Gastrectomy, Eating Behaviour and GLP-1

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

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer; Dumping Syndrome
• Intervention / Treatment: Other: Placebo; Other: Exendin 9-39

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Cambridge University Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • At least 3 months post completion of treatment for gastric cancer, or prophylactic gastrectomy

  • Aged at least 18 years
  • Able to tolerate an oral glucose tolerance test
  • Able to understand and retain all information regarding the study and give informed consent.
  • Willing to receive an infusion of human albumin solution

Exclusion Criteria:

• • Have a diagnosis of diabetes

  • Have a history of untreated anaemia in the last 3 months
  • Be aged under 18 years
  • Have active gastric cancer
  • Be pregnant or attempting to conceive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Infusion of 1% human albumin in normal saline.	Other: Placebo; Infusion of 1% human albumin in normal saline
EXPERIMENTAL: Exendin; Infusion of Exendin 9-39 in 1% human albumin in normal saline	Other: Exendin 9-39; Complete blockade of action of endogenous GLP-1 by Exendin 9-39. Defined as a physiological study, not a clinical trial as such (as advised by the UK MHRA).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nadir Blood Glucose	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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Insulin Secretion	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.	Samples collected at 0, 15, 30, 45 and 60 minutes post oral glucose tolerance test.
Eating Rate During ad Libitum Meal	As measured by universal eating monitor, total weight of a standardised meal consumed over a measured time in grams per minute.	150-210 minutes during infusion of Exendin 9-39 or placebo.
Decreased Hunger and Satiety Ratings During and After ad Libitum Meal	Will be measured on visual analogue scale and reported as a score out of 100. Higher value indicated more hunger and more satiety.	150-240 minutes during infusion of Exendin 9-39 or placebo and for 4 hours post-cessation of infusion.
Altered Food Attention.	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. Measure is of difference in response time when visual cue is colocated with a food related image vs a non-food related image, indicating degree of bias in attention to food images. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).	0-240 minutes during infusion of Exendin 9-39 or placebo, assessed on four occasions (baseline or T0, post-OGTT, pre-meal, post-meal) using a validated dot-probe visual response tool and reported in response time (milliseconds).
Altered Food Motivation	Participant motivation to view particular food based cues is assessed by grip strength exerted to maintain those cues. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).	0-240 minutes during infusion of Exendin 9-39 or placebo (baseline or T0, post-OGTT, pre-m, 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.
Number of Participants With Infusion Related Adverse Events as Assessed by CTCAE v4		24 hours from onset of infusion.
Total Meal Consumption	Total consumption amount of a standard meal during study intervention, measured in grams using a universal eating monitor.	150-210 minutes during infusion of Exendin 9-39 or placebo

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Investigators: Principal Investigator: Geoffrey Roberts, MA BM BCh, University of Cambridge

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 10, 2017
• Primary Completion (ACTUAL): September 16, 2018
• Study Completion (ACTUAL): September 16, 2018

Study Registration Dates

• First Submitted: November 17, 2016
• First Submitted That Met QC Criteria: November 20, 2016
• First Posted (ESTIMATE): November 23, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 29, 2019
• Last Update Submitted That Met QC Criteria: August 27, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Insulin; GLP-1; Gastrectomy; Dumping syndrome
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Postoperative Complications; Gastrointestinal Diseases; Stomach Diseases; Postgastrectomy Syndromes; Dumping Syndrome
• Other Study ID Numbers: A094265; 218762 (OTHER: IRAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No