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October 3, 2016
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October 11, 2016
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Webpage:http://www.ucd.ie/conway/research/researchers/conwayfellowsa-z/professorcarelleroux/

Research Field
  • physiology and non-communicable disease
My WorkThe successful research group lead by Professor Carel le Roux and Dr Neil Docherty is focused on translational research to address major questions that may unlock novel treatments for chronic diseases associated with obesity and diabetes. The group has published numerous high impact papers over the years that have changed clinical management of patients. In particular, the translational research on the understanding of the physiological role and pathological changes in appetite control and the impact of bariatric surgery on diabetes have been widely acknowledged.

Working within the Diabetes Complications Research Centre situated in the Conway Institute the focus have been on the increased mortality and morbidity associated with obesity and diabetes. A better mechanistic understanding of how the "gut talks to the brain" will allow safer and more effective treatments to be used in future. To this end the role of gut hormones, bile acids and changes in food preference are areas of present interest. The impact of intentional weight loss as a potential innovative treatment for some obesity driven cancers and the impact of unintentional weight loss on upper gastrointestinal cancer have opened up exciting collaborations with other multidisciplinary groups.

References
N Engl J Med.2015;373(1):11-22.
Lancet.2015;386(9997):936-7.
Cell Metab.2015;22(2):228-38.
Lancet.2012;379(9833):2300-11
N Engl J Med.2003;349(10):941-8.
Outline of Potential Research projectsWeight loss presents a significant and unmet clinical challenge for long-term oesophageal cancer survivors. Our pilot data demonstrate exaggerated post-prandial satiety gut hormone responses after oesophagectomy and we propose that pharmacologic attenuation of this process may be of therapeutic utility. We hypothesise that exaggerated post-prandial satiety gut hormone responses post-oesophagectomy result in reduced appetitive drive and unintentional weight loss. Consequently, pharmacologic attenuation of this response may result in increased food intake and hence body weight. Together with the world renowned group of Prof John Reynolds at Trinity College Dublin we will address the following important aims.

Aim 1: Post-prandial gut hormone secretion will be prospectively characterized among thirty patients undergoing oesophagectomy.

Aim 2: To determine the role of gut hormones as mediators of appetitive drive after oesophagectomy, we will conduct a randomised, double-blind, placebo-controlled crossover study using a validated behavioural paradigm. Changes in appetitive drive will be compared following administration of octreotide among post-oesophagectomy subjects and matched controls.

Aim 3: To determine the role of gut hormones as mediators of early satiety and food intake post-oesophagectomy, a randomised, double-blind, placebo controlled, crossover study of the effect of single dose octreotide on ad libitum calorie consumption will then be conducted.

Aim 4: We will conduct a randomised, double-blind, placebo-controlled, parallel-group study to assess the effect of octreotide therapy on body weight among disease-free post-oesophagectomy patients with persistent weight loss. Subjects¿ weight, micronutrient levels, body composition, ad libitum calorie intake and quality of life will be assessed at the start of the study, after four weeks of intervention and after a four week run-out period. In addition, treatment adherence and adverse events will be documented to determine the feasibility and safety of octreotide therapy in this cohort.