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

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

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).

Study Overview

• Status: Terminated
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Drug: Octreotide; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Octreotide; Octreotide to be administered by subcutaneous injection three times daily while on study	Drug: Octreotide; Octreotide to be administered by subcutaneous injection three times daily; Other Names: Sandostatin
Placebo Comparator: Placebo; Placebo to be administered by subcutaneous injection three times daily while on study	Drug: Placebo; Placebo to be administered by subcutaneous injection three times daily while on study

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Novartis; National Institutes of Health (NIH); National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Andrea M Haqq, MD, Duke University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: November 14, 2006
• First Submitted That Met QC Criteria: November 14, 2006
• First Posted (Estimate): November 15, 2006

Study Record Updates

• Last Update Posted (Estimate): July 24, 2014
• Last Update Submitted That Met QC Criteria: June 25, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Energy expenditure; Weight loss; Body composition; Childhood obesity; Octreotide; Prader-Willi Syndrome; Ghrelin
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: Pro00005426; Protocol #00005426 (Other Grant/Funding Number: NIH:1K23-RR021979, GCRC M01-RR-30 (NCRR))