A Personalized Program of Physical Activity and Diet for Hypothalamic Obesity
Condition: Hypothalamic Obesity
MeSH terms: Obesity
Study type: Observational

Summary: 
      Hypothalamic obesity (HO) is an obesity secondary to an alteration of the functioning of the
      hypothalamus, the central organ of energy homeostasis. The causes of OH are related to an
      hypothalamic lesion (eg craniopharyngioma) or to genetic diseases (ex: Prader-Willi
      syndrome). OH, which accounts for about 5 to 10% of obesity, is a complex handicap
      characterized by severe obesity associated with eating disorders, cognitive and behavioral
      disorders and sometimes a visual deficit, with a major impact on quality of life, morbidity
      and mortality. There is currently no specific treatment of HO. Management is essentially
      behavioral, based on daily support of eating behavior and physical activities (PA). OH is
      characterized by an intense and almost permanent hunger felt, a satiety disorder and an
      obsessive interest in food. The food education of the entourage is essential, the advise
      concern 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. OH is characterized by obesity with
      lean mass deficit. PA must therefore be regular, adapted to the disability and personalized
      to take into account cognitive deficits and behavioral disorders. Although the supervision of
      meals and daily PA is now recognized as fundamental in the care of these patients (National
      Program of Diagnosis and Care established by the French "Haute Autorité de Santé"), few
      studies have evaluated the effectiveness of programs with personalized support on global
      health. The investigators hypothesize that a personalized 4-month individual home-based
      counseling program on dietary counseling and PA can be effective to modify behaviors such as
      diet and PAs with an impact on changing weight and quality of life. The 16-week program
      includes a dietetic component (initial assessment with dietary care plan followed by a
      30-minute telephone interview every month with dietician) and a PA component (two 1-hour
      individualized sessions, performed at home and supervised by a PA educator). Before and after
      the program, the investigators will evaluate habitual PA with an accelerometer, feeding
      behavior, physical functioning, weight change, body composition, quality of life and will
      constitute a biobank of serums, adipose tissues and stools. If the effectiveness of this
      program is demonstrated this will help to find ways to sustain this support by the
      institutions, to train professionals in the complex accompaniment of these patients. Finally
      this program set up as part of a rare disease can show the benefits in other populations of
      more common pathology (common severe obesity, intellectual disability, behavioral disorders).
    

Detailed description: 
      Hypothalamic obesity (HO) is defined as obesity secondary to impaired functioning of the
      hypothalamus nuclei, the central organ of energy and weight homeostasis. Among the causes of
      OH, there are those related to a hypothalamic lesion (lesional) such as craniopharyngioma
      (CP) or inflammatory (sarcoidosis, tuberculosis etc ..) and those called genetic, with gene
      abnormalities 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), such as Prader-Willi syndrome (PWS). PWS, which has a frequency of 1/15000
      births, is one of the most well-known obesity-related syndromes. It is characterized by
      muscle hypotonia at birth, severe hyperphagia and dietary impulsivity, dysmorphic features,
      and intellectual disability with cognitive-behavioral abnormalities.

      Although HO has various origins, it has a common phenotype with the presence of severe
      obesity, 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. First, impaired functioning of the hypothalamic nuclei
      leads to resistance to leptin and other hormones involved in the energy balance (GLP1,
      ghrelin etc.) leading to an increase in hunger and a lack of satiety responsible for
      hyperphagia. An alteration of the cognitive control of food intake and a hyper activation of
      the reward system have also been described in PWS, which can explain episodes of uncontrolled
      food impulsivity (food theft) and a high sensitivity to external stimuli in particular
      visualization of food. As such, it is a particularly interesting model for studying
      hyperphagia and alterations in the control of food intake. It should be noted that eating
      disorders vary from one individual to another but can also fluctuate for the same individual
      depending on the psychological state of the patients and their daily activities. The
      involvement of the autonomic nervous system leads to a decrease in the sympathetic tone
      responsible for a fall in resting energy expenditure. Indeed, there is a positive correlation
      between autonomic nervous system activity, basal metabolism, and spontaneous physical
      activity. In addition, endocrine deficits, present in HO, not or insufficiently substituted,
      such as gonadotropic, thyrotropic or somatotropic insufficiency have also a negative impact
      on resting energy expenditure. The total energy expenditure is also lowered by the low
      spontaneous physical activity (PA) of the patients in relation to the hypotonia described in
      these patients and a reduction of the spontaneous activation of the movements. In addition,
      sleep disorders (OSA, narcolepsy, daytime hypersomnolence) are common in patients with OH and
      may increase exercise fatiguability and difficulties for patients to do PA. Finally, visual
      disturbances (reduction of severe visual acuity by amputation of the visual field) associated
      with optic chiasm involvement in lesion-induced HO or induced by craniopharyngioma tumor
      resection, are also a limitation for PA and increase sedentary lifestyle. The absence of PA
      and the increase in sedentary lifestyle are associated with abnormal body composition with an
      increase in body fat at the expense of muscle mass . This is especially important in patients
      with PWS associated with developmental muscle hypotonia].

      People with HO have often cognitive deficits, learning difficulties and social skills
      disorders. These are constant in the PWS but also in the lesional cause. All these factors
      lead to altering the quality of life. Thus, an impairment of quality of life has been
      demonstrated in 185 obese patients with craniopharyngioma in childhood. In our cohort of HO
      subjects, mood disorders assessed by the HAD score are common: 91% for lesional HO 50% for
      genetic HO and this is correlated with BMI. The Kendall-Taylor study shows that, in children
      with craniopharyngioma, the quality of life score depends on the age at diagnosis, the
      presence of somatotropic deficiency and BMI. 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, withdrawn from the
      market in France since 2010 for potentially deleterious effects on the cardiovascular system.
      GLP 1 analogues are also an interesting therapeutic approach in patients with
      craniopharyngioma with some efficacy on weight , but are currently reserved for diabetic
      patients. Regarding bariatric surgery, the HAS recommends that "the indication must be
      exceptional and discussed on a case by case basis". A meta-analysis of the results of
      bariatric surgery in 21 subjects with craniopharyngioma showed a weight loss at 1 year of
      15.1 kg, in the same average as the obese general population operated. Nevertheless the
      subjects were selected (absence of important behavioral disorders) and the results concern
      only the short term. In genetic HO, especially PWS, the results of bariatric surgery should
      be used with caution. In terms of weight loss, the results are not as good, with medium-term
      weight regain, persistence of hyperphagia despite the reduction of the gastric pouch, and an
      increased risk of morbidity and mortality. Management is essentially behavioral, based on
      daily support of eating behavior and PA. Food management requires from a very young age for
      these patients, a permanent food control, to fight against primary impulsivity of central
      origin, can be a cause of frustration and behavioral disorders. Indeed, the genetic syndrome
      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 entourage 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. There is a strong need for coherence for caregivers to avoid unnecessary
      discussions and arguments. It is necessary to inform, prevent, associate the family and
      friendly entourage so that there is a coherence with the line of conduct chosen by all.
      Patients can not feel the signals that would allow them to have a meal like other people, so
      it is recommended to put in place a precise food frame on quantities and schedules, a low
      energy density food setting while providing sufficient food volume. A strict framework
      reassures and secures the patient because he has benchmarks. This is to reassure the person
      himself, to do everything possible to limit the temptations that are a source of tantrums and
      frustration. By respecting meal schedules and their composition ("food security"), by
      diverting patients' thinking, by occupying them, we can improve the food obsession of
      patients with HO. This specific and personalized dietary management is therefore necessary
      and essential. Physical activities are also a basic component of treating common obesity and
      its complications. It has a favorable effect on weight control, especially on the prevention
      of weight gain. In addition, PA has important beneficial effects on body composition.
      Regardless of weight loss, PA decreases total body fat and visceral abdominal fat. It also
      limits the loss of muscle mass during weight loss. Beyond its effects on weight control and
      body composition, PA is beneficially associated with many health parameters and decreases the
      risk of developing the major complications of obesity (type 2 diabetes and cardiovascular
      diseases). PA is also associated with an increase in quality of life. Finally, PA improves
      physical capacity that is often greatly diminished in obese subjects. Obesity is associated,
      on the one hand, with a decrease in cardiorespiratory fitness, muscular strength, functional
      capacity (observed for example during the 6-minute walk test) and, on the other hand,
      impaired balance and locomotion. Studies in patients with HO showed that patients had a low
      level of PA. Only one study measured PA level in the PWS. PA was measured using
      accelerometers in 28 young adults with moderate obesity. Only 25% of men and 15% of women
      achieved the minimum level of recommended PA and the average daily duration of moderate to
      high intensity AP was 14 minutes. Two studies measured PA level using accelerometers or
      pedometers in patients with craniopharyngioma. PA level was lower than that seen in normal
      weight subjects. In addition, the functional capacity of HO subjects appears to be impaired.
      For example, muscle strength, balance, and locomotion were assessed in 5 studies of 12 to 19
      young adults with PWS and massive obesity. Muscle strength was significantly reduced compared
      to normal weight subjects, but also compared to control obese subjects. The balance was also
      altered, increasing the risk of falling. Finally, these patients adopted a different walking
      pattern (decreased walking speed and step length, increased double support time). Grolla et
      al. showed that a 4-week program, repeated 4 times a year, combining a low-calorie diet and a
      sustained program of PA (up to 7 hours of activities per day, such as walking, exercise bike
      , carpet exercises) reduced BMI of 2.5 kg / m2 and body fat by 2.5 kg in patients with PWS.
      Two other studies evaluated the effect of a PA program combining an initial stay of 2 weeks
      and a home-based training program for 6 months. During the initial 2 weeks, patients
      participated in 4 sessions per week, supervised by trained staff, during which they performed
      strength training and endurance exercises. During the following 6 months at home, patients
      autonomously performed 3 sessions per week of muscle strengthening. This program resulted in
      improved biomechanical parameters of the ankle and knee during walking. Other measured
      parameters (muscle strength, balance) were unchanged. Another study followed patients with
      PWS for 7 years during which patients regularly participated in rehabilitation programs
      combining PA, dietary management and physiotherapy. The results showed an improvement in the
      biomechanical parameters of gait. Thus, the management of HO should be comprehensive,
      residing in the control of the environmental risk factors of weight gain: management of
      hyperphagia by regular and personalized nutritional and dietary monitoring and appropriate
      medico-social support (educator, informed parents). Compulsive eating behavior can be reduced
      in a structured environment, with support and stimulation of other interests (especially
      physical activities and activities). In addition, a daily PA is essential to compensate for
      the decreased basic metabolism (see above). If support by PA and food management is now
      recognized as a fundamental element of the care of patients suffering from HO (National
      Program of Diagnosis and Care established by the HAS (Haute Autorité de Santé) http: //
      www.has-sante.fr/portail/upload/docs/application/pdf/2012-06/ald_hors_liste_-_pnds_on_the_syn
      drome_de_prader-willi.pdf), no study has evaluated the effectiveness of a personalized
      support program, framed and at home, focusing on dietary counseling, control of eating
      behavior and PA, on dietary behavior, patients' health status, physical activity volume and
      functional capacity, the evolution of weight and quality of life.

      The hypothesis of the investigators is that a personalized home-based support program for
      dietary advice and PA for 4 months helps to change weight changes through behavioral changes
      such as increasing habitual physical activity, improving eating behavior, functional capacity
      and quality of life.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Adults with hypothalamic obesity (lesional or genetic)
      
Keywords: Hypothalamic obesity; Prader-willi syndrome; Physical activity