A Multicenter Pharmacoepidemiological Cohort on Real Life Use of Semaglutide in Adolescents or Adults With Monogenic Obesity
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 175
- 试验地点
- 4
- 主要终点
- Change in weight and Body Mass Index (BMI)
研究概览
简要总结
Rare genetic forms of obesity, so called monogenic obesity are linked to alteration in energy balance involving hypothalamic pathways.
More than 60 genes encoding for proteins located in the hypothalamic leptin/melanocortin pathway have been described in the French National Protocol for Diagnostic and Care (PNDS).
While pathogenic and likely pathogenic variants in these genes are well-established causes of monogenic obesity, current evidence supports a broader genetic architecture of obesity, better understood as a continuum ranging from rare high-impact variants to polygenic susceptibility.
Variants of uncertain significance (VUS) as well as variants currently classified as benign or likely benign are frequently identified in clinical practice, and their classification may evolve over time as genomic databases expand and functional data accumulate In addition, polygenic background may interact with rare variants and contribute to the severity of the phenotype, disease progression, and therapeutic response.
The natural history of monogenic obesity is characterized by an early onset in childhood, with a major increase in weight in adolescence and young adulthood. The worsening of obesity exposes these patients to severe complications.
Severe obesity and eating disorders have a major impact on the quality of life of the person but also of the family and caregivers. Clinical management is complex and requires comprehensive, specialized and multidisciplinary management. The usual lifestyle approaches have so far shown disappointing results, similarly to bariatric surgery which leads to a more frequent weight regain in the situation of monogenic obesity, justifying new approaches.
In this context, evaluating the response to treatment in the particular condition of monogenic obesity is crucial to propose therapeutic options as early as possible to limit weight evolution and its complications.
GLP-1 (glucagon-like peptide 1) based innovative therapies have recently emerged as a promising option for treatment of obesity and its complications. This is the case for Semaglutide marketed as OZEMPIC® and WEGOVY®, developed by Novo Nordisk. However, there is a lack of data to confirm that semaglutide could be also effective in monogenic obesity.
The aim of the ObGeSema project is to set up a cohort composed of patients (1) having already initiated a treatment and (2) newly treated by Semaglutide in 21 pediatric and adult Specialized Obesity Centres (CSOs) and describe their evolution over a 4 years follow-up.
详细描述
Rare genetic forms of obesity, so called monogenic obesity are linked to alteration in energy balance involving hypothalamic pathways. More than 60 genes encoding for proteins located in the hypothalamic leptin/melanocortin pathway have been described in the French National Protocol for Diagnostic and Care (PNDS) https://www.has-sante.fr/jcms/p\_3280217/fr/generique-obesites-de-causes-rares).
While pathogenic and likely pathogenic variants in these genes are well-established causes of monogenic obesity, current evidence supports a broader genetic architecture of obesity, better understood as a continuum ranging from rare high-impact variants to polygenic susceptibility.
Variants of uncertain significance (VUS) as well as variants currently classified as benign or likely benign are frequently identified in clinical practice, and their classification may evolve over time as genomic databases expand and functional data accumulate In addition, polygenic background may interact with rare variants and contribute to the severity of the phenotype, disease progression, and therapeutic response.
The natural history of monogenic obesity is characterized by an early onset in childhood, with a major increase in weight in adolescence and young adulthood. The worsening of obesity exposes these patients to severe complications. Severe obesity and eating disorders have a major impact on the quality of life of the person but also of the family and caregivers. Clinical management is complex and requires comprehensive, specialized and multidisciplinary management. The usual lifestyle approaches have so far shown disappointing results, similarly to bariatric surgery which leads to a more frequent weight regain in the situation of monogenic obesity, justifying new approaches.
In this context, evaluating the response to treatment in the particular condition of monogenic obesity is crucial to propose therapeutic options as early as possible to limit weight evolution and its complications.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients (≥12 years) having already initiated a treatment with SEMAGLUTIDE (regardless of the context: early access, routine care, self-financing, or exceptional reimbursement) or with a physician's decision to initiate treatment in the standard care. All patients having initiated treatment will be proposed to participate, including those having already stopped the treatment at the time of study initiation.
- •Confirmation of monogenic obesity, as practiced in clinical routine, regardless of current classification (i.e., pathogenic, likely pathogenic, variant of uncertain significance [VUS], or benign) in a gene with leptin-melanocortin pathway described in PNDS (https://www.has-sante.fr/jcms/p_3280217/fr/generique-obesites-de-causes-rares). ) For patients with VUS or benign variants, inclusion is conditional on the availability of a polygenic risk score (PRS)
- •Patients duly informed and not objecting to participate in the study. For patients ≥12 years <18 years Parents duly informed and not objecting that their child taking part in the study
- •Patients affiliated to a social security scheme or State Medical Assistance (AME).
排除标准
- •Pregnant and breastfeeding women
结局指标
主要结局
Change in weight and Body Mass Index (BMI)
时间窗: From baseline (T0) to T12
Percentage of subjects with a change in weight and Body Mass Index (BMI).Weight will be measured at initiation and at 12 months of the Semaglutide treatment
次要结局
- Reduction of body weight equal to or above 5%(From baseline (T0) to 6 and/or 12 and/or 24 and/or 36 and/or 48 and/or 60 months)
- Change in eating behaviour measured by the Binge Eating Scale (BES)(From baseline (T0) to 12 months)
- Change in Digestive disorders (GIQLI )(From baseline (T0) to 12 and/or 24 and/or 36 and/or 48 and/or 60 months)
- Change in score of quality of life scores (patient and parents)(From baseline (T0) to 12 months)
- Change in anxiety and depression score(From baseline (T0) to 12 and/or 24 and/or 36 and/or 48 and/or 60 months)
- Change in Hunger score(From baseline (T0) to 12 and/or 24 and/or 36 and/or 48 and/or 60 months)
- Change in eating behaviour measured by Food Craving questionnaire(From baseline (T0) to 12 months)
- Change in eating behaviour measured by the Dykens questionnaire(From baseline (T0) to 12 months)
- Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)(From baseline (T0) to 6 and/or 12 and/or 24 and/or 36 and/or 48 and/or 60 months)
- Change in eating behaviour measured by the Dutch Eating Behaviour Questionnaire (DEBQ)(From baseline (T0) to 12 months)
- Change in the International physical activity questionnaire (IPAQ - short form)(From baseline (T0) to 12 months)
- Change in sleep disorder (MCTQ score)(From baseline (T0) to 12 months)
- Change in weight and Body Mass Index (BMI)(From baseline (T0) to 6 and/or 24 and/or 36 and/or 48 and/or 60 months)
- Change in eating behaviour measured by the Child Eating Behaviour Questionnaire (CEBQ)(From baseline (T0) to 12 months)