An Open Label Trial of Growth Hormone in Children and Adolescents With Phelan-McDermid Syndrome Targeting Social Withdrawal
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- ABC - Social Withdrawal Subscale
研究概览
简要总结
Phelan McDermid syndrome (PMS) is a rare genetic form of autism spectrum disorder (ASD) due to deletions or mutations in the SHANK3 gene. This is a pilot open labeled trial of growth hormone therapy in children with PMS targeting social withdrawal and repetitive behavior. This research study will include children with PMS between 2-12 years of age who will receive growth hormone daily for 12 weeks, if found to be eligible. The aim of this study is to evaluate the effect of growth hormone on behavioral outcomes such as the aberrant behavior checklist social withdrawal subscale (ABC-SW) and repetitive behavior scale- revised (RBS-R). The effects of growth hormone on visual evoked potentials will also be assessed. Growth hormone increases insulin like growth factor 1 (IGF-1) levels and a previous trial of IGF-1 therapy in PMS children showed improvement in these behavioral scales. Growth hormone has been studied for decades with an excellent safety profile and fewer adverse effects compared to IGF-1 therapy in other conditions. Hence, this may be a viable therapeutic option. There is no treatment currently available for PMS and this trial is therefore extremely important.
详细描述
BACKGROUND: Phelan-McDermid syndrome (PMS) is a genetic form of autism spectrum disorder (ASD) associated with developmental delay and hypotonia. IGF-1 promotes brain vessel growth, neurogenesis, and synaptogenesis.
The research team previous clinical trial of IGF-1 in patients with Phelan McDermid Syndrome has shown improvement in core ASD symptoms using the Aberrant Behavior Checklist (ABC) and the Repetitive Behavior Scale-Revised (RBS-R). Growth hormone (GH) binds to its receptor and initiates a cascade of events which directly increases synthesis and release of IGF-1 levels. HYPOTHESIS: The study team hypothesize that rise in IGF-1 stimulated by growth hormone (GH) administration should produce improvement in behavior in children and adolescents with PMS as previously demonstrated with use of IGF-1.
RESEARCH PLAN: The study team seek to recruit 10 patients with PMS and administer growth hormone as once daily subcutaneous injections for 12 weeks at standard doses. The study team will monitor baseline anthropometric measures, laboratory parameters for growth, IGF-1 levels, and bone age prior to therapy and continue to monitor safety laboratory parameters during and after therapy. The goal of therapy would be to maintain IGF-1 levels between 1-2SD above the mean for age and puberty. Evaluations will include validated behavioral scales. Visual evoked potentials (VEPs) will be used as biomarkers of visual sensory reactivity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Known pathogenic deletions or mutations in SHANK3 gene diagnosed by array CGH and/or direct sequencing.
- •Children between 2 and 12 years of age.
- •Open epiphyses on bone age x ray
排除标准
- •closed epiphyses;
- •active or suspected neoplasia;
- •intracranial hypertension;
- •hepatic insufficiency;
- •renal insufficiency;
- •cardiomegaly/valvulopathy;
- •history of allergy to growth hormone or any component of the formulation (mecasermin);
- •history of extreme prematurity (<1000 grams) with associated early neo-natal complications, e.g. intra-cerebral
- •hemorrhage, prolonged hypoxia, prolonged hypoglycemia;
- •patients with comorbid conditions who are deemed too medically compromised to tolerate the risk of experimental treatment with growth hormone.
- •Patient with visual problems that preclude the use of VEP's
研究组 & 干预措施
Phelan-McDermid syndrome
Patients with Phelan-McDermid syndrome receive 12 weeks of growth hormone therapy
干预措施: Recombinant human Growth hormone (Drug)
结局指标
主要结局
ABC - Social Withdrawal Subscale
时间窗: After 12 weeks of growth hormone therapy
A caregiver report symptom checklist. 58-item instrument into 5 subscales: Irritability (score 0-45); Lethargy/Social Withdrawal (score 0-48); Stereotypic Behavior (score 0-21); Hyperactivity (score 0-48); Inappropriate Speech (score 0-12). Total scale 0-174, with higher score indicating more aberrant behavior.
Repetitive Behavior Scale-Revised (RBS-R)
时间窗: After 12 weeks of growth hormone therapy
A 43 item instrument with total score from 0-129, with higher score indicating more restricted, repetitive and stereotyped behaviors. Subscales Stereotyped Behavior (0-27) Self-injurious Behavior (0-24) Compulsive Behavior (0-18) Ritualistic Behavior (0-36) Sameness Behavior (0-33) Restricted Behavior (0-12)
The Sensory Profile
时间窗: After 12 weeks of growth hormone therapy
The full Sensory Profile has 125 items and the short version contains 38 items. Parents use a Likert scale to rate how frequently their child demonstrates a particular behavior (ranging from 1 = always to 5 = never). Total scale for the Short Sensory Profile 38-190, with a lower score indicates greater deviation from typically developing children and indicates more sensory reactivity symptoms. Subscales Tactile (7-35) Taste / Smell (4-20) Movement (3-15) Sensation (7-35) Auditory (6-30) Low Energy / Weak (6-30) Visual / Auditory (5-25)
The Sensory Assessment for Neurodevelopmental Disorders (SAND)
时间窗: After 12 weeks of growth hormone therapy
a clinician-administered assessment and corresponding caregiver interview that is not dependent on verbal or cognitive ability and is therefore appropriate for severely affected or nonverbal individuals with PMS. Responses are rated by a trained examiner on an algorithm. Scores are dichotomous, 0 (not present) or 1 (present) and are based on a summary of observed sensory behaviors throughout the duration of the observation. A total SAND score ranging from 0 to 90. Higher scores represent a higher level of sensory reactivity symptoms.
次要结局
- Change in Auditory Event Related Potentials (AERP)(Baseline and 12 weeks of growth hormone therapy)
- Visual Evoked Potentials (VEP)(After 12 weeks of growth hormone therapy)
研究者
Swathi Sethuram
Fellow, Division of Pediatric Endocrinology & Diabetes
Icahn School of Medicine at Mount Sinai