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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Drug: Octreotide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Octreotide<br>Octreotide to be administered by subcutaneous injection three times daily while on study | Drug: Octreotide<br>* Octreotide to be administered by subcutaneous injection three times daily<br>* Other names: Sandostatin;|
| Placebo Comparator: Placebo<br>Placebo to be administered by subcutaneous injection three times daily while on study | Drug: Placebo<br>* Placebo to be administered by subcutaneous injection three times daily while on study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Decrease in Fasting Total Ghrelin | Number of participants showing a decrease in Fasting total ghrelin from baseline to 6 months of treatment with Octreotide or placebo | 6 months | 
| Number of Participants With Decrease in Weight From Baseline to 6 Months | Number of participants who had a decrease in weight from baseline to 6 months of Octreotide or placebo therapy | 6 months | 
| Number of Participants With Decreased BMI Z-score From Baseline to 6 Months | Number of participants with decreased BMI z-score from baseline to 6 months of Octreotide or Placebo therapy | 6 months | 
| Number of Participants With Decreased Skin-fold Measurements From Baseline to 6 Months | Number of participants with decreased skin-fold measurements from baseline to 6 months of Octreotide or Placebo therapy | 6 months | 
| Number of Participants With Decrease in Hunger and Food Intake | 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. | 6 months | 
| Number of Participants With Improved Insulin Regulation From Baseline to 6 Months | Number of participants with improved Insulin regulation from baseline to 6 months of Octreotide or Placebo therapy. Insulin regulation was measured by immunochemiluminescent assay. | 6 months | 
| Number of Participants With Improved Adiponectin Regulation From Baseline to 6 Months | Number of participants with improved Adiponectin regulation from baseline to 6 months of Octreotide or Placebo therapy | 6 months | 
| Number of Participants With Improved Leptin Regulation From Baseline to 6 Months | Number of participants with improved Leptin regulation from baseline to 6 months of Octreotide or Placebo therapy | 6 months | 
| Number of Participants With Improved Peptide YY (PYY) Regulation From Baseline to 6 Months | Number of participants with improved Peptide YY (PYY) regulation from baseline to 6 months of Octreotide or Placebo therapy | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Decreased Body Composition From Baseline to 6 Months by BOD POD® | 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 | 6 months | 
| Number of Participants With Decreased Body-composition From Baseline to 6 Months by DEXA | 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 | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Childhood obesity, Prader-Willi Syndrome, Octreotide, Ghrelin, Weight loss, Body composition, Energy expenditure