A Randomized, Double-blind, Placebo-controlled Study of Intranasal Oxytocin for Bone Health in Children With Autism Spectrum Disorder
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 96
- 试验地点
- 2
- 主要终点
- Difference between IN OXT vs placebo in 12-month change in whole body less head BMD Z-scores.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
盲法说明
All subjects and all study staff except the pharmacist will be blinded to treatment assignment.
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Fragile X, tuberous sclerosis, and other single gene defects that are syndromic
- •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
研究组 & 干预措施
1. Intranasal Oxytocin
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
干预措施: 1. Intranasal oxytocin spray (Drug)
2. Placebo
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
干预措施: 3. Intranasal Oxytocin spray (Drug)
1. Intranasal Oxytocin
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
干预措施: 3. Intranasal Oxytocin spray (Drug)
2. Placebo
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
干预措施: 2. Intranasal placebo spray (Drug)
结局指标
主要结局
Difference between IN OXT vs placebo in 12-month change in whole body less head BMD Z-scores.
时间窗: 12 months
次要结局
- 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 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 lean mass and muscle area(12 months)
研究者
Elizabeth Austen Lawson
Director of the Interdisciplinary Oxytocin Research Program
Massachusetts General Hospital