Octreotide Therapy in Children and Young Adults With Prader-Willi Syndrome (PWS)

• Fasting total ghrelin, hunger and food intake as measured by hunger and hyperphagia by questionnaires, parent-reported 72-hour food recall, weight, height, BMI, skin-fold measurements. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  

• Body-composition as measured by DEXA scan, the BOD POD body composition tracking system and bioelectrical impedance analysis (BIA). We will also measure resting metabolic rate, and hormone levels related to weight management. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  

Drug: Octreotide
Octreotide or placebo to be administered by subcutaneous injection three times daily
Other Name: Sandostatin

Obesity continues to be a prevalent health concern affecting every race of the American population. According to data from the World Health Organization, 54% of U.S. adults are overweight (body mass index (BMI) >25 kg/m2 ) and 22% are obese (BMI >30 kg/m2) (1). In addition, 25% of U.S. children are overweight or obese (1). Studies show that obese children are likely to become obese adults (2-5). Also, recent studies report significant years of life lost due to the impact of being an obese adult (6, 7). Thus, insights into the pathogenesis of childhood obesity and preventative measures are needed to combat the inevitable increase in worldwide incidence of obesity and its associated co-morbidities. Recent studies have identified a new gastroenteric hormone, ghrelin, as a long-term regulator of energy balance in humans (12). Ghrelin is a 28 amino acid acylated peptide which is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), a hypothalamic G-protein-coupled receptor (13). Enteroendocrine cells (X/A-like cells) of the stomach are the major site of ghrelin synthesis, although a minor proportion of ghrelin synthesis occurs in other sites such as the hypothalamus, pituitary, duodenum, jejunum and lung (14) (15, 16).

The hypothesis that hyperghrelinemia causes some of the features of PWS predicts that this disorder will be ameliorated (partially or completely) by lowering ghrelin levels. We have recently shown that the somatostatin agonist, octreotide, suppresses ghrelin levels in humans. If octreotide remains effective in longer term studies, the drug may become an adjuvant therapy, in addition to growth hormone, to control the insatiable appetite and morbid obesity seen in this condition.