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

This study has been terminated.
(Inadequate recruitment)
Sponsor:
Collaborators:
Novartis
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00399893
First received: November 14, 2006
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention
Prader-Willi Syndrome
Drug: Octreotide
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Number of Participants With Decrease in Fasting Total Ghrelin [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Number of participants with improved Peptide YY (PYY) regulation from baseline to 6 months of Octreotide or Placebo therapy


Secondary Outcome Measures:
  • Number of Participants With Decreased Body Composition From Baseline to 6 Months by BOD POD® [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Enrollment: 5
Study Start Date: December 2006
Study Completion Date: September 2010
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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

Ages Eligible for Study:   5 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00399893

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Novartis
Investigators
Principal Investigator: Andrea M Haqq, MD Duke University
  More Information

Publications:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00399893     History of Changes
Other Study ID Numbers: Pro00005426, Protocol #00005426
Study First Received: November 14, 2006
Results First Received: January 28, 2013
Last Updated: June 25, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Childhood obesity
Prader-Willi Syndrome
Octreotide
Ghrelin
Weight loss
Body composition
Energy expenditure

Additional relevant MeSH terms:
Prader-Willi Syndrome
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Obesity
Overnutrition
Nutrition Disorders
Octreotide
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 21, 2014