Clinical trial NCT00399893: Octreotide Therapy in Children and Young Adults With Prader-Willi Syndrome (PWS)
Official title: Investigation of the Developmental, Nutritional and Hormonal Regulation of Ghrelin in Children and Young Adults With Prader-Willi Syndrome (PWS): Octreotide Intervention Sub-study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Prader-Willi Syndrome
Keywords: Childhood obesity
Prader-Willi Syndrome
Octreotide
Ghrelin
Weight loss
Body composition
Energy expenditure
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Center for Research Resources (NCRR)
name: Novartis
First posted: 2006-11-15
Enrollment: 5
Sex: ALL
Minimum age (years): 5
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 description: 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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of PWS confirmed by chromosome analysis
* Ages 5 years to 21 years
* BMI for age ≥ (greater-than or equal to)85th percentile
* Written informed consent and assent obtained and willingness to comply with the study schedule and procedures
* Free T4, Thyroid stimulating hormone (TSH) values in the normal range (either endogenous or with thyroxine replacement)

Exclusion Criteria:

* Patients with any other clinically significant disease that would have an impact on body composition, including diabetes mellitus, chronic inflammatory bowel disease, chronic severe liver or kidney disease or neurologic disorders
* Concomitant use of an investigational drug or Octreotide in the past year
* Use of steroids for longer than 7 days within the past 30 days

Primary outcomes:
measure: Number of Participants With Decrease in Fasting Total Ghrelin
timeFrame: 6 months
measure: Number of Participants With Decrease in Weight From Baseline to 6 Months
timeFrame: 6 months
measure: Number of Participants With Decreased BMI Z-score From Baseline to 6 Months
timeFrame: 6 months
measure: Number of Participants With Decreased Skin-fold Measurements From Baseline to 6 Months
timeFrame: 6 months
measure: Number of Participants With Decrease in Hunger and Food Intake
timeFrame: 6 months
measure: Number of Participants With Improved Insulin Regulation From Baseline to 6 Months
timeFrame: 6 months
measure: Number of Participants With Improved Adiponectin Regulation From Baseline to 6 Months
timeFrame: 6 months
measure: Number of Participants With Improved Leptin Regulation From Baseline to 6 Months
timeFrame: 6 months
measure: Number of Participants With Improved Peptide YY (PYY) Regulation From Baseline to 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Number of Participants With Decreased Body Composition From Baseline to 6 Months by BOD POD®
timeFrame: 6 months
measure: Number of Participants With Decreased Body-composition From Baseline to 6 Months by DEXA
timeFrame: 6 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Andrea M Haqq, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haqq AM, Stadler DD, Rosenfeld RG, Pratt KL, Weigle DS, Frayo RS, LaFranchi SH, Cummings DE, Purnell JQ. Circulating ghrelin levels are suppressed by meals and octreotide therapy in children with Prader-Willi syndrome. J Clin Endocrinol Metab. 2003 Aug;88(8):3573-6. doi: 10.1210/jc.2003-030205.