Clinical Trial: Gastrectomy, Eating Behaviour and GLP-1

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: The Effect of Glucagon Like Peptide-1 (GLP-1) on Glycaemic Profile and Eating Behaviour Following Gastrectomy

Brief Summary:

Patients who have undergone gastrectomy (removal of the stomach) to treat or prevent cancer are known to have a significantly reduced quality of life. To date, there is very little information on the physiological causes of this. The investigators suspect that overproduction of a hormone (chemical) called glucagon like peptide-1 (GLP-1) released by the lining of the gut may play a role in the reduced appetite, weight loss and low blood sugar symptoms seen in this group. To investigate this, the investigators will study the response of 16 patients who have previously had a gastrectomy to a glucose drink, and a meal, while receiving an infusion of a specific blocker of GLP-1 or placebo. The investigators will examine the levels of sugar and associated hormones in the blood, food consumption and food reward behaviour using standard tools.

Participants will be invited to attend the Clinical Research Facility at Addenbrooke's Hospital for a screening visit, and two whole day study visits. The study has been designed to assess the role of overproduction of GLP-1 by completely blocking its actions, rather than assess the use of the blocking compound as a medication, and is therefore regarded as a physiological study, not a clinical trial.

The goal of this study is to demonstrate the magnitude of effect of GLP-1 on blood sugar and appetite derangement in patients who have had a gastrectomy. This will guide future work on the development of novel treatment paradigms for the post-gastrectomy patient group.


Detailed Summary:
Sponsor: Cambridge University Hospitals NHS Foundation Trust

Current Primary Outcome: Nadir blood glucose [ Time Frame: As assessed during a 50g glucose tolerance test while receiving infusion of GLP-1 antagonist. At time 30-120 minutes of infusion of Exendin 9-39. ]

Lowest blood sugar reading during an oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Reduced total insulin secretion [ Time Frame: 30-90 minutes during infusion of Exendin 9-39 or placebo. ]
    60 minute incremental area under the curve (i.e. total) insulin secretion during 50g oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.
  • Eating rate and total food intake during ad libitum meal [ Time Frame: 150-210 minutes during infusion of Exendin 9-39 or placebo. ]
    As measured by universal eating monitor, total weight of a standardised meal consumed over a measured time in grams per minute.
  • Decreased hunger and satiety ratings during and after ad libitum meal [ Time Frame: 150-240 minutes during infusion of Exendin 9-39 or placebo and for 4 hours post-cessation of infusion. ]
    Will be measured on visual analogue scale and reported as a score out of 100.
  • Altered food attention. [ Time Frame: 0-240 minutes during infusion of Exendin 9-39 or placebo, assessed on four occasions using a validated dot-probe visual response tool and reported in response time (milliseconds). ]
    Food motivation can be measured by response rates to visual cues while being distracted by food related images. Will be measured with and without GLP-1 blockade to investigate effects of GLP-1 on food attention behaviour.
  • Altered food motivation [ Time Frame: 0-240 minutes during infusion of Exendin 9-39 or placebo, assessed on four occasions using a validated grip strength surrogate of food motivation and measured as the area under the curve of a grip force monitoring curve. ]
    Participant motivation to view particular food based cues is assessed by grip strength exerted to maintain those cues.
  • Number of participants with infusion related adverse events as assessed by CTCAE v4 [ Time Frame: 24 hours from onset of infusion. ]


Original Secondary Outcome: Same as current

Information By: Cambridge University Hospitals NHS Foundation Trust

Dates:
Date Received: November 17, 2016
Date Started: January 2017
Date Completion:
Last Updated: November 20, 2016
Last Verified: November 2016