Gastrectomy, Eating Behaviour and GLP-1

NCT02971631 | Completed Results

• 2 other identifiers: A094265218762
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastric Cancer; Dumping Syndrome

Keywords

Dumping syndrome; Gastrectomy; GLP-1; Insulin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Total Insulin Secretion

  Samples collected at 0, 15, 30, 45 and 60 minutes post oral glucose tolerance test.

• Eating Rate During ad Libitum Meal

  150-210 minutes during infusion of Exendin 9-39 or placebo.

• Decreased Hunger and Satiety Ratings During and After ad Libitum Meal

  150-240 minutes during infusion of Exendin 9-39 or placebo and for 4 hours post-cessation of infusion.

• Altered Food Attention.

  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

  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.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Infusion of 1% human albumin in normal saline.

Other: Placebo

Exendin

EXPERIMENTAL

Infusion of Exendin 9-39 in 1% human albumin in normal saline

Other: Exendin 9-39

Interventions

Exendin 9-39 OTHER

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).

Exendin

Placebo OTHER

Infusion of 1% human albumin in normal saline

Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead

Study Sites (1)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

MeSH Terms

Conditions

Stomach Neoplasms; Dumping Syndrome; Insulin Resistance

Interventions

exendin (9-39)

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Postgastrectomy Syndromes; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Mr Geoffrey Roberts
• Organization: University of Cambridge

geoffroberts@cantab.net

01223767176

Study Officials

• Geoffrey Roberts, MA BM BCh

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Research Associate

Study Record Dates

• First Submitted: November 17, 2016
• First Posted: November 23, 2016
• Study Start: August 10, 2017
• Primary Completion: September 16, 2018
• Study Completion: September 16, 2018
• Last Updated: August 29, 2019
• Results First Posted: August 29, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)