None listed
Conditions
Brief summary
Prader-Willi syndrome (PWS) is a rare genetic disorder that causes individuals with the disease to have an insatiable appetite, which often leads to the development of morbid obesity. The only way that this appetite can be controlled is through constant vigilance, behavioural restraints and environmental modifications; there is currently no pharmacological treatment for excessive appetite in PWS. A single injection of exenatide, a GLP-1 hormone agonist, has been shown to increase feelings of fullness after a meal in adults with PWS. The effects of the long term administration of a GLP-1 agonist on appetite and weight management in PWS, however, have not been studied. The proposed study aims to redress this by assessing changes in gastric emptying rate, fullness, hunger, food-related behaviours, appetite hormones, cognitive function and body weight in a cohort of 20 adults with PWS treated for 12 weeks with the GLP-1 agonist Bydureon. Study participants will undergo a meal study prior to beginning Bydureon treatment to assess their response of hormones and appetite to food intake. As there have been some studies demonstrating that Bydureon slows gastric emptying, participants’ gastric emptying rate will be also be assessed by scintigraphy so that changes in gastric motility can be monitored for tolerance, with a normal gastric emptying range established from 10 lean control individuals and 10 obese control individuals. If PWS particpants’ gastric emptying rate falls within the normal range, they will begin a 12-week Bydureon treatment period with weekly injections of the drug. After 4 weeks of Bydureon treatment, gastric emptying rate will be measured again. If it has slowed below the normal range, treatment will be discontinued. Otherwise, treatment will be continued up to 12 weeks, after which PWS participants will undergo a further meal/scintigraphy study to determine the effect that Bydureon treatment has had on appetite, weight, behaviour and cognitive function. Body weight will be measured again 12 weeks after completion of the treatment period.
Interventions
Administration of exenatide extended realease ( Bydureon) 2mg subcutaneous injection once weekly on adults with Prader-Willi Syndrome for 12 weeks. Adherence will be monitored by return of empty or unused injection pens by the patients or carers of patients.
Gastric emptying assessment is performed using the gold standard gastric scintigraphy.
Participants will fast from 10:00pm the night before the study. On the day of the study, anthropometric measurements will be taken and fasting blood samp
Administration of exenatide extended realease ( Bydureon) 2mg subcutaneous injection once weekly on adults with Prader-Willi Syndrome for 12 weeks. Adherence will be monitored by return of empty or unused injection pens by the patients or carers of patients. Gastric emptying assessment is performed using the gold standard gastric scintigraphy. Participants will fast from 10:00pm the night before the study. On the day of the study, anthropometric measurements will be taken and fasting blood samples will be drawn. In St Vincent Hospital’s nuclear medicine unit, a cannula will be placed in participants’ arms and they will be given a meal (scrambled eggs with potato, ricotta and cheese) labelled with 99mTc Calcium Phytate Colloid and asked to eat it within 10 minutes. Participants will then lie supine during four 10-minute scans: immediately after eating the meal and at 1 hour, 2 hours and 4 hours postprandial. Blood samples will be collected prior to meal ingestion and immediately before each scanning time point. Plasma and serum will be obtained from blood samples collected during the study by centrifugation and stored at -80°C until being analysed for levels of glucose, insulin, gut hormones and lipids. Appetite will be assessed using hunger and fullness visual analogue scales before and hourly after the meal. After completion of the scintigraphy study, participants will have a DXA scan to quantify lean mass and fat mass.
Sponsors
Garvan Institute of Medical Research
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
PWS group: genetic diagnosis of PWS BMI-matched group( instead of Obese group): healthy; any obesity-related comorbidities must be treated, BMI -matched to PWS cohort. Lean group: health; BMI <25
Exclusion criteria
PWS: Uncontrolled access to food in current living situation; history of psychological illness within previous 12 months; pregnant women. Obese: unstable body weight within previous 3 months (+/- 2kg or greater); pregnant women. Lean: unstable body weight within previous 3 months (+/- 2kg or greater); pregnant women.
Outcome results
None listed