Trial Outcomes & Findings for Gastrectomy, Eating Behaviour and GLP-1 (NCT NCT02971631)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

5 participants

Primary outcome timeframe

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.

Results posted on

2019-08-29

Participant Flow

Five participants recruited from Hereditary Diffuse Gastric Cancer patient population

Participant milestones

Participant milestones
Measure	Placebo Then Exendin Infusion of 1% human albumin in normal saline on day one of study. Infusion of Exendin 9-39 in 1% human albumin in normal saline on day two of study (bolus of 7500pmol/kg followed by infusion of 500pmol/kg/minute for 4 hours).	Exendin Then Placebo Infusion of Exendin 9-39 in 1% human albumin in normal saline on day one of study (bolus of 7500pmol/kg followed by infusion of 500pmol/kg/minute for 4 hours). Infusion of 1% human albumin in normal saline on day two of study.
First Intervention - One Day STARTED	3	2
First Intervention - One Day COMPLETED	3	2
First Intervention - One Day NOT COMPLETED	0	0
Second Intervention - One Day STARTED	3	2
Second Intervention - One Day COMPLETED	3	2
Second Intervention - One Day NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=5 Participants All participants were randomised to reveal both interventions, so baseline characteristics are reported for the whole study population.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Region of Enrollment United Kingdom	5 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: Crossover study - analysis by paired T test

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.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Infusion of 1% human albumin in normal saline. Placebo: Infusion of 1% human albumin in normal saline	Exendin n=5 Participants Infusion of Exendin 9-39 in 1% human albumin in normal saline Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.
Nadir Blood Glucose	3 mmol/l Standard Error 0.3	4.4 mmol/l Standard Error 0.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Infusion of 1% human albumin in normal saline. Placebo: Infusion of 1% human albumin in normal saline	Exendin n=5 Participants Infusion of Exendin 9-39 in 1% human albumin in normal saline Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.
Total Insulin Secretion	41000 pmol*minute/l Standard Error 10400	14500 pmol*minute/l Standard Error 2600

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Infusion of 1% human albumin in normal saline. Placebo: Infusion of 1% human albumin in normal saline	Exendin n=5 Participants Infusion of Exendin 9-39 in 1% human albumin in normal saline Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.
Eating Rate During ad Libitum Meal	0.62 grams/minute Standard Error 0.12	0.66 grams/minute Standard Error 0.07

SECONDARY outcome

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

Population: Unfortunately it proved impossible to collect data on hunger and fullness during the ad libitum meal, due to the cognitive effects of the gastrectomy which all of this group had undergone, meaning participants were unwilling to accurately record these sensations while eating. This data is therefore meaningless and was not analysed.

Will be measured on visual analogue scale and reported as a score out of 100. Higher value indicated more hunger and more satiety.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Infusion of 1% human albumin in normal saline. Placebo: Infusion of 1% human albumin in normal saline	Exendin n=5 Participants Infusion of Exendin 9-39 in 1% human albumin in normal saline Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.
Altered Food Attention. Time 0	17.9 milliseconds Standard Error 8.6	11.1 milliseconds Standard Error 7.1
Altered Food Attention. Post OGTT	18.2 milliseconds Standard Error 4.1	12.0 milliseconds Standard Error 9.0
Altered Food Attention. Pre-meal	24.8 milliseconds Standard Error 10.8	17.9 milliseconds Standard Error 8.9
Altered Food Attention. Post-meal	25.7 milliseconds Standard Error 10.8	10.7 milliseconds Standard Error 3.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Infusion of 1% human albumin in normal saline. Placebo: Infusion of 1% human albumin in normal saline	Exendin n=5 Participants Infusion of Exendin 9-39 in 1% human albumin in normal saline Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.
Altered Food Motivation T0 / Baseline	508 Newton seconds Standard Error 182	219 Newton seconds Standard Error 69
Altered Food Motivation Post-OGTT	139 Newton seconds Standard Error 63	274 Newton seconds Standard Error 56
Altered Food Motivation Pre-meal	328 Newton seconds Standard Error 82	339 Newton seconds Standard Error 116
Altered Food Motivation Post-meal	207 Newton seconds Standard Error 82	227 Newton seconds Standard Error 116

SECONDARY outcome

Timeframe: 24 hours from onset of infusion.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Infusion of 1% human albumin in normal saline. Placebo: Infusion of 1% human albumin in normal saline	Exendin n=5 Participants Infusion of Exendin 9-39 in 1% human albumin in normal saline Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.
Number of Participants With Infusion Related Adverse Events as Assessed by CTCAE v4	0 participants	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Infusion of 1% human albumin in normal saline. Placebo: Infusion of 1% human albumin in normal saline	Exendin n=5 Participants Infusion of Exendin 9-39 in 1% human albumin in normal saline Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.
Total Meal Consumption	422 grams Standard Error 45	434 grams Standard Error 162

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Exendin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Mr Geoffrey Roberts

University of Cambridge

Phone: 01223767176

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place