HypoglycemiaNCT04428866
Mechanisms of Post-Bariatric Hypoglycemia
An observational study of Hypoglycemia, run by Joslin Diabetes Center at 1 site in United States.
Trial summary
Post-bariatric hypoglycemia (PBH) is an increasingly recognized syndrome that is incompletely understood. The purpose of this study is to increase our level of understanding by investigating mechanisms contributing to this condition. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypoglycemia
- What is being tested?
- Continuous Glucose Monitoring, activity monitor and Mixed meal tolerance test
- Type of treatment
- Injection or infusion
- How many people
- 105 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Feb 2020to Sep 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Individuals with post-bariatric hypoglycemia will be recruited from the the Joslin Hypoglycemia Clinic. Individuals who have had RYGB but have no symptoms of hypoglycemia will be recruited from local bariatric programs and via advertisement. Control individuals will be recruited via advertisement locally.
Who may be able to join
- For PBH group only: Males or females diagnosed with ongoing post-bariatric hypoglycemia with prior episodes of neuroglycopenia, unresponsive to dietary intervention (low glycemic index, controlled carbohydrate portions) and trial of acarbose therapy at the maximally tolerated dose.
- For post-RYGB group without PBH: Males or females with history of RYGB and no history of symptomatic hypoglycemia.
- For non-surgical controls only: Males or females with no history of upper gastrointestinal surgery and no history of hypoglycemia or diabetes.
- Age 18-70 years of age, inclusive, at screening.
- Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits.
Who cannot join
- Documented hypoglycemia occurring in the fasting state (> 12 hours fast);
- Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
- Hepatic disease, including serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0;
- Congestive heart failure, New York Heart Association class II, III or IV;
- History of myocardial infarction, unstable angina or revascularization within the past 6 months or 2 or more risk factors for coronary artery disease including diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, and active tobacco use.
- History of syncope (unrelated to hypoglycemia) or diagnosed cardiac arrhythmia
Show all 22Show fewer
- Concurrent administration of β-blocker therapy;
- History of a cerebrovascular accident;
- Seizure disorder (other than with suspect or documented hypoglycemia);
- Active treatment with any diabetes medications except for acarbose;
- Active malignancy, except basal cell or squamous cell skin cancers;
- Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease);
- Known insulinoma;
- Major surgical operation within 30 days prior to screening;
- Hematocrit < 33% (women) or <36% (men);
- Bleeding disorder, treatment with warfarin, or platelet count <50,000;
- Blood donation (1 pint of whole blood) within the past 2 months;
- Active alcohol abuse or substance abuse;
- Current administration of oral or parenteral corticosteroids;
- Pregnancy and/ or Lactation: For women of childbearing potential: there is a requirement for a negative urine pregnancy test and for agreement to use contraception during the study and for at least 1 month after participating in the study. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an intrauterine device, the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence.
- Use of an investigational drug within 30 days prior to screening.
- There will be no involvement of special vulnerable populations such as fetuses, neonates, pregnant women, children, prisoners, institutionalized or incarcerated individuals, or others who may be considered vulnerable populations.
Trial locations and contacts
1 site in 1 country.
About this study
Post-bariatric hypoglycemia (PBH) is an increasingly recognized syndrome that is incompletely understood.
The purpose of this study is to increase our level of understanding by investigating mechanisms contributing to this condition.
Read more
Participation in this study will take place over four visits, which will include the following:
- Wearing of a continuous glucose monitoring device;
- Providing a stool sample (collected at home);
- Measuring glucose and hormone levels in response to a meal;
- Measuring glucose and hormone levels in response to an injection of glucagon;
- Measuring hormone levels while glucose levels are gradually lowered, and during a controlled period of a low glucose level (hypoglycemic clamp).
Investigators will test the hypothesis that counterregulatory hormone responses are impaired in individuals with PBH, and that differences in the intestinal bacteria (microbiome) may contribute to this condition.
Read the detailed description
Bariatric surgery is increasingly recognized as a potent tool for the treatment of type 2 diabetes (T2D), yielding not only weight loss but also rapid improvements in glycemia allowing discontinuation of diabetes-related medication within days after surgery. However, along with this metabolic success comes an increased incidence of severe hypoglycemia (termed post-bariatric hypoglycemia; PBH) for a subset of individuals.
The goal of these studies is to identify physiological and molecular mechanisms that underlie PBH, to determine whether these changes also contribute to surgery-induced improvements in glucose regulation (homeostasis), and to define potential new therapeutic interventions for PBH.
Participation in this study will take place over four visits, which will include the following:
- Detailed history, physical exam, and laboratory testing to determine study eligibility
- Assessment of glucose patterns using a masked continuous glucose monitor;
- Analysis of a stool sample (collected at home);
- Measuring glucose and hormone levels in response to a meal;
- Measuring glucose and hormone levels in response to an injection of glucagon;
- Measuring hormone levels while glucose levels are gradually lowered, and during a controlled period of a low glucose level (hypoglycemic clamp).
Investigators will test the hypothesis that counterregulatory hormone responses are impaired in individuals with PBH, and that differences in the intestinal bacteria (microbiome) and hormones produced in response to a meal may contribute to this condition.
- Conditions
- Hypoglycemia
- Being tested
- Continuous Glucose Monitoring, activity monitor, Mixed meal tolerance test, Glucagon Sensitivity Testing, Hypoglycemic Hyperinsulinemic Clamp
- Keywords
- Post-Bariatric Hypoglycemia, Roux-en-Y gastric bypass, Bariatric Surgery, Hypoglycemic clamp, Hormones, Microbiome
- Medical subject headings
- Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous Glucose MonitoringDiagnostic test
A CGM sensor (Dexcom G4 or other professional version available at onset of study) will be placed during visit 1 in blinded (masked) mode, and will be worn for 10 days. Data will be analyzed to determine patterns of glucose during both day and night intervals.
activity monitorDiagnostic test
The activity monitor (Fitbit Charge 2) will be worn by participants for 10 days to assess activity, concurrent with CGM sensor wear.
Mixed meal tolerance testDiagnostic test
Also called meal test
After an overnight fast, participants will be given a standard liquid mixed meal; blood samples will be collected at baseline (fasting) and at defined time points after a meal for metabolic and hormonal analyses.
Glucagon Sensitivity TestingDiagnostic test
After baseline blood sampling, glucagon will be administered by injection, and blood samples will be collected for analysis of glucose and hormone responses. This will allow us to assess whether sensitivity to glucagon is altered in PBH.
Hypoglycemic Hyperinsulinemic ClampDiagnostic test
Also called Hyperinsulinemic Hypoglycemic Clamp
This test will assess hormonal responses to hypoglycemia. Participants will arrive after an overnight fast. After baseline blood sampling, an infusion of insulin and glucose will be started, and infusions will be adjusted to allow glucose levels to drop very gradually. Blood samples will be collected for measurement of hormonal responses to lowering of glucose. This test will allow us to determine whether secretion of hormones which counteract hypoglycemia (counterregulatory hormones) is reduced in patients with PBH as compared with other groups.
analysis of fecal microbiomeDiagnostic test
Participants will be asked to provide a fecal sample, collected at home, which will be analyzed to determine the types of bacteria present in the feces.
| Study group | Role | What they receive |
|---|---|---|
| Participants with post-bariatric hypoglycemia | Individuals with history of Roux-en-Y gastric bypass surgery, who have a history of hypoglycemia will be recruited from the Joslin Hypoglycemia Clinic. Receives: Diagnostic Test: Continuous Glucose Monitoring; Diagnostic Test: activity monitor; Diagnostic Test: Mixed meal tolerance test; Diagnostic Test: Glucagon Sensitivity Testing; Diagnostic Test: Hypoglycemic Hyperinsulinemic Clamp; Diagnostic Test: analysis of fecal microbiome | |
| Asymptomatic participants with Roux-en-Y gastric bypass (RYGB) | Individuals with history of RYGB, without a history of or symptoms of hypoglycemia will be recruited from local postoperative surgical clinics and from the community. Receives: Diagnostic Test: Continuous Glucose Monitoring; Diagnostic Test: activity monitor; Diagnostic Test: Mixed meal tolerance test; Diagnostic Test: Glucagon Sensitivity Testing; Diagnostic Test: Hypoglycemic Hyperinsulinemic Clamp; Diagnostic Test: analysis of fecal microbiome | |
| Control group | Individuals without a history of bariatric surgery will be recruited by local advertisement. Receives: Diagnostic Test: Continuous Glucose Monitoring; Diagnostic Test: activity monitor; Diagnostic Test: Mixed meal tolerance test; Diagnostic Test: Glucagon Sensitivity Testing; Diagnostic Test: Hypoglycemic Hyperinsulinemic Clamp; Diagnostic Test: analysis of fecal microbiome |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolic responses during experimental hypoglycemia induced by hypoglycemic clamp and/or mixed meal testing
Metabolites will be measured at set time points after the start of insulin or mixed meal. For the hypoglycemic clamp, a time-trend analysis will be performed to identify the glucose level at which each metabolite rises significantly above the linear average of its preceding values. Linear mixed effects modeling will be utilized to identify group- and time-dependent differences in metabolite responses. Data will be checked to ensure variables conform to assumptions of the analysis. Sensitivity analysis will determine whether missing data are randomly associated with clinical or experimental phenotypes, and assess the impact of missing data on conclusions. Relationships between clinical and metabolic variables will be analyzed using Pearson correlation, and adjusted for multiple comparisons using Benjamini-Hochberg testing.
Measured: July 2023
Hormonal responses during experimental hypoglycemia induced by hypoglycemic clamp and/or mixed meal testing
Counterregulatory hormones will be measured at set time points after the start of insulin or mixed meal. For the hypoglycemic clamp, a time-trend analysis will be performed to identify the glucose level at which each hormone rises significantly above the linear average of its preceding values. Linear mixed effects modeling will be utilized to identify group- and time-dependent differences in counterregulatory hormone responses. Data will be checked to ensure variables conform to assumptions of the analysis. Sensitivity analysis will determine whether missing data are randomly associated with clinical or experimental phenotypes, and assess the impact of missing data on conclusions. Relationships between clinical and hormonal variables will be analyzed using Pearson correlation, and adjusted for multiple comparisons using Benjamini-Hochberg testing.
Measured: July 2023
Assessment of glucagon responsiveness during glucagon stimulation testing
Glucose response to glucagon will be assessed by measurement of glucose levels at baseline, and at set time points after glucagon injection. Linear mixed effects modeling will be utilized to identify group- and time-dependent differences in glucose response to glucagon. Relationships between clinical variables and glucose levels in response to glucagon will be analyzed using Pearson correlation, and adjusted for multiple comparisons using Benjamini-Hochberg testing.
Measured: July 2023
Assessment of hormonal responses during glucagon stimulation testing
Hormonal response to glucagon will be assessed by measurement of hormone levels at baseline, and at a set time point after glucagon injection. Linear mixed effects modeling will be utilized to identify group- and time-dependent differences in hormonal response to glucagon. Relationships between clinical variables, glucose levels, and hormonal levels in response to glucagon will be analyzed using Pearson correlation, and adjusted for multiple comparisons using Benjamini-Hochberg testing.
Measured: July 2023
Analysis of microbiome differences in patients with PBH
Microbiome will be characterized by sequencing to obtain metagenomic data and pathway analysis; all data will be adjusted for multiple comparisons.
Measured: July 2023
Secondary outcomes (3)
Correlation between counterregulatory hormone response to experimental hypoglycemia and magnitude of hypoglycemia as determined by continuous glucose monitoring (CGM)
CGM data will be analyzed to assess mean, median, peak, and nadir sensor glucose values, glycemic variability (GV), severity and length of hypoglycemia (% time glucose <70, <60, <54 mg/dL), and number and duration of severe hypoglycemia (sensor glucose <54, duration >15 minutes) will be quantified. Metrics will be assessed over 24 hours and during daytime (6 AM to midnight) and nighttime (midnight to 6 AM) independently. Magnitude of hypoglycemia will be correlated with counterregulatory hormone levels during experimental hypoglycemia.
Measured: July 2023
Correlation between hypoglycemia frequency (as determined by CGM) and microbiome
Metagenomic data will be correlated with hypoglycemia frequency determined by CGM.
Measured: July 2023
Correlation between hypoglycemia frequency (as determined by CGM) and counterregulatory hormones.
Hypoglycemia data (from CGM) will be correlated with counterregulatory hormone response to experimental hypoglycemia.
Measured: July 2023
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start26 Feb 2020
- Primary completionSep 2024 (estimated)
- Study completionSep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypoglycemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joslin Diabetes Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Michigan
- Responsible party
- Sponsor
- Investigators
- Mary Elizabeth Patti, MD, Principal investigator, Joslin Diabetes Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04428866
- Sponsor's protocol ID
- STUDY00000074
- Status last verified
- Jan 2024
- First submitted
- 14 Nov 2019
- Last updated
- 5 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified participant data may be shared with other researchers with permission of local institutional review boards.
Publications
Ferraz-Bannitz R, Pei L, Wang H, Ozturk B, Casanova Querol P, Goncalves da Cruz A, Cook TM, Saeed H, Osterwalder L, Poulos L, Saifeldin H, Cummings C, Farahmandsadr M, Amore A, Sheehan A, Simonson DC, Sandoval DA, Patti ME. Plasma GDF15 increases during hyperinsulinemic hypoglycemia in humans with post-bariatric hypoglycemia and after insulin exposure in mice. Cell Rep Med. 2026 Mar 17;7(3):102656. doi: 10.1016/j.xcrm.2026.102656. Epub 2026 Mar 9.
PubMed 41806840
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Post-Bariatric Hypoglycemia
- ClinicalTrials.gov ID
- NCT04428866
- Acronym / sponsor ID
- STUDY00000074
- Conditions
- Hypoglycemia
- Keywords
- Post-Bariatric Hypoglycemia, Roux-en-Y gastric bypass, Bariatric Surgery, Hypoglycemic clamp, Hormones, Microbiome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Joslin Diabetes CenterUniversity, hospital or other
- Collaborators
- University of Michigan
- Study start
- 26 Feb 2020 (actual)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Sep 2024 (estimated)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Post-bariatric hypoglycemia (PBH) is an increasingly recognized syndrome that is incompletely understood.
The purpose of this study is to increase our level of understanding by investigating mechanisms contributing to this condition.
Participation in this study will take place over four visits, which will include the following:
- Wearing of a continuous glucose monitoring device;
- Providing a stool sample (collected at home);
- Measuring glucose and hormone levels in response to a meal;
- Measuring glucose and hormone levels in response to an injection of glucagon;
- Measuring hormone levels while glucose levels are gradually lowered, and during a controlled period of a low glucose level (hypoglycemic clamp).
Investigators will test the hypothesis that counterregulatory hormone responses are impaired in individuals with PBH, and that differences in the intestinal bacteria (microbiome) may contribute to this condition.
Detailed description
Bariatric surgery is increasingly recognized as a potent tool for the treatment of type 2 diabetes (T2D), yielding not only weight loss but also rapid improvements in glycemia allowing discontinuation of diabetes-related medication within days after surgery. However, along with this metabolic success comes an increased incidence of severe hypoglycemia (termed post-bariatric hypoglycemia; PBH) for a subset of individuals.
The goal of these studies is to identify physiological and molecular mechanisms that underlie PBH, to determine whether these changes also contribute to surgery-induced improvements in glucose regulation (homeostasis), and to define potential new therapeutic interventions for PBH.
Participation in this study will take place over four visits, which will include the following:
- Detailed history, physical exam, and laboratory testing to determine study eligibility
- Assessment of glucose patterns using a masked continuous glucose monitor;
- Analysis of a stool sample (collected at home);
- Measuring glucose and hormone levels in response to a meal;
- Measuring glucose and hormone levels in response to an injection of glucagon;
- Measuring hormone levels while glucose levels are gradually lowered, and during a controlled period of a low glucose level (hypoglycemic clamp).
Investigators will test the hypothesis that counterregulatory hormone responses are impaired in individuals with PBH, and that differences in the intestinal bacteria (microbiome) and hormones produced in response to a meal may contribute to this condition.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Participants with post-bariatric hypoglycemia | – | Diagnostic Test: Continuous Glucose Monitoring, Diagnostic Test: activity monitor, Diagnostic Test: Mixed meal tolerance test, Diagnostic Test: Glucagon Sensitivity Testing, Diagnostic Test: Hypoglycemic Hyperinsulinemic Clamp, Diagnostic Test: analysis of fecal microbiomeIndividuals with history of Roux-en-Y gastric bypass surgery, who have a history of hypoglycemia will be recruited from the Joslin Hypoglycemia Clinic. |
| Asymptomatic participants with Roux-en-Y gastric bypass (RYGB) | – | Diagnostic Test: Continuous Glucose Monitoring, Diagnostic Test: activity monitor, Diagnostic Test: Mixed meal tolerance test, Diagnostic Test: Glucagon Sensitivity Testing, Diagnostic Test: Hypoglycemic Hyperinsulinemic Clamp, Diagnostic Test: analysis of fecal microbiomeIndividuals with history of RYGB, without a history of or symptoms of hypoglycemia will be recruited from local postoperative surgical clinics and from the community. |
| Control group | – | Diagnostic Test: Continuous Glucose Monitoring, Diagnostic Test: activity monitor, Diagnostic Test: Mixed meal tolerance test, Diagnostic Test: Glucagon Sensitivity Testing, Diagnostic Test: Hypoglycemic Hyperinsulinemic Clamp, Diagnostic Test: analysis of fecal microbiomeIndividuals without a history of bariatric surgery will be recruited by local advertisement. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals with post-bariatric hypoglycemia will be recruited from the the Joslin Hypoglycemia Clinic. Individuals who have had RYGB but have no symptoms of hypoglycemia will be recruited from local bariatric programs and via advertisement. Control individuals will be recruited via advertisement locally.
Key inclusion criteria (5 listed)
- For PBH group only: Males or females diagnosed with ongoing post-bariatric hypoglycemia with prior episodes of neuroglycopenia, unresponsive to dietary intervention (low glycemic index, controlled carbohydrate portions) and trial of acarbose therapy at the maximally tolerated dose.
- For post-RYGB group without PBH: Males or females with history of RYGB and no history of symptomatic hypoglycemia.
- For non-surgical controls only: Males or females with no history of upper gastrointestinal surgery and no history of hypoglycemia or diabetes.
- Age 18-70 years of age, inclusive, at screening.
- Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits.
Key exclusion criteria (22 listed)
- Documented hypoglycemia occurring in the fasting state (> 12 hours fast);
- Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
- Hepatic disease, including serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0;
- Congestive heart failure, New York Heart Association class II, III or IV;
- History of myocardial infarction, unstable angina or revascularization within the past 6 months or 2 or more risk factors for coronary artery disease including diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, and active tobacco use.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuous Glucose MonitoringA CGM sensor (Dexcom G4 or other professional version available at onset of study) will be placed during visit 1 in blinded (masked) mode, and will be worn for 10 days. Data will be analyzed to determine patterns of glucose during both day and night intervals. | Diagnostic test | Asymptomatic participants with Roux-en-Y gastric bypass (RYGB), Control group, Participants with post-bariatric hypoglycemia |
| activity monitorThe activity monitor (Fitbit Charge 2) will be worn by participants for 10 days to assess activity, concurrent with CGM sensor wear. | Diagnostic test | Asymptomatic participants with Roux-en-Y gastric bypass (RYGB), Control group, Participants with post-bariatric hypoglycemia |
| Mixed meal tolerance testAlso: meal testAfter an overnight fast, participants will be given a standard liquid mixed meal; blood samples will be collected at baseline (fasting) and at defined time points after a meal for metabolic and hormonal analyses. | Diagnostic test | Asymptomatic participants with Roux-en-Y gastric bypass (RYGB), Control group, Participants with post-bariatric hypoglycemia |
| Glucagon Sensitivity TestingAfter baseline blood sampling, glucagon will be administered by injection, and blood samples will be collected for analysis of glucose and hormone responses. This will allow us to assess whether sensitivity to glucagon is altered in PBH. | Diagnostic test | Asymptomatic participants with Roux-en-Y gastric bypass (RYGB), Control group, Participants with post-bariatric hypoglycemia |
| Hypoglycemic Hyperinsulinemic ClampAlso: Hyperinsulinemic Hypoglycemic ClampThis test will assess hormonal responses to hypoglycemia. Participants will arrive after an overnight fast. After baseline blood sampling, an infusion of insulin and glucose will be started, and infusions will be adjusted to allow glucose levels to drop very gradually. Blood samples will be collected for measurement of hormonal responses to lowering of glucose. This test will allow us to determine whether secretion of hormones which counteract hypoglycemia (counterregulatory hormones) is reduced in patients with PBH as compared with other groups. | Diagnostic test | Asymptomatic participants with Roux-en-Y gastric bypass (RYGB), Control group, Participants with post-bariatric hypoglycemia |
| analysis of fecal microbiomeParticipants will be asked to provide a fecal sample, collected at home, which will be analyzed to determine the types of bacteria present in the feces. | Diagnostic test | Asymptomatic participants with Roux-en-Y gastric bypass (RYGB), Control group, Participants with post-bariatric hypoglycemia |
Primary outcome
Metabolic responses during experimental hypoglycemia induced by hypoglycemic clamp and/or mixed meal testing
Time frame: July 2023
Metabolites will be measured at set time points after the start of insulin or mixed meal. For the hypoglycemic clamp, a time-trend analysis will be performed to identify the glucose level at which each metabolite rises significantly above the linear average of its preceding values. Linear mixed effects modeling will be utilized to identify group- and time-dependent differences in metabolite responses. Data will be checked to ensure variables conform to assumptions of the analysis. Sensitivity analysis will determine whether missing data are randomly associated with clinical or experimental phenotypes, and assess the impact of missing data on conclusions. Relationships between clinical and metabolic variables will be analyzed using Pearson correlation, and adjusted for multiple comparisons using Benjamini-Hochberg testing.
Hormonal responses during experimental hypoglycemia induced by hypoglycemic clamp and/or mixed meal testing
Time frame: July 2023
Counterregulatory hormones will be measured at set time points after the start of insulin or mixed meal. For the hypoglycemic clamp, a time-trend analysis will be performed to identify the glucose level at which each hormone rises significantly above the linear average of its preceding values. Linear mixed effects modeling will be utilized to identify group- and time-dependent differences in counterregulatory hormone responses. Data will be checked to ensure variables conform to assumptions of the analysis. Sensitivity analysis will determine whether missing data are randomly associated with clinical or experimental phenotypes, and assess the impact of missing data on conclusions. Relationships between clinical and hormonal variables will be analyzed using Pearson correlation, and adjusted for multiple comparisons using Benjamini-Hochberg testing.
Assessment of glucagon responsiveness during glucagon stimulation testing
Time frame: July 2023
Glucose response to glucagon will be assessed by measurement of glucose levels at baseline, and at set time points after glucagon injection. Linear mixed effects modeling will be utilized to identify group- and time-dependent differences in glucose response to glucagon. Relationships between clinical variables and glucose levels in response to glucagon will be analyzed using Pearson correlation, and adjusted for multiple comparisons using Benjamini-Hochberg testing.
Assessment of hormonal responses during glucagon stimulation testing
Time frame: July 2023
Hormonal response to glucagon will be assessed by measurement of hormone levels at baseline, and at a set time point after glucagon injection. Linear mixed effects modeling will be utilized to identify group- and time-dependent differences in hormonal response to glucagon. Relationships between clinical variables, glucose levels, and hormonal levels in response to glucagon will be analyzed using Pearson correlation, and adjusted for multiple comparisons using Benjamini-Hochberg testing.
Analysis of microbiome differences in patients with PBH
Time frame: July 2023
Microbiome will be characterized by sequencing to obtain metagenomic data and pathway analysis; all data will be adjusted for multiple comparisons.
3 secondary outcomes
Correlation between counterregulatory hormone response to experimental hypoglycemia and magnitude of hypoglycemia as determined by continuous glucose monitoring (CGM)
Time frame: July 2023
Correlation between hypoglycemia frequency (as determined by CGM) and microbiome
Time frame: July 2023
Correlation between hypoglycemia frequency (as determined by CGM) and counterregulatory hormones.
Time frame: July 2023
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
- Derived from this study: PubMed 41806840Ferraz-Bannitz R, Pei L, Wang H, Ozturk B, Casanova Querol P, Goncalves da Cruz A, Cook TM, Saeed H, Osterwalder L, Poulos L, Saifeldin H, Cummings C, Farahmandsadr M, Amore A, Sheehan A, Simonson DC, Sandoval DA, Patti ME. Plasma GDF15 increases during hyperinsulinemic hypoglycemia in humans with post-bariatric hypoglycemia and after insulin exposure in mice. Cell Rep Med. 2026 Mar 17;7(3):102656. doi: 10.1016/j.xcrm.2026.102656. Epub 2026 Mar 9.
- Joslin Diabetes Center: Mechanisms of PBH recruitment website with contact informationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Deidentified participant data may be shared with other researchers with permission of local institutional review boards.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary Elizabeth Patti, MD principal investigator
Joslin Diabetes Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypoglycemia, run by Joslin Diabetes Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolic responses during experimental hypoglycemia induced by hypoglycemic clamp and/or mixed meal testing (time frame: July 2023). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04428866, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2024.