Post-Prandial Carbohydrate Metabolism in Individuals With and Without Post-Bariatric Surgery Hypoglycemia (PBH)
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-70
SponsorJoslin Diabetes Center
About this trial
In this study, the investigators will determine (a) whether metabolism (secretion and turnover) of glucagon is altered in patients with PBH, (b) whether this is affected by a meal, (c) whether PBH affects the ability of the body to produce glucose (endogenous glucose production), and (d) whether PBH affects the amount of glycogen in the liver (storage form of glucose) when fasting and after a meal. The investigators will determine the effect of glucagon to raise glucose levels after a meal. To answer these questions, participants will receive an infusion of a stable (nonradioactive) isotope of glucose and glucagon, and a meal containing a stable isotope of glucose. Glycogen will be measured by magnetic resonance imaging (MRI) of the liver before and after the meal. This information will be used to develop computer models for the glucagon pump system.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age 18-70 years of age, inclusive, at screening.
Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits.
Males or females at least 2 years following Roux-en-Y gastric bypass (RYGB)
For patients recruited to PBH group: diagnosed with ongoing PBH, with documented episodes of hypoglycemia, and history of fulfillment of Whipple's triad.
Disqualifiers
Documented hypoglycemia occurring only in the fasting state (>12 hours fast);
Current diabetes, defined as hemoglobin A1c >6.5% or use of diabetes medications, except for acarbose or miglitol;
Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
Hepatic disease, including serum ALT or AST greater than 2 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0;
Trial design
Design model
Parallel
Treatments tested in this trial
Glucagon for Injection (Fresenius Kabi USA)
DrugThe investigators are assessing glucagon metabolism in individuals with and without PBH in fasting and post-prandial states.
[6,6-2H2] glucose
DrugThe investigators are using a stable isotope glucose tracer to assess glucose metabolism in individuals with and without PBH in fasting and post-prandial states.
[13C9, 15N1]-glucagon
DrugThe investigators are assessing the metabolism of glucagon in individuals with and without PBH in fasting and post-prandial states.
[1-13C] glucose
DrugThe investigators are assessing the metabolism of glucose in individuals with and without PBH in fasting and post-prandial states.
[2-13C] glucose
DrugThe investigators assessing the metabolism of glucose in individuals with and without PBH in fasting and post-prandial states.
Treatment groups
40 Participants
are divided into 2 treatment groupsGroup A: RYGB non-hypoglycemiaActive comparator 5 interventions
Group B: Post-Bariatric Hypoglycemia (PBH)Experimental treatment 5 interventions
Trial outcomes
Primary outcomes
1
Between-group differences in iAUC for postprandial EGP
Between-group differences in endogenous glucose production (EGP) in the postprandial state, as quantified by iAUC for postprandial EGP. These measurements will be taken at baseline and after mixed-meal consumption, specifically at minutes 10, 20, 30, 60, 90, 120, 150, and 180.
Time frame
During Visit 2, within 10 days of the baseline visitSecondary outcomes
1
Between-group differences in the integrated postprandial response (iAUC) of Ra glucagon
Between-group differences in glucagon secretion (Ra glucagon) in the postprandial state during mixed meal testing, as quantified by integrated postprandial response (iAUC) of Ra glucagon. These measurements will be taken at baseline and after mixed-meal consumption, specifically at minutes 10, 20, 30, 60, 90, 120, 150, and 180.
Time frame
During Visit 2, within 10 days of the baseline visit2
Between-group differences in EGP in the fasting state
Between-group differences in EGP in the fasting state, as quantified by fasting EGP. Samples will be collected at baseline before consumption of a mixed meal. This will be measured at baseline.
Time frame
During Visit 2, within 10 days of the baseline visit3
Between-group differences in iAUC for glucose levels for 60 minutes after postprandial glucagon administration
Between-group differences in glycemic response to exogenous glucagon administration in the postprandial state, following mixed meal testing, as quantified by iAUC glucose for 60 minutes after postprandial glucagon administration. This will be measured at the end of mixed meal testing (180 minutes) and then every 10 minutes for up to 60 minutes.
Time frame
During Visit 2, within 10 days of the baseline visit4
Between-group differences in insulin sensitivity, as estimated by postprandial SI derived from oral glucose minimal model
Between-group differences in insulin sensitivity, as estimated by postprandial SI derived from oral glucose minimal model. This will be measured after mixed-meal consumption (timepoints 0 minutes).
Time frame
During Visit 2, within 10 days of the baseline visitSponsors and contacts
Click on the lead sponsor to view all of their trials.
Joslin Diabetes Center
Lead sponsor
University of Alabama at Birmingham
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
Source ClinicalTrials.gov