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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Investigation of the Developmental, Nutritional and Hormonal Regulation of Ghrelin in Children and Young Adults With Prader-Willi Syndrome (PWS): Octreotide Intervention S

Brief Summary: The purpose of this study is to investigate over a 6 month period the effect of octreotide therapy on food intake, sense of hunger, body weight, body composition, efficiency of burning calories, biomarkers of weight regulation and growth hormone markers in children and young Adults with Prader-Willi Syndrome(PWS).

Detailed Summary:

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.


Sponsor: Duke University

Current Primary Outcome:

  • Number of Participants With Decrease in Fasting Total Ghrelin [ Time Frame: 6 months ]
    Number of participants showing a decrease in Fasting total ghrelin from baseline to 6 months of treatment with Octreotide or placebo
  • Number of Participants With Decrease in Weight From Baseline to 6 Months [ Time Frame: 6 months ]
    Number of participants who had a decrease in weight from baseline to 6 months of Octreotide or placebo therapy
  • Number of Participants With Decreased BMI Z-score From Baseline to 6 Months [ Time Frame: 6 months ]
    Number of participants with decreased BMI z-score from baseline to 6 months of Octreotide or Placebo therapy
  • Number of Participants With Decreased Skin-fold Measurements From Baseline to 6 Months [ Time Frame: 6 months ]
    Number of participants with decreased skin-fold measurements from baseline to 6 months of Octreotide or Placebo therapy
  • Number of Participants With Decrease in Hunger and Food Intake [ Time Frame: 6 months ]
    Measured by hunger and hyperphagia by questionnaires and parent-reported 72-hour food recall from baseline to 6 months. Multiple questionnaires consisting of a battery of free text answer questions and food diaries are combined in order to make a behavioral assessment of the participants food state of hunger and food intake. There is no defined scale for this assessment. Each participants responses and parent responses are combined.
  • Number of

    Original Primary Outcome:

    • Fasting total ghrelin-measured at months 0-6
    • Hunger and food intake - measurement of hunger and hyperphagia by questionnaires and energy intake by parental-reported 72-hour food recall and by ad-libitum breakfast test meal-measured at months0-6
    • Anthropometric Data - weight, height, BMI, skin-fold measurements - measured at months 0-6


    Current Secondary Outcome:

    • Number of Participants With Decreased Body Composition From Baseline to 6 Months by BOD POD® [ Time Frame: 6 months ]
      Number of participants with decreased body-composition as Measured by BOD POD® body composition tracking system from baseline to 6 months of Octreotide or Placebo therapy
    • Number of Participants With Decreased Body-composition From Baseline to 6 Months by DEXA [ Time Frame: 6 months ]
      Number of participants with decreased body-composition as Measured by Dual Energy X-ray Absorptiometry (DEXA) scan from baseline to 6 months of Octreotide or Placebo therapy


    Original Secondary Outcome:

    • Body-composition - measurement by dual energy e-ray absorptiometry (DEXA), air displacement plethysmography (BOD POD) and bioelectrical impedance analysis (BIA) - measured at months 0, 3, and 6
    • Resting energy expenditure - measured by indirect calorimetry - measured at months 0, 3 and 6
    • Fasting CCK, PYY, glucose, leptin, insulin, adiponectin concentrations - measured at months 0-6
    • Postprandial ghrelin (total and acylated), glucose, insulin, leptin, adiponectin, CCK and PYY concentrations - measured at months 0, 3, and 6


    Information By: Duke University

    Dates:
    Date Received: November 14, 2006
    Date Started: December 2006
    Date Completion:
    Last Updated: June 25, 2014
    Last Verified: June 2014