Rare Obesity Cohorts With Food Behavioral Disorders : Better Diagnosis for Better Treatment (ObeRar)
Hypothalamic obesity (HO) is defined as obesity secondary to functional or anatomical alterations of the hypothalamus, the central organ of energy homeostasis. The causes of HO are related either to hypothalamic lesions (eg craniopharyngioma) either to genetic diseases (syndromic obesity such as Prader-Willi syndrome or monogenic non syndromic obesity such as variants on leptin/melanocortin pathway). HO, which accounts for about 5 to 10% of obesity, groups complex disorders characterized by severe obesity associated with eating disorders, cognitive and behavioral disorders, endocrine and metabolic alterations and sometimes a visual deficit, with a major impact on quality of life, morbidity and mortality. There is currently no specific treatment of HO.
Clinical management is essentially behavioral, based on daily support of eating behavior and physical activities. HO is characterized by an intense and almost permanent hunger; a satiety disorder and an obsessive interest in food.
The education regarding food intake behavior of the caregivers and relateds is critical with advices concerning the control of the access to food and the setting up of a precise food frame on the quantities, with low energetic density, and schedules. HO are complex medical situations, often refractory to current lifestyle therapies. However innovative therapies with molecules targeting the hypothalamus are emerging. The investigator's main hypothesis is that HO have alterations in eating behavior that can be improved by innovative treatments such as, for example, molecule targeting the melanocortin pathway. The response to therapy could depend on hypothalamic origin and especially on the genotype. ObeRar cohort aims to i) improve early diagnosis of HO and ii) characterize the natural history of obesity and eating disorders, the associated phenotypes and "lifestyle" profiles (physical activity, sleep, nutrition) and cardio-metabolic and neuropsychological parameters. Defining profiles will help personalize individual care management and target patients who can participate in clinical trials with innovative therapeutics. ObeRar-cohort will thus improve the early diagnosis, prognosis, medical management and innovative therapies of these particularly severe forms of rare obesities.
調査の概要
状態
条件
詳細な説明
Hypothalamic obesity (HO) is defined as a rare obesity secondary to impaired functioning of the hypothalamus nuclei, the central organ of energy and weight homeostasis. Among the causes of HO, there are those related to a hypothalamic lesion (lesional) such as craniopharyngioma (CP) or inflammatory (sarcoidosis, tuberculosis etc ..) and those called genetic, with variations in gene involved in the central regulation of energy homeostasis. The genetic causes of obesity can be either "monogenic" by mutation of genes involved in the leptin / melanocortin pathway, or "syndromic", defined by the association of obesity and other clinical signs (syndrome), especially neuropsychological traits, such as Prader-Willi syndrome (PWS) or Bardet-Biedl syndrome. PWS, which has a frequency of 1/15000 births, is one of the most well-known obesity-related syndromes. PWS is characterized by muscle hypotonia at birth, severe hyperphagia and food impulsivity, dysmorphic features, and intellectual disability with cognitive-behavioral abnormalities. Monogenic obesity involves rare clinical situations with variants in one of the genes in the MC4R pathway, which plays a pivotal role in the hypothalamic control of food intake and energy expenditure. To date, at least 10 genes directly involved in or regulating the leptin/melanocortin pathway are known: leptin (LEP), leptin receptor (LEPR), pro-opiomelanocortin (POMC), prohormone convertase 1 (PCSK1), melanocortin receptor type 4 (MC4R) and its regulator Melanocortin Receptor Accessory Protein 2 (MRAP2), single -minded homolog 1 (SIM1), brain-derived neurotrophic factor (BDNF), neurotrophic tyrosine kinase receptor type 2 (NTRK2) and more recently, adenylate cyclase 3 (ADCY3). It is of interest to mention that some genes involved in syndromic obesity, such as PWS and BBS, are also involved in the MC4R pathway.
Although HO has various pathophysiological origins, there are common linked phenotypes with the presence of severe obesity and abnormal food intake behovior, having a heavy impact on the morbidity and mortality. Obesity is multifactorial, associated with an increase in energy intake, a decrease in energy expenditure and an alteration of peripheral metabolism with abnormal organ cross-talks. People with HO have often cognitive deficits, learning difficulties and social skills disorders. These factors alter patients' quality of life. At present, there is no specific treatment of HO. Drug treatments have been proposed such as melatonin, somatostatin analogue or sympathomimetics but with limited effects on weight and feeding behavior, resulting in no prescribing recommendations given the lack of randomized studies with sufficient patient samples. Sibutramine tested in patients with lesional or genetic HO was withdrawed from the market in France since 2010 for potentially deleterious effects on the cardiovascular system. GLP 1 analogues are an interesting therapeutic approach in patients with craniopharyngioma with some efficacy on weight, but are currently dedicated for diabetic patients in France. Regarding bariatric surgery in rare and secondary obesities, the French Haute Autorité de Santé recommends that "the indication must be exceptional and discussed on a case by case basis".
So current management is essentially behavioral, based on daily support of eating behavior and physical activity. Food management requires from a very young age and during the whole life, a permanent food control, to fight against primary impulsivity of central origin, can be a cause of frustration and behavioral disorders. Indeed, the hypothalamic impairment is characterized by intense and permanent hunger, a lack of satiety and an obsession for food. The affected patients are completely overwhelmed by this addictive behavior. It is extremely difficult or impossible for the child as for the adult with this syndrome to control his dietary intake. The caregivers and relateds must therefore control access to food at home and abroad. This requires constant supervision. An early education of food in the family is essential because today it there is no possible and sustainable autonomy regarding diet for these patients.
So, if the global, specialized and multidisciplinary care is to be implemented as early as possible, from early childhood, the development of new therapeutic strategies is essential due to the severe and early obesity. In recent years, research in therapeutic innovation has developed in an interesting way in genetic obesity, in particular by targeting the melanocortin pathway. HO have various origins but have a common phenotype, that is the presence of eating disorders with hyperphagia and food impulsivity. This is responsible for weight gain which can lead to obesity, having a significant impact on the morbidity and mortality. However, no precise data are available currently on the specific phenotype of each origin, the genotype/phenotype correlation, and national medical history of OH throughout life, from birth to adulthood, as well as the associated phenotypes, are still to be precisely described.
研究の種類
入学 (予想される)
連絡先と場所
研究連絡先
- 名前：CHRISTINE POITOU-BERNERT, Professor
- 電話番号：(33)1.42.17.57.71
- メール：christine.poitou-bernert@aphp.fr
研究連絡先のバックアップ
- 名前：BEATRICE DUBERN, Professor
- 電話番号：33 (1) 44 73 64 46
- メール：beatrice.dubern@aphp.fr
研究場所
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Paris La Defense、フランス、75013
- 募集
- Pitié-Salpêtrière Hospital, AP-HP -Nutrition department
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コンタクト：
- CHRISTINE POITOU-BERNERT, MD
- 電話番号：(33)1.42.17.57.71
- メール：christine.poitou-bernert@aphp.fr
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
Population 1: Adults and children with severe obesity ie (BMI> 35 kg / m² for adults and Z BMI score> 3DS for age and sex for children) and / or eating disorders with genetic diagnosis as part of care This population will be divided into 5 groups according to the genetic diagnosis made
- Prader willi syndrome (SPW)
- syndromic obesity except prader willi (OS)
- obesity by homozygous mutation of the melanocortin pathway (HomMel)
- obesity by heterozygous mutation of the melanocortin pathway (HetMel)
- controls without genetic abnormality found in view of the final results of the genetic diagnosis(CON) Population 2: Adults and children with obesity and / or eating disorders hypothalamic lesion (craniopharyngioma example)
説明
Inclusion Criteria:
Population 1:
- Adults ≥ 18 years old with BMI> 35 kg / m² or children <18 years old with BMI Zscore> + 3DS for age and sex and / or eating behavior disorders consulting in one of the participating centers
Patient benefiting from a genetic diagnosis as part of his usual care according to criteria justifying a genetic analysis such as:
obesity with early onset (<12 years) or very severe BMI> 50 kg / m² and / or presence of eating disorders, endocrine abnormalities or other symptoms suggestive of a genetic anomaly (such as: intellectual disability, retinopathy of pigmentation or other)
- Adult patient or holders of parental authority (for children) having received the information and having signed a free, informed and written consent (or for adult patients under legal protection measure or unable to consent, information and obtaining the consent of the legal representative, the support person, or the relative / close relative).
Population 2
- Adult or child with obesity and / or eating disorder due to hypothalamic lesion (craniopharyngioma for example)
- Adult patient or holders of parental authority (for children) having received the information and having signed a free, informed and written consent (or for adult patients under legal protection measure or unable to consent, information and obtaining the consent of the legal representative, the support person, the relative / relative).
Exclusion Criteria:
- Refusing to participate in the study
- Not mastering the french language
- Safety measure
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 観測モデル：コホート
- 時間の展望：見込みのある
コホートと介入
グループ/コホート |
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Population 1
Adults and children with severe obesity ie (BMI> 35 kg / m² for adults and Z BMI score> 3DS for age and sex for children) and / or eating disorders with genetic diagnosis as part of care.
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Population 2
Adults and children with obesity and / or eating disorders hypothalamic lesion (craniopharyngioma example).
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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This criterion is the age of obesity beginning
時間枠：For adults, at inclusion. For children at inclusion and every three years (from date of inclusion until the date of first documented BMI>IOTF 30 kg/m²) (e.g from date of inclusion until the end of follow up, so 20 years)
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A BMI curve is performed using the aggregation of multiple measurements (eg weight in kg and height in meters) during childhood.
Retrospective data on height and weight collected every year form birth to the age BMI= weight/height², Obesity is defined for a BMI above the IOTF curve
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For adults, at inclusion. For children at inclusion and every three years (from date of inclusion until the date of first documented BMI>IOTF 30 kg/m²) (e.g from date of inclusion until the end of follow up, so 20 years)
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Maximum weight in kg
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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allows to define the severity of obesity
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Maximum height in m
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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allows to calculate the maximum BMI= maximum weight/(maximum height)²
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: number of calories/24h with distribution of macronutrients
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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from the dietary survey costed by a dietician with kcal/24h and repartition of % of glucids, lipids and proteins
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: binge eating behavior
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Binge eating scale (BES) (score 0-30, a score > 18 defines the presence of hyperphagia)
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: hyperphagia
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Dyckens hyperphagia questionnaire for entourage if the patient is not unable to complete questionnaires due to intellectual or other disabilities (a score>9 is considered as the limit for hyperphagia)
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: hunger and satiety before and after meals
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Score on the visual analogic scale (VAS) (min 0-max 10, a score >6 is considered as high)
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: Quantification of physical activity in minutes / day
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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count of mouvements/day measured by an accelerometer
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: waist circumference
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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a wais curcumeference greater than 102 cm (in men or greater than 88 cm ) in women is the current threshold for increased metabolic risk (caucasian population)
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: percentage of fat mass
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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DEXA
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: quantification of visceral fat in cm²
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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scan
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: Quality of life
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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the The Short Form (36) Health Survey (SF36) is as standardized questionnaire to assess quality of life.
The SF-36 yields eight scale scores and two summary scores: the physical component summary (PCS) and mental component summary (MCS) scores
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: depression and anxiety
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Hospital Anxiety and depression scale (HAD) is a questionnaire with 14 questions with a score of anxiety and a score of depression (min 0-max 21)
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: Resting energy expenditure
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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by indirect calorimetry in kcal / 24h
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: Metabolic assessment
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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this complete metabolic assessment include blood measurment of routine biomarkers : total cholesterol HDLC/LDLC triglycerid glycemia in mmol/l ; insulinemia in µU/ml ; ASAT/ALAT/ gammaGT in UI/l If at least one of this marker is above the normal range, we consider that metabolic assessment is abnormal
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: ejection fraction
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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measurements made during cardiac MRI
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: Total Intelligence quotient
時間枠：at the inclusion
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measured during the neuropsychological assessment if applicable (patient with intellectual disability) by the WAIS-IV tool , intellectual deficiency is considered if total IQ<70
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at the inclusion
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Adult: Assessment of interoceptive capacities: counting of heartbeats
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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according to validated technique (Schandry 1981) associated with metacognitive confidence measures in the counting of heartbeats (after each answer: "how confident are you in your answer"), an auto-questionnaire of interception: MAIA (translation by T Similowsky, validated by Carré 2014) an auto-questionnaire of interception: MAIA (translation by T Similowsky, validated by Carré 2014)
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Adult: Family history of obesity (parents, siblings)
時間枠：at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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maximal BMI (Body Mass index) of mother, father, sisters and brothers
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at inclusion and during follow-up evaluation visit every 5 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Children: Age of adiposity rebound (years) determined
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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on the BMI curve
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at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Children: Severity of obesity
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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BMI Zscore by age and sex
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at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Children: number of calories and distribution of macronutrients
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
from the dietary survey costed by a dietician with kcal/24h and repartition of % of glucids, lipids and proteins
|
at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
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Children: hunger and satiety before and after meals
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
Score on the visual analogic scale (VAS) (min 0-max 10, a score >6 is considered as high)
|
at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
|
Children: Quantification of physical activity in min / day
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
count of mouvements/day measured by an accelerometer
|
at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
|
Children: waist circumference
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
a waist circumference greater than 102 cm (in men or greater than 88 cm ) in women is the current threshold for increased metabolic risk (caucasian population)
|
at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
|
Children: percentage of fat mass
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
DEXA
|
at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
|
Children: Resting energy expenditure
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
by indirect calorimetry in kcal / 24h
|
at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
|
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Children: lipids, HOMA-IR, liver enzymes
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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complete metabolic assessment
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at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Children: IGF1, FT4, TSH, testosterone, vitamin D, PTH, others according to the clinical picture
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Complete endocrine assessment
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at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Children: ejection fraction
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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measurement with heart ultrasound
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at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Children: Total Intelligence quotient
時間枠：at the inclusion
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measured during the neuropsychological assessment if applicable (patient with intellectual disability) by the WAIS-IV tool , intellectual deficiency is considered if total IQ<70
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at the inclusion
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Children: Quality of life
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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SF10 completed by parents or SF36 by children over 15 years
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at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Children: Hyperphagia
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Dyckens hyperphagia questionnaire completed by parents.
(a score>9 is considered as the limit for hyperphagia)
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at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Children: Food behaviour
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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questionnaire depends on the age: (0-23 months) BEBQ (Baby Eating Behavior Questionnaire) completed by parents; (2-15 years) CEBQ (Child Eating Behaviour Questionnaire) completed by parents; TFEQ21 score completed by children ( for Children >15years)
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at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Children : over 15 years old : binge eating behavior
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Binge eating scale (BES) (score 0-30, a score > 18 defines the presence of hyperphagia)
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at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Children : over 15 years old : depression and anxiety
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Hospital Anxiety and depression scale (HAD) is a questionnaire with 14 questions with a score of anxiety and a score of depression (min 0-max 21)
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at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Children : over 15 years old : addiction
時間枠：at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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Yale Food Addiction Scale (YFAS) is a 25-point questionnaire
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at inclusion and during follow-up evaluation visit every 3 years (e.g from date of inclusion until the end of follow up, so 20 years)
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協力者と研究者
捜査官
- 主任研究者：CHRISTINE POITOU-BERNERT, Professor、Assistance Publique - Hôpitaux de Paris
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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