NCT02971631

Gastrectomy, Eating Behaviour and GLP-1

Completed NA Results posted Last updated 29 August 2019

What this trial tests

NA trial testing Exendin 9-39 in Gastric Cancer in 5 participants. Completed in 16 September 2018.

Timeline

10 August 2017

Primary endpoint
16 September 2018

16 September 2018

Quick facts

Lead sponsor	Cambridge University Hospitals NHS Foundation Trust
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	quadruple
Primary purpose	basic science
Enrollment	5
Start date	10 August 2017
Primary completion	16 September 2018
Estimated completion	16 September 2018
Sites	1 location across United Kingdom

Drugs / interventions tested

• Exendin 9-39 — full drug profile →
• Placebo

Conditions studied

• Gastric Cancer — all drugs for Gastric Cancer →
• Dumping Syndrome — all drugs for Dumping Syndrome →

Sponsor

Cambridge University Hospitals NHS Foundation Trust

Who can join

Adults 18 to 100, any sex, with Gastric Cancer or Dumping Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Nadir Blood Glucose Primary · 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.

Group	Value	95% CI
Placebo	3	± 0.3
Exendin	4.4	± 0.3

Total Insulin Secretion Secondary · Samples collected at 0, 15, 30, 45 and 60 minutes post oral glucose tolerance test.

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.

Group	Value	95% CI
Placebo	41000	± 10400
Exendin	14500	± 2600

Eating Rate During ad Libitum Meal Secondary · 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.

Group	Value	95% CI
Placebo	0.62	± 0.12
Exendin	0.66	± 0.07

Altered Food Attention. Secondary · 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).

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).

Time 0

Group	Value	95% CI
Placebo	17.9	± 8.6
Exendin	11.1	± 7.1

Post OGTT

Group	Value	95% CI
Placebo	18.2	± 4.1
Exendin	12.0	± 9.0

Pre-meal

Group	Value	95% CI
Placebo	24.8	± 10.8
Exendin	17.9	± 8.9

Post-meal

Group	Value	95% CI
Placebo	25.7	± 10.8
Exendin	10.7	± 3.0

Altered Food Motivation Secondary · 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.

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).

T0 / Baseline

Group	Value	95% CI
Placebo	508	± 182
Exendin	219	± 69

Post-OGTT

Group	Value	95% CI
Placebo	139	± 63
Exendin	274	± 56

Pre-meal

Group	Value	95% CI
Placebo	328	± 82
Exendin	339	± 116

Post-meal

Group	Value	95% CI
Placebo	207	± 82
Exendin	227	± 116

Number of Participants With Infusion Related Adverse Events as Assessed by CTCAE v4 Secondary · 24 hours from onset of infusion.

Group	Value	95% CI
Placebo	0
Exendin	0

Total Meal Consumption Secondary · 150-210 minutes during infusion of Exendin 9-39 or placebo

Total consumption amount of a standard meal during study intervention, measured in grams using a universal eating monitor.

Group	Value	95% CI
Placebo	422	± 45
Exendin	434	± 162

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery.
   Larraufie P, Roberts GP, McGavigan AK, Kay RG, et al · · 2019 · cited 122× · PMID 30726726 · DOI 10.1016/j.celrep.2019.01.047