Protocol version 2 Objectives Primary: To determine the gastrointestinal safety of exenatide extended release (exenatide ER) treatment in PWS by assessing its effects on gastric emptying. Secondary: To assess the effects of weekly administration of exenatide ER on appetite, body weight, behaviour and cognition in PWS. Study design Prospective study Planned sample size PWS group: n=20 Obese group: n=10 Lean group: n=10 Total: n=40 Selection criteria PWS group: age 18-65; genetic diagnosis of PWS Obese group: age 18-65; healthy; BMI>30 Lean group: age 18-65; healthy; BMI<25 Study procedures Anthropometric measurements, dual-energy X-ray absorptiometry, gastric scintigraphy, food and behaviour questionnaire, tablet-based cognitive function tests, blood sampling. Statistical considerations Sample size calculations: To detect a difference in 4-hour gastric retention between groups with statistical power 1- β>0.85, we will require 8 individuals in each group. Allowing for a drop-out rate of 20%, this requires 10 participants for each of the control groups. As we anticipate that some PWS participants may not be eligible to enter the treatment arm of the study, we aim to recruit 20 individuals in the PWS group initially. Analysis plan: Baseline differences between groups in gastric emptying rate and anthropometric measurements will be analysed by one-way ANOVA. Changes in body weight, waist and hip circumference and cognitive function test scores in the PWS group throughout the course of the study will be analysed by repeated measures ANOVA. Study duration 16 months 1. BACKGROUND 6 1.1. DISEASE BACKGROUND 6 1.2. RATIONALE FOR PERFORMING THE STUDY 6 2. STUDY OBJECTIVES 6 2.1. PRIMARY OBJECTIVE 6 2.2. SECONDARY OBJECTIVES 6 3. STUDY DESIGN 7 3.1. DESIGN 7
PWS: Age range 18-65; genetically confirmed PWS Obese: Age range 18-65; BMI>30 Lean: Age range 18-65; BMI<25 4.2 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. 5. STUDY OUTLINE 5.1 STUDY FLOW CHART (FIGURE 1) 5.2 INVESTIGATION PLAN Table 1: Procedures performed at the Garvan Clinical Research Facility during the study. Study visits: Lean and obese control subjects Visit 1 – Screening and enrolment: After initial contact by phone in response to newspaper advertisement, control subjects will undergo screening at the Garvan Institute Clinical Research Facility. A clinical assessment will be performed and, if suitable for the study and willing to participate, subjects will give informed consent and enter the study. Visit 2 – Gastric scintigraphy study: Participants will fast from 10:00pm the night before the study and, upon arrival at the Garvan Institute Clinical Research Facility at 8:00am on the study day, height, weight and waist and hip circumference will be measured, and fasting blood samples will be drawn. Participants will be taken across the road to St Vincent’s Hospital where they will undergo a gastric scintigraphy study, which involves insertion of an intravenous cannula, eating a breakfast and having blood samples collected at regular intervals. After completion of the scintigraphy study, participants will have a DXA scan at St Vincent’s Hospital to quantify lean mass and fat mass. labelled