ObesityObeRarNCT04604626
Rare Obesity Cohorts With Food Behavioral Disorders : Better Diagnosis for Better Treatment
An observational study of Obesity, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Obesity
- How many people
- 10,000 participants
- Where
- 1 siteFrance
- Study dates
- 10 Jun 2020to 1 Jul 2040
- How long will I take part?
- 20 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: 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)
Who may be able to join
- 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).
Who cannot join
- Refusing to participate in the study
- Not mastering the french language
- Safety measure
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Pitié-Salpêtrière Hospital, AP-HP -Nutrition department
La Defense, 75013
CHRISTINE POITOU-BERNERT, MD, (33)1.42.17.57.71, christine.poitou-bernert@aphp.fr
About this study
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.
Read the detailed description
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.
- Conditions
- Obesity
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. | |
| Population 2 | Adults and children with obesity and / or eating disorders hypothalamic lesion (craniopharyngioma example). |
What is being measured
The primary outcome is the main question the study is designed to answer.
This criterion is the age of obesity beginning
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
Measured: 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)
Secondary outcomes (36)
Maximum weight in kg
allows to define the severity of obesity
Measured: 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)
Maximum height in m
allows to calculate the maximum BMI= maximum weight/(maximum height)²
Measured: 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)
Adult: number of calories/24h with distribution of macronutrients
from the dietary survey costed by a dietician with kcal/24h and repartition of % of glucids, lipids and proteins
Measured: 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)
Adult: binge eating behavior
Binge eating scale (BES) (score 0-30, a score > 18 defines the presence of hyperphagia)
Measured: 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)
Adult: hyperphagia
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)
Measured: 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)
Adult: hunger and satiety before and after meals
Score on the visual analogic scale (VAS) (min 0-max 10, a score >6 is considered as high)
Measured: 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)
Adult: Quantification of physical activity in minutes / day
count of mouvements/day measured by an accelerometer
Measured: 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)
Adult: waist circumference
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)
Measured: 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)
Adult: percentage of fat mass
DEXA
Measured: 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)
Adult: quantification of visceral fat in cm²
scan
Measured: 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)
Adult: Quality of life
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
Measured: 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)
Adult: depression and anxiety
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)
Measured: 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)
Adult: Resting energy expenditure
by indirect calorimetry in kcal / 24h
Measured: 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)
Adult: Metabolic assessment
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
Measured: 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)
Adult: ejection fraction
measurements made during cardiac MRI
Measured: 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)
Adult: Total Intelligence quotient
measured during the neuropsychological assessment if applicable (patient with intellectual disability) by the WAIS-IV tool , intellectual deficiency is considered if total IQ<70
Measured: at the inclusion
Adult: Assessment of interoceptive capacities: counting of heartbeats
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)
Measured: 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)
Adult: Family history of obesity (parents, siblings)
maximal BMI (Body Mass index) of mother, father, sisters and brothers
Measured: 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)
Children: Age of adiposity rebound (years) determined
on the BMI curve
Measured: 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: Severity of obesity
BMI Zscore by age and sex
Measured: 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: number of calories and distribution of macronutrients
from the dietary survey costed by a dietician with kcal/24h and repartition of % of glucids, lipids and proteins
Measured: 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: hunger and satiety before and after meals
Score on the visual analogic scale (VAS) (min 0-max 10, a score >6 is considered as high)
Measured: 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
count of mouvements/day measured by an accelerometer
Measured: 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
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)
Measured: 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
DEXA
Measured: 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
by indirect calorimetry in kcal / 24h
Measured: 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: lipids, HOMA-IR, liver enzymes
complete metabolic assessment
Measured: 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: IGF1, FT4, TSH, testosterone, vitamin D, PTH, others according to the clinical picture
Complete endocrine assessment
Measured: 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: ejection fraction
measurement with heart ultrasound
Measured: 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: Total Intelligence quotient
measured during the neuropsychological assessment if applicable (patient with intellectual disability) by the WAIS-IV tool , intellectual deficiency is considered if total IQ<70
Measured: at the inclusion
Children: Quality of life
SF10 completed by parents or SF36 by children over 15 years
Measured: 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: Hyperphagia
Dyckens hyperphagia questionnaire completed by parents. (a score>9 is considered as the limit for hyperphagia)
Measured: 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: Food behaviour
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)
Measured: 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 : over 15 years old : binge eating behavior
Binge eating scale (BES) (score 0-30, a score > 18 defines the presence of hyperphagia)
Measured: 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 : over 15 years old : depression and anxiety
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)
Measured: 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 : over 15 years old : addiction
Yale Food Addiction Scale (YFAS) is a 25-point questionnaire
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2020
- Study start10 Jun 2020
- Primary completion1 Jul 2022 (estimated)
- Study completion1 Jul 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10,000 participants (estimated)
- Target duration
- 20 Years
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- CHRISTINE POITOU-BERNERT, Professor, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04604626
- Sponsor's protocol ID
- APHP200181
- Other IDs
- 2019-A03201-56
- Acronym
- ObeRar
- Status last verified
- Mar 2020
- First submitted
- 7 Apr 2020
- Last updated
- 27 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rare Obesity Cohorts With Food Behavioral Disorders : Better Diagnosis for Better Treatment
- ClinicalTrials.gov ID
- NCT04604626
- Acronym / sponsor ID
- ObeRar / APHP200181
- Conditions
- Obesity
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 10,000 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 10 Jun 2020 (actual)
- Primary completion
- 1 Jul 2022 (estimated)
- Study completion
- 1 Jul 2040 (estimated)
- First posted
- 27 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 20 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
| Population 2 | – | –Adults and children with obesity and / or eating disorders hypothalamic lesion (craniopharyngioma example). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 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)
Key inclusion criteria (8 listed)
- Population 1:
- 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)
- Population 2
Key exclusion criteria (3 listed)
- Refusing to participate in the study
- Not mastering the french language
- Safety measure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
This criterion is the age of obesity beginning
Time frame: 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)
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
36 secondary outcomes
Maximum weight in kg
Time frame: 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)
Maximum height in m
Time frame: 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)
Adult: number of calories/24h with distribution of macronutrients
Time frame: 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)
Adult: binge eating behavior
Time frame: 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)
Adult: hyperphagia
Time frame: 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)
Adult: hunger and satiety before and after meals
Time frame: 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)
Adult: Quantification of physical activity in minutes / day
Time frame: 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)
Adult: waist circumference
Time frame: 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)
Adult: percentage of fat mass
Time frame: 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)
Adult: quantification of visceral fat in cm²
Time frame: 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)
Adult: Quality of life
Time frame: 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)
Adult: depression and anxiety
Time frame: 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)
Adult: Resting energy expenditure
Time frame: 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)
Adult: Metabolic assessment
Time frame: 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)
Adult: ejection fraction
Time frame: 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)
Adult: Total Intelligence quotient
Time frame: at the inclusion
Adult: Assessment of interoceptive capacities: counting of heartbeats
Time frame: 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)
Adult: Family history of obesity (parents, siblings)
Time frame: 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)
Children: Age of adiposity rebound (years) determined
Time frame: 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: Severity of obesity
Time frame: 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: number of calories and distribution of macronutrients
Time frame: 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: hunger and satiety before and after meals
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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: lipids, HOMA-IR, liver enzymes
Time frame: 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: IGF1, FT4, TSH, testosterone, vitamin D, PTH, others according to the clinical picture
Time frame: 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: ejection fraction
Time frame: 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: Total Intelligence quotient
Time frame: at the inclusion
Children: Quality of life
Time frame: 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: Hyperphagia
Time frame: 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: Food behaviour
Time frame: 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 : over 15 years old : binge eating behavior
Time frame: 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 : over 15 years old : depression and anxiety
Time frame: 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 : over 15 years old : addiction
Time frame: 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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
CHRISTINE POITOU-BERNERT, Professor principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obesity, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact CHRISTINE POITOU-BERNERT, Professor ((33)1.42.17.57.71, christine.poitou-bernert@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
This criterion is the age of obesity beginning (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2020.