Effects of exenatide on appetite and ghrelin in Prader-Willi Syndrome

• Research type

  Research Study

• Full title

  Effects of exenatide on appetite and ghrelin levels in patients with Prader-Willi Syndrome

• IRAS ID

  57540

• Sponsor organisation

  University Hospital Aintree

• Eudract number

  2010-023179-25

• Research summary

  Background & why it is important.Prader-Willi Syndrome (PWS) is a rare genetic form of obesity associated with several features, including unappeasable hunger and uncontrolled compulsive eating, leading to obesity from childhood, increased illness and death. Despite some recent advances in understanding the genetic and disease-causing abnormalities in this condition, the reasons for abnormal eating remain unclear and effective treatments are lacking.Ghrelin, the most powerful hunger hormone, is markedly raised in PWS and a possible cause of over-eating. In rodent studies, exendin-4 dramatically reduces fasting ghrelin and decreases food intake. In humans, it significantly reduces food intake and improves glucose and insulin dynamics. Synthetic exendin-4 (Exenatide) is approved for treatment in type 2 diabetes and has consistently helped reduce appetite, with significant and progressive weight loss.What questions will it answer, the study design and what is involved for participants?We propose to undertake a double-blind, placebo-controlled study where a single dose of Exenatide and a single dose of placebo will be given on two separate occasions to 10 adults with PWS and 10 healthy controls with simple obesity matched for age and body mass index to study the effects on ghrelin and other appetite-regulating hormones (by taking blood tests) on fullness, hunger and food intake (by ratings of fullness and hunger and recording food intake). We will also examine hormone expression in fat tissue by obtaining a needle fat biopsy to explore possible links with abnormal body composition in PWS.What are the potential benefits?If differences are seen, exenatide may be a useful treatment of over-eating and obesity in patients with PWS.Who is funding the research and where it will be recruiting?The study is funded by the Foundation of Prader Willi Research and will be conducted at University Hospital Aintree, with recruitment here, from Imperial College London and via the PWS Association (UK) website.

• REC name

  North West - Greater Manchester South Research Ethics Committee

• REC reference

  10/H1003/106

• Date of REC Opinion

  22 Jul 2011

• REC opinion

  Further Information Favourable Opinion