Ghrelin Suppression by Octreotide in Prader-Willi

Ghrelin Suppression by Sandostatin LAR® Depot (Octreotide Acetate for Injectable Suspension) in Patients With Prader-Willi Syndrome

The purpose of this study is to learn more about how octreotide (Sandostatin LAR® Depot) affects levels of ghrelin, hunger, and body weight in people with Prader-Willi Syndrome.

Study Overview

• Status: Active, not recruiting
• Conditions: Prader Willis Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Octreotide

Detailed Description

After baseline tests, a nurse will administer monthly injections of Sandostatin LAR® or placebo for 6 months. At the end of this initial 6-month treatment period and a 4-month washout period, study subjects will then crossover to receive the alternative therapy (placebo or octreotide) for an additional 6 months. Subjects will be followed for 16 months total at scheduled visits: 0, 2, 6, 10, 12, and 16 months (Table 2).

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• o Diagnosis of PWS confirmed by chromosome analysis (i.e. interstitial deletion of paternally-derived chromosome 15Q, uniparental maternal disomy or other chromosome 15 abnormalities)

  • Age 18 years and older
  • Written informed consent obtained (by subject or guardian) and willingness to comply with the study schedule and procedures
  • Free T4, TSH values in the normal range (with or without thyroxine replacement)
  • Subjects with confirmed hypogonadism who are corrected with adequate doses of sex steroid replacement, will have been treated for at least 6 months prior to entry and have no change in dosages over the study period.
  • Patients with confirmed growth hormone deficiency who are corrected with adequate doses of replacement, will have been treated for at least 6 months prior to entry and have no change in dosages over the study period.

Exclusion Criteria:

• Symptomatic gallstones.
• Smokers.
• Alcohol consumption > 2 drinks per day.
• Exercise > 30 minutes 3 times a week.
• Weight > 500 lbs (exceeds the limit for the BODPOD).
• Active pulmonary infection.
• Sleep disorder.
• Subjects will be excluded if they have clinically significant disease that would have an impact on metabolic outcomes or body composition including diabetes mellitus, chronic inflammatory bowel disease, chronic severe liver or kidney disease, heart disease, cancer, symptomatic gallstones, or neurological disorders
• history of hepatic disease (patients with minimal, i.e., <3Xs the upper limit of normal for LFTs indicative of hepatic steatosis, MAY participate)
• pregnant or lactating
• known hypersensitivity to Sandostatin acetate or other related drug or compound
• subjects who exhibit symptoms indicative of intolerance following the 100 mcg test dose of Sandostatin Injection, SC
• subjects who have previously received Sandostatin® (octreotide)
• subjects who have received other investigational drugs administered or received within 30 days of study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Normal Saline	Drug: Placebo; After the first study visit, subjects will begin monthly treatment with either the study drug or a placebo (an inactive substance), which will be continued for the first six months of the study. For the last six months of the study, subjects will be switched to the opposite treatment. During these study periods participants will return monthly for administration of study medication, physical examination, and blood draw to check liver enzymes.; Other Names: Normal Saline
Active Comparator: Octreotide; They will be admitted to the inpatient unit of the OCTRI for testing six times. During each of these visits, testing will include measuring how well glucose (sugar) is processed, how much energy is burned off as heat, their amount of body fat, levels of the hormone ghrelin, and how much food is eaten at a meal. After the first study visit, subjects will begin monthly treatment with either the study drug or a placebo (an inactive substance), which will be continued for the first six months of the study. For the last six months of the study, subjects will be switched to the opposite treatment. During these study periods participants will return monthly for administration of study medication, physical examination, and blood draw to check liver enzymes.	Drug: Octreotide; They will be admitted to the inpatient unit of the OCTRI for testing six times. During each of these visits, testing will include measuring how well glucose (sugar) is processed, how much energy is burned off as heat, their amount of body fat, levels of the hormone ghrelin, and how much food is eaten at a meal. After the first study visit, subjects will begin monthly treatment with either the study drug or a placebo (an inactive substance), which will be continued for the first six months of the study. For the last six months of the study, subjects will be switched to the opposite treatment. During these study periods participants will return monthly for administration of study medication, physical examination, and blood draw to check liver enzymes.; Other Names: Sandostatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ghrelin levels	Change from baseline to 6 months
Appetite	Change from baseline to 6 months
Body weight	Change from baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Hormone levels	Change from baseline to 6 months
Body composition	Change from baseline to 6 months
Energy expenditure	Change from baseline to 6 months
Glucose metabolism	Change from baseline to 6 months

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Investigators: Principal Investigator: Jonathan Q Purnell, M.D., Oregon Health and Science University; Principal Investigator: Jonathan Q Purnell, M.D., Oregon Health & Sciences University Portland, OR

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: April 13, 2011
• First Submitted That Met QC Criteria: June 4, 2012
• First Posted (Estimate): June 7, 2012

Study Record Updates

• Last Update Posted (Actual): December 16, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: obesity
• 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: eIRB #1265; OCTRI # __910_____ (Other Identifier: Oregon Health and Sciences University)