SEMAFORCRANIO : Multicenter, Double-blind, Parallel, Randomized Controlled Trial of the Efficacy of Semaglutide in Hypothalamic Obesity Secondary to Craniopharyngioma in Children Aged 12 to 17 Years
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 17
- 主要终点
- Change in BMI SD score (according to french references) at 40 weeks
研究概览
简要总结
Craniopharyngioma (CP) is a rare embryonic brain tumor of the sellar and parasellar region. Despite its benign histologic characteristics, it is locally aggressive and may cause severe morbidity from invasion into adjacent tissues and structures. Hypothalamic damage due to the tumor or its management is responsible for rapid and massive obesity, one of the most severe sequelae in patients with craniopharyngioma. Current treatment of craniopharyngioma is neurosurgical, possibly completed by radiotherapy. For preventing hypothalamic damage, surgery is the most "sparing" possible for the hypothalamus, possibly completed by a highly conformation radiation treatment, such as proton beam therapy.
Despite these therapeutic advances, obesity remains a significant problem in 30 to 50% of cases today. Most studies showed that the mean BMI at diagnosis of childhood craniopharyngioma was 0.5-0.8 ± 1.5 SD score, the mean BMI gain was +2 to +3 ± 2 SD score within 3 years, with a relative stabilization or a slow increase after 3 years. When there is an anterior and posterior hypothalamic involvement (about 50% of the cases), the mean BMI gain is even higher (+4 ± 3 SD score within 3 years).
Semaglutide, a GLP1RA in weekly injection, has shown its great effectiveness for losing weight in obese adults and adolescents (mean difference in BMI change - 16.7% with semaglutide vs. placebo after 68 weeks). Preliminary data in obese children with craniopharyngioma have shown a mean 25% difference in annual BMI gain (with semaglutide treatment compared to the previous year with no semaglutide in the same children).
研究设计
- 研究类型
- 干预性
- 分配方式
- 随机
- 干预模型
- 平行分组
- 主要目的
- 治疗
- 盲法
- 四盲 (受试者、医护人员、研究者、结局评估者)
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- Age 12 to 17 years
- Treated craniopharyngioma whose last intervention was >6 months ago and whose tumor is considered stable with :
- surgical treatmentsurgery for the solid area (non-cystic portion) of the tumor was >6 months ago and whose tumor is considered stable
- irradiation treatment
- Appropriate pituitary replacements (including recombinant growth hormone replacement in case of growth hormone deficiency), as assessed by the attending child's physician, according to international recommendations.
- BMI > + 2 SD of the French references (overweight and obesity) or BMI gain ≥ + 1 SD over the past 6 to 12 months (in the absence of overweight or obesity)
- Failure to control weight despite strict adherence to dietary guidelines for at least six months (healthy nutrition and physical activity counseling provided by a dietician or other qualified healthcare professional)
- For women patients with spontaneous menarche (without the use of hormone treatment with oestrogens), highly effective contraceptive methods during all study participation (and until 7 weeks after last study drug intake)
- Subjects covered by or having the rights to medical care assurance
- Written consent signed by the parents or legally acceptable representatives of the subject, and child participation agreement
排除标准
- Other weight loss treatments within 90 days before screening
- Previous surgical treatment for obesity
- Other chronic diseases
- History of pancreatitis (acute or chronic, regardless of the number of years)
- Severe psychiatric disorder (e.g., schizophrenia, bipolar disorder)
- Mental retardation
- A lifetime history of suicidal attempt
- History of NEM2 or medullary thyroid carcinoma, malignant neoplasms/carcinomas in situ, or uncontrolled thyroid disease
- Inability to understand the study
- Major problem of compliance with existing treatments (suggesting that compliance with the protocol will be insufficient)
- Any disorder, unwillingness, or inability, not covered by any of the other exclusion criteria which, in the investigator's opinion, might jeopardize the participant's safety or compliance with the protocol
- Known or suspected abuse of alcohol or recreational drugs
- History of type 1 or type 2 diabetes
- Patient with severe renal insufficiency (eGFR < 30 mL/min/1,73m2)
- Patient with hepatic impairment (mild to severe)
- Participation in another interventional research modifying management or likely to influence the study's assessment criteria
- Pregnancy or desire of pregnancy, breast-feeding patients and parturients
研究组 & 干预措施
PLACEBO
干预措施: Placebo weekly Injection (Drug)
SEMAGLUTIDE
干预措施: Semaglutide (Wegovy) weekly injection (Drug)
结局指标
主要结局
Change in BMI SD score (according to french references) at 40 weeks
时间窗: 40 weeks
Co-primary 1 (S40 - RCT): Change in BMI (in SD for age and sex according to French references) after 40 weeks of treatment with semaglutide (dose escalation over 16 weeks followed by a maintenance dose of 2.4 mg/week for 24 weeks) compared to placebo
Change in BMI SD score (according to french references) at 80 weeks
时间窗: 80 weeks
Co-primary 2 (S80 - delayed-start): Change in BMI-SD from baseline to S80: "semaglutide group starting at S0" vs "semaglutide group starting at S40"
次要结局
- Change in BMI in kg/m at 40 weeks compared between semaglutide and placebo(40 weeks)
- Change in BMI in kg/m at 80 weeks between compared between semaglutide and placebo(80 weeks)
- Intra-individual progression of BMI-DS at each visit depending on Semaglutide treatment(80 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on height(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on weight(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on waist circumference(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on arterial blood pressure(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on fasting blood glucose(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on HbA1C(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on insulin level(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on cholesterol(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on triglycerides(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on body composition(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on bone age(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on quality of life by PedsQL questionnaire(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on quality of life by Epworth Sleepiness Scale(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on quality of life by IWQOL-Kids questionnaire(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on quality of life by Dykens Hyperphagia questionnaire(40 weeks)
- Effects of 40 weeks of weekly semaglutide treatment on quality of life by Daily Hunger Score(40 weeks)
- Safety between 2 arms(80 weeks)
- Kinetics of BMI-DS evolution(End of study V10 (106 weeks))
研究者
研究点 (17)
标识符
- NCT 编号
- NCT07845994
- 其他研究编号
- 49RC23_0307, 2024-511114-20-00
日期
- 首次提交
- (上个月)
- 首次发布
- (昨天)
- 主要完成日期
- (4年后)
- 研究完成日期
- (4年后)
- 最近核实
- (29天前)
- 最近更新
- (昨天)
监管与共享
- FDA 监管药物
- 否
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- UNDECIDED
- 是否有结果
- 否