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

• ClinicalTrials.gov Identifier: NCT00399893
• Recruitment Status: Terminated
• First Posted: November 15, 2006
• Results First Posted: July 24, 2014
• Last Update Posted: July 24, 2014
• Sponsor: Duke University
• Collaborators: National Institutes of Health (NIH); National Center for Research Resources (NCRR); Novartis
• Information provided by (Responsible Party): Duke University

Tracking Information

• First Submitted Date: November 14, 2006
• First Posted Date: November 15, 2006
• Results First Submitted Date: January 28, 2013
• Results First Posted Date: July 24, 2014
• Last Update Posted Date: July 24, 2014
• Study Start Date: December 2006
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 25, 2014)

• 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 Participants With Improved Insulin Regulation From Baseline to 6 Months [ Time Frame: 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.
• Number of Participants With Improved Adiponectin Regulation From Baseline to 6 Months [ Time Frame: 6 months ]
  Number of participants with improved Adiponectin regulation from baseline to 6 months of Octreotide or Placebo therapy
• Number of Participants With Improved Leptin Regulation From Baseline to 6 Months [ Time Frame: 6 months ]
  Number of participants with improved Leptin regulation from baseline to 6 months of Octreotide or Placebo therapy
• Number of Participants With Improved Peptide YY (PYY) Regulation From Baseline to 6 Months [ Time Frame: 6 months ]
  Number of participants with improved Peptide YY (PYY) regulation from baseline to 6 months of Octreotide or Placebo therapy

Original Primary Outcome Measures (submitted: November 14, 2006)

• 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 Measures (submitted: June 25, 2014)

• 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 Measures (submitted: November 14, 2006)

• 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Prader-Willi Syndrome

Intervention

• Drug: Octreotide
  Octreotide to be administered by subcutaneous injection three times daily
  Other Name: Sandostatin
• Drug: Placebo
  Placebo to be administered by subcutaneous injection three times daily while on study

Study Arms

• Experimental: Octreotide
  Octreotide to be administered by subcutaneous injection three times daily while on study
  Intervention: Drug: Octreotide
• Placebo Comparator: Placebo
  Placebo to be administered by subcutaneous injection three times daily while on study
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 25, 2014): 5
• Original Enrollment (submitted: November 14, 2006): 26
• Actual Study Completion Date: September 2010
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00399893
• Other Study ID Numbers: Pro00005426; Protocol #00005426 ( Other Grant/Funding Number: NIH:1K23-RR021979, GCRC M01-RR-30 (NCRR) )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Duke University
• Original Responsible Party: Not Provided
• Current Study Sponsor: Duke University
• Original Study Sponsor: Same as current

Collaborators

• National Institutes of Health (NIH)
• National Center for Research Resources (NCRR)
• Novartis

Investigators

• Principal Investigator: Andrea M Haqq, MD; Duke University

• PRS Account: Duke University
• Verification Date: June 2014