Phase 2 Study: Intranasal Oxytocin vs. Placebo for the Treatment of Hyperphagia in Children and Adolescents With Prader-Willi Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Change in Efficacy of Peptide Intranasal Oxytocin (IN-OXT)
研究概览
简要总结
This study is a phase 2 randomized double blind 8-week treatment trial of intranasal OXT vs. placebo in 50 subjects aged 5 to 17 years with PWS in order to assess IN-OXT's affect on measurements of (1) eating behaviors (2) repetitive behaviors (3) weight and body composition (4) quality of life (5) salivary OXT and hormone levels (including ghrelin, pancreatic polypeptide, peptide YY, Glucagon-Like Peptide-1 (GLP-1), insulin, glucagon, testosterone, and estrogen). If superior to placebo, this data will add to the current knowledge that OXT is an effective treatment for hyperphagia as well as other symptoms of PWS.
Funding Source- FDA OOPD
详细描述
Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder caused by lack of expression of paternally derived imprinted material on chromosome 15q11-q13. PWS is characterized by mild to moderate intellectual disabilities, repetitive/compulsive behaviors and rigidity, social cognition deficits and severe hypotonia at birth, followed by the onset of hyperphagia later in life. Obesity is responsible for the majority of the morbidity and mortality associated with PWS, and compulsive eating behaviors are most responsible for diminishing the quality of life for caregivers and family members. Oxytocin has been implicated in the pathophysiology of PWS and there have been small studies of intranasal oxytocin (IN-OXT) in this population. To date, however, studies have not been adequately powered to detect significance in target symptoms of hyperphagia and associated symptoms of individuals with PWS. The primary goal of this study is to examine the safety and efficacy of IN-OXT on hyperphagia, as measured by the Hyperphagia Questionnaire-Clinical Trails, from baseline to week 8. Currently, there are no effective treatments available to manage hyperphagia in patients with PWS.
STUDY DESIGN: This is an 8-week double-blind, randomized study in 50 children with PWS aged 5-17. Participation involves 2 in-person visits to our program and 5 remote visits. Travel expenses will be reimbursed to participating families.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female pediatric outpatients aged 5 to 17 years
- •Must be in PWS nutritional phase 2b or 3 as determined by PI
- •Must be on growth hormone treatment and have been receiving stable doses of growth hormone treatment for at least 3 months prior to screening date. Treatment cannot have been interrupted for more than one week within 3 months of screening.
- •Diagnosis of PWS confirmed by patient medical records.
- •A score of at least moderate severity on the Hyperphagia Questionnaire for Clinical Trials at both screening and baseline visits.
- •Stable dosages of hormone treatments (including testosterone and estrogen supplements) for 4 weeks prior to randomization and for the duration of the study.
- •Stable dosages of metabolic treatments that could affect appetite (including metformin) for 4 weeks prior to randomization and for the duration of the study.
- •Physical exam and laboratory results that are within the normal range for individuals with PWS.
- •Presence of a parent/caregiver/guardian that is able to consent for their participation and complete assessments regarding the child's development and behavior change throughout the study.
排除标准
- •Exposure to any investigational agent in the 30 days prior to randomization.
- •Child not receiving growth hormone treatment
- •Children weighing less than 40 lbs
- •Children with unstable Type 2 Diabetes confirmed by Hemoglobin A1C levels at screening
- •Children with unstable medical co-morbidities at baseline.
- •Children with active upper respiratory infections at screening.
- •A primary psychiatric diagnosis other than Autism Spectrum Disorder (ASD), including bipolar disorder, psychosis, schizophrenia, Post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). These patients will be excluded due to potential confounding results.
- •Pregnant or lactating patients or patients who will not agree to use a double barrier method of contraception. IN-OXT has not been studied in pregnant or lactating women.
- •Females using an estrogen-based contraceptive. As an alternative to an estrogen based contraceptive, subjects will be counseled to use progesterone-based contraceptives; cervical cap; cervical sponges; or spermicidal foam in combination with a condom. Subjects will need to use a double barrier method to be in the study.
- •A medical condition that might interfere with the conduct of the study, confound interpretation of study results or endanger the subject's well-being.
- •A known diagnosis of Rett's Syndrome of Childhood Disintegrative Disorder or marked sensory impairment such as deafness or blindness.
- •Subjects who have changes in allied health therapies, behavioral or educational interventions within four weeks prior to randomization other than those associated with school holidays.
- •Subjects who have had changes in medications or medication doses of risperidone, aripiprazole, other antipsychotic medications, clonidine, guanfacine, stimulants or anti-convulsants within four weeks of randomization.
研究组 & 干预措施
Experimental: Intranasal Oxytocin (IN-OXT)
Syntocinon (synthetic oxytocin) will be used in this protocol. Each subject will receive a dose of 16 IU QD ("quaque die" or once a day) and will be instructed to inhale 2 puffs per nostril (4 IU each).
干预措施: Intranasal Oxytocin (IN-OXT) (Drug)
Placebo Comparator: Matched Placebo
Each subject will receive a dose of 16 IU QD, and will be instructed to inhale 2 puffs per nostril (4 IU each).
干预措施: Matched Placebo (Drug)
结局指标
主要结局
Change in Efficacy of Peptide Intranasal Oxytocin (IN-OXT)
时间窗: From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)
Change in efficacy of peptide IN-OXT as measured by changes in hyperphagia from baseline will be assessed using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). HQ-CT is a caregiver-rated assessment comprised of 9-items that measures the frequency and intensity of hyperphagic behaviors, over the preceding two weeks, in participants with Prader-Willi Syndrome (PWS). The HQ-CT total score is created by summing the 9 item-level responses (ranging from 0 to 4) for a possible range of 0-36 with higher scores indicate more extreme hyperphagia. For purposes of this outcome measure, negative scores represent a decrease in hyperphagia from baseline and positive scores represent an increase in hyperphagia from baseline.
次要结局
- Change in Repetitive Behavior(From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks))
- Change in Rigid Behavior(From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks))
- Change in Body Weight(From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks))
- Body Composition(8 weeks)
- Change in Body Mass Index (BMI)(From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks))
- Change in Quality of Life (QOL) and Caregiver Burden as Determined by the World Health Organization Quality of Life (WHOQOL-BREF) Questionnaire: Domain 1 (Physical Health)(From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks))
- Change in Quality of Life (QOL) and Caregiver Burden as Determined by the World Health Organization Quality of Life (WHOQOL-BREF) Questionnaire - Domain 2 (Psychological Health)(From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks))
- Change in Quality of Life (QOL) and Caregiver Burden as Determined by the World Health Organization Quality of Life (WHOQOL-BREF) Questionnaire - Domain 3 (Social Relationships)(From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks))
- Change in Quality of Life (QOL) and Caregiver Burden as Determined by the World Health Organization Quality of Life (WHOQOL-BREF) Questionnaire - Domain 4 (Environment)(From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks))
- Change in Caregiver Strain(From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks))
- Change in Aberrant Behavior(From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks))
- Change in Salivary Oxytocin Concentration(From Baseline until collections at 1 hour (Day 1), Week 4 and Week 8)
- Clinical Global Impression Scale - Improvement (CGI-I)(8 weeks (measuring change over 8 weeks))
研究者
Eric Hollander
Director, Autism and Obsessive Compulsive Spectrum Program and Professor, Department of Psychiatry and Behavioral Sciences
Montefiore Medical Center