ALT, and Bilirubin) more than three times the upper limit of the normal range
• Estimated glomerular filtration rate (eGFR) less than 60
• 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 (QTc greater than or equal to 480 msec)
• 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
• Any significant illness, condition, medication, or medical device that the Investigator determines could interfere with study participation and impact data collection or subject safety

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Профилактика

Центры проведения

США · 2 центра

• Massachusetts General Hospital — Boston
• University of Virginia Medical Center — Charlottesville

Идентификаторы

NCT: NCT05754073 · 2023P000307

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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