A Phase 4 interventional study of Glucagon for Injection (Fresenius Kabi USA) and [6,6-2H2] glucose in Hypoglycemia, Hypoglycemia, Reactive and Bariatric Surgery, sponsored by Joslin Diabetes Center. Recruiting at 2 sites in United States. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-14.
Sponsored by Joslin Diabetes Center · Phase 4, Interventional, and Basic science
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.
The purpose of this study is to assess post-prandial carbohydrate, hormone, and hepatic glycogen metabolism comparing individuals with post-bariatric surgery hypoglycemia (PBH+) to individuals post-bariatric surgery without hypoglycemia (PBH-). There will be 3 visits to the study center in total.
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.
During Visit 1, the participants will undergo a medical history, physical examination, vital signs, and ECG; inclusion/exclusion criteria will be assessed. Participants will also be advised to complete food log entries and to follow a low glycemic index diet.
At Visit 2, a continuous glucose monitor (CGM sensor) in masked mode will be placed on the participant.
During Visit 3, participants will undergo infusions of glucose, glucagon, and their respective isotope tracers, and will consume a triple tracer mixed meal containing labeled glucose. The participants will complete C13 MRS scans to estimate liver glycogen content. Participants at Joslin Diabetes Center will not have MRS; response to an exogenous subcutaneous glucagon injection in the post-prandial state will be assessed instead. Blood samples will be processed and stored for subsequent analysis.
706 studies on the registry are indexed under Hypoglycemia; 94 are open to participants now.
This study's planned enrollment of 40 is above the median of 28 across 534 interventional studies indexed under Hypoglycemia.
Browse Hypoglycemia studies →Joslin Diabetes Center is the lead sponsor of 80 studies on the registry; 7 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Individuals that underwent Roux-en-y gastric bypass (RYGB) at least 2 years prior to recruitment and do not have a diagnosis of PBH.
Drug: Glucagon for Injection (Fresenius Kabi USA) · Drug: [6,6-2H2] glucose · Drug: [13C9, 15N1]-glucagon · Drug: [1-13C] glucose · Drug: [2-13C] glucose
Individuals that underwent RYGB at least 2 years prior to recruitment and have a diagnosis of PBH.
Drug: Glucagon for Injection (Fresenius Kabi USA) · Drug: [6,6-2H2] glucose · Drug: [13C9, 15N1]-glucagon · Drug: [1-13C] glucose · Drug: [2-13C] glucose
The investigators are assessing glucagon metabolism in individuals with and without PBH in fasting and post-prandial states.
The investigators are using a stable isotope glucose tracer to assess glucose metabolism in individuals with and without PBH in fasting and post-prandial states.
The investigators are assessing the metabolism of glucagon in individuals with and without PBH in fasting and post-prandial states.
The investigators are assessing the metabolism of glucose in individuals with and without PBH in fasting and post-prandial states.
The investigators assessing the metabolism of glucose in individuals with and without PBH in fasting and post-prandial states.
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 visit
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 visit
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 visit
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 visit
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 visit
Between-group differences in insulin secretion, as estimated by postprandial phi total
Between-group differences in insulin secretion, as estimated by postprandial phi total, derived from oral glucose minimal model. This will be measured after mixed-meal consumption (timepoint 0 minutes).
Time frame: During Visit 2, within 10 days of the baseline visit
Between-group differences in disposition index derived from oral glucose minimal model
Between group differences in disposition index, as estimated by postprandial DI, derived from oral glucose minimal model. This will be measured after mixed-meal consumption (timepoint 0 minutes).
Time frame: During Visit 2, within 10 days of the baseline visit
Between-group differences in basal glycogen content, measured by MRI
Glycogen content will be measured using magnetic resonance imaging (MRI). Spectroscopy will be performed using a 3-Tesla whole-body MR imager/spectrometer. Absolute glycogen concentrations will be calculated from the integrated area of the C1-glycogen signal at 100.1 parts per million referenced to a glycogen phantom, corrected for receiver gain and reception sensitivity. This measurement by MRI will only occur at the University of Alabama at Birmingham.
Time frame: During Visit 2, within 10 days of the baseline visit.
Between-group differences in meal-stimulated changes in glycogen content, measured by change from baseline
Glycogen content will be measured using magnetic resonance imaging (MRI). Spectroscopy will be performed using a 3-Tesla whole-body MR imager/spectrometer. Absolute glycogen concentrations will be calculated from the integrated area of the C1-glycogen signal at 100.1 parts per million referenced to a glycogen phantom, corrected for receiver gain and reception sensitivity. This measurement by MRI will only occur at the University of Alabama at Birmingham.
Time frame: During Visit 2, within 10 days of the baseline visit
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Deidentified participant data may be shared with other researchers with permission of local institutional review boards.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: 6 months after publication of study results
Access criteria: Data will be shared with academic investigators with approval of local institutional review boards.
Started Jan 2026 (actual). Primary completion is estimated for Jan 2027, 12 months after the start.
Of 18 phase 4 interventional studies under Hypoglycemia, half reached primary completion within 20 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 35. This study's planned 12 months is below that.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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Studies of the drugs tested here: Glucagon · Glucose
Joslin Diabetes Center