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| ID | Type | Description | Link |
|---|---|---|---|
| 218762 | Other Identifier | IRAS |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Infusion of 1% human albumin in normal saline. |
|
| Exendin | Experimental | Infusion of Exendin 9-39 in 1% human albumin in normal saline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
|
| 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. |
| 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. |
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Inclusion Criteria:
• At least 3 months post completion of treatment for gastric cancer, or prophylactic gastrectomy
Exclusion Criteria:
• Have a diagnosis of diabetes
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| Name | Affiliation | Role |
|---|---|---|
| Geoffrey Roberts, MA BM BCh | University of Cambridge | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cambridge University Hospitals NHS Foundation Trust | Cambridge | Cambridgeshire | CB2 0QQ | United Kingdom |
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Five participants recruited from Hereditary Diffuse Gastric Cancer patient population
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention - One Day |
| |||||||||||||
| Second Intervention - One Day |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants were randomised to reveal both interventions, so baseline characteristics are reported for the whole study population. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Crossover study - analysis by paired T test | Posted | Mean | Standard Error | mmol/l | 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. |
|
1 week.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Infusion of 1% human albumin in normal saline. Placebo: Infusion of 1% human albumin in normal saline |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mr Geoffrey Roberts | University of Cambridge | 01223767176 | geoffroberts@cantab.net |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 24, 2016 | Sep 17, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D013274 | Stomach Neoplasms |
| D004377 | Dumping Syndrome |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C083773 | exendin (9-39) |
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| Placebo | Other | Infusion of 1% human albumin in normal saline |
|
| 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 |
| NOT COMPLETED |
|
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | 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.
|
|
|
| Secondary | 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. | Posted | Mean | Standard Error | pmol*minute/l | Samples collected at 0, 15, 30, 45 and 60 minutes post oral glucose tolerance test. |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Error | grams/minute | 150-210 minutes during infusion of Exendin 9-39 or placebo. |
|
|
|
|
| Secondary | 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. | 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. | Posted | 150-240 minutes during infusion of Exendin 9-39 or placebo and for 4 hours post-cessation of infusion. |
|
|
| Secondary | 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). | Posted | Mean | Standard Error | milliseconds | 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). |
|
|
|
|
| Secondary | 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). | Posted | Mean | Standard Error | Newton seconds | 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. |
|
|
|
|
| Secondary | Number of Participants With Infusion Related Adverse Events as Assessed by CTCAE v4 | Posted | Number | participants | 24 hours from onset of infusion. |
|
|
|
|
| Secondary | Total Meal Consumption | Total consumption amount of a standard meal during study intervention, measured in grams using a universal eating monitor. | Posted | Mean | Standard Error | grams | 150-210 minutes during infusion of Exendin 9-39 or placebo |
|
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 0 |
| 5 |
| EG001 | Exendin | 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. | 0 | 5 | 0 | 5 | 0 | 5 |
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| D004066 |
| Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |
| D011178 | Postgastrectomy Syndromes |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Pre-meal |
|
| Post-meal |
|
Paired analysis |
| 0.58 |
| Superiority |
| Pre-meal | t-test, 2 sided | Paired analysis | 0.39 | Superiority |
| Post-meal | t-test, 2 sided | Paired analysis | 0.20 | Superiority |
| Pre-meal |
|
| Post-meal |
|
| 0.06 |
Paired analysis |
| Superiority |
| Pre-meal | t-test, 2 sided | Paired analysis | 0.95 | Superiority |
| Post-meal | t-test, 2 sided | Paired analysis | 0.88 | Superiority |