Active clinical trials for "Prader-Willi Syndrome"

To evaluate the effectiveness of rhGH (Recombinant human growth hormone) injection for improving motor development in patients with PWS.

Prader-Willi Syndrome (PWS) is a multisystemic genetic disease characterized by hypotonia, mental retardation, hyperphagia, and uncontrollable hunger due to hypothalamic dysfunction, caused by dysregulation of genes located in chromosome 15q11-q13. The goal of this study is to evaluate the effects of Transcranial Direct Current Stimulation (tDCS) on hyperphagia and behavior in PWS. Forty children and adolescents (11-24 years) with clinical and cytogenetic-molecular diagnosis of Prader-Willi syndrome will be assessed before and after 10 tDCS session with: Food Craving Questionnaire (FCQ), Aberrant Behavior Checklist (ABC), Dykens hyperphagia questionnaire. Caregivers self-reported the participant's behaviors at home and, lately, they will be categorized and quantified. tDCS will be applied for 20 minutes with electrodes of 25cm2 wrapped in cotton material soaked in saline solution. The anode at the left dorsolateral prefrontal cortex (F3) and the cathode at the contralateral area (F4). Children from 11-12 years will receive a current of 1mA; above 13 years, 2mA.

Adults aged over 18 years, with the diagnosis of Prader-willi syndrome will be recruited through the hospital's outpatient clinic for either as intervention group receiving therapeutic elastic band training, or as control group receiving usual care for a total of 16 weeks. Body composition, physical capacity, and serum changes will be assessed before and after the intervention.

The purpose of this study is to determine presence of central adrenal insufficiency in children with Prader Willi Syndrome using low dose (1 mcg) ACTH stimulation test compared to results of overnight metyrapone test.

There is currently no drug with pediatric marketing authorization capable of limiting the advance in bone maturation of children with aggressive adrenarche. Estrogens are the principal actors involved in bone maturation and premature epiphyseal fusion. Aromatase inhibitors, used for the treatment of hormone-dependent cancers, block the transformation of androgens into estrogens. Third generation inhibitors, of which Anastrozole is one, appear to be well tolerated in children and are sometimes used within the framework of clinical trials to limit bone maturation and improve prognosis with respect to final size, notably in children treated with growth hormone (GH) due to a GH deficit. Nevertheless, the data reported are based on small sample sizes and do not include children with pathological adrenarche.

Introduction: The prevalence and clinical significance of central adrenal insufficiency (CAI) in adult patients with Prader Willi Syndrome (PWS) remains unclear. Aim: To assess the prevalence of CAI in adults with PWS and to analyse the effects of replacement therapy with hydrocortisone (HCT) in patients with suspected CAI. Material and Methods: Twenty one adult patients with PWS were evaluated. Based on peak cortisol at the 30 minute of the high dose short Synacthen test (HDSST), patients were divided into three groups: CAI (central adrenal insufficiency) - peak cortisol <500nmol/L, intermediate (partial AI) - peak cortisol ≥500 nmol/L and <600 nmol/L and AS (adrenal sufficiency) - peak cortisol ≥ 600 nmol/L. In patients with diagnosed CAI HCT replacement treatment was initiated. Body weight, body fat percentage, signs, and symptoms of CAI were evaluated after 6 and 12 months of treatment.

Context: Adiponectin is an adipose tissue-derived hormone with an insulin sensitizing effect, and has been related to obstructive sleep apnea syndrome. In addition, children with Prader-Willi syndrome (PWS) suffer from excessive daytime sleepiness and the abnormality of rapid eye movement (REM) sleep. Objective: To determine if the sleep stages are related to the plasma levels of adiponectin, resistin, and RBP4 (retinol binding protein-4), and whether these relationships are influenced by age, obesity and insulin resistance.

Post exercise irisin levels in PWS patients Obesity, short stature, hypogonadism, hypotonia and impaired cognition are the major clinical features of Prader-Willi syndrome (PWS), a complex neurogenetic disorder due to lack of expression of paternal genes in the chromosomal region 15q11-13. Abnormal body composition with decreased muscle mass and increased fat mass contributes to low resting energy expenditure in PWS. Severe caloric restriction in the range of 800 kcal per day along with daily exercise regimens are needed to prevent weight gain and complications of obesity in this population. Brown adipose tissue (BAT) once thought to be present only in infants, but now known to be present in adults as well, differs from the more abundant white adipose tissue (WAT) by dissipating energy through thermogenesis as a result of increased activity of the mitochondrial uncoupling protein (UCP-1). Recently evidence shows that exercise activates mitochondrial UCP-1 in subcutaneous WAT cells resulting in conversion of WAT to BAT-like adipocytes (Beige or BRITE adipose tissue). Various factors including natriuretic peptides, interleukin-6 and myokines (irisin, fibroblast growth factor 21, and ß-aminoisobutyric acid) appear to mediate the effects of exercising muscle on subcutaneous adipocytes. Decreased amount and/or activity of BAT might contribute to the lower energy expenditure and extreme difficulty in weight-control in PWS. Lower levels or decreased myokine production could result in failure to convert subcutaneous WAT to Beige or BAT-like adipocytes, and therefore minimize or negate the otherwise beneficial metabolic effects of exercise. Direct measurement of peak oxygen uptake in PWS adults show that this population has markedly lower VO2 values compared with normal BMI-matched controls. BAT activity in vivo can be accurately measured only by performing PET/CT scans which include administrating radioactive tracers. For ethical reasons, direct assessment of BAT is not possible for purposes of clinical research in PWS individuals. The investigators propose to study humoral responses to exercise in 16 (8 males) PWS adolescents and young adults and compare results with responses in a similar number of sex, age, and BMI-matched controls. At an initial one-hour meeting study participants will learn to perform aerobic (treadmill) exercise and resistance training under the supervision of an experienced exercise physiologist. Exercise intensity will be assessed by direct measurement of VO2 max. On a different day, a blood sample will be drawn before and immediately at the conclusion of the same exercise regimen. Blood samples will be assayed for irisin, interleukin-6, atrial natriuretic peptide, FGF-21, in addition to glucose, growth hormone, cortisol, norepinephrine, and lactate. The investigators hypothesize that PWS participants will show weaker humoral responses to similar exercise regimens compared to normal control subjects. Data showing lower levels of myokines, such as irisin, following exercise in PWS might suggest that inadequate conversion of WAT to BAT-like adipocytes in subcutaneous adipose tissue results in decreased thermogenesis and abnormally low energy expenditure in this population. Potentially, development of pharmacologic agents which mimic irisin or other myokines by activating UCP-1 and converting WAT to BAT-like adipocytes could offer a new approach to weight-control in PWS individuals.

The lack of serum markers that can be used to identify the levels of steatosis in obese subjects, or that can indicate a rapid progression of the metabolic disease, in which it is very often difficult to perform analyzes with imaging techniques, limits the current evolution from a generalized medicine to a personalized medicine. With the project proposal the aim is to identify serum markers for the characterization of steatosis in subjects affected by genetic obesity, which will most likely also be used in metabolic obesity.

The PWS is a genetic disease with intellectual disabilities associated with multiple manifestations in other body systems. It is characterized by hypothalamic-pituitary abnormalities with severe hypotonia during the early years of life, conditioning feeding difficulties. Hyperphagia appears later, causing severe obesity in pre - school ages. Other endocrine abnormalities associated produce short stature, GH deficiency and hypogonadotropic hypogonadism. These patients also have varying cognitive dysfunction associated as well as learning problems, compounded by the development of psychological-psychiatric and behavioral problems language. The aetiology of GH decreased secretion of the SPW is controversial, it is known that IGF -1 levels are reduced in children and adults with PWS. The rational use of GH is derived from knowledge of comorbidities observed in PWS, which seem to be related to GH deficiency: hypotonia, altered body composition, decreased growth, even obesity. • The GH is accepted since 2000 for the treatment of PWS. Following fatal episodes in our country, it was decided to start treatment at 2 years of age in an arbitrary manner, but not in the U.S. or France. Subsequent studies have found that GH per se is not a risk factor for mortality. The currently published data supporting the benefits of GH treatment when started between 4 and 6 months of life, even some experts advocate starting at 3 months, but due to the lack of consensus on the age of onset treatment, despite the benefits of your home at an early age before the onset of obesity often starts around 2 years of life. HYPOTHESIS The use of GH is safe and effective in patients with PWS children under 2 years old.