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. Sample size calculations: Statistical considerations 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
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
370723-ENGAGE_Protocol_v2.docx