Mechanisms of Hypoglycemia in Patients Without Diabetes

NCT ID: NCT04428723

Last Updated: 2024-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

33 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-08-11

Study Completion Date

2025-06-30

Brief Summary

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The goal of this study is to identify physiologic and molecular mechanisms that underlie hypoglycemia in the absence of diabetes (or medications that can cause hypoglycemia) and to investigate potential genetic and microbiome differences which contribute to hypoglycemia. We will test the hypothesis that hypoglycemia in the absence of diabetes is linked to genetic variation or the microbiome, and identify whether additional medical history or diagnoses are enriched in the population of patients with hypoglycemia.

Detailed Description

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Although there are several conditions which have been identified that cause, or contribute to hypoglycemia, diagnosis can be challenging, as the physiologic, and molecular mechanisms are incompletely understood. Additionally, treatment options are relatively limited, and often incompletely effective and/or not well tolerated. Investigating the causative factors and mechanisms of hypoglycemia is important therefore in improving our understanding in order to develop new and more effective approaches to treatment.

The current study aims to:

1. more fully characterize clinical history and demographics in patients with diverse forms of hypoglycemia by creating and analyzing a patient database;
2. for a subset of patients, characterize metabolic and hormonal responses to a standard meal;
3. analyze DNA variants in individuals with hypoglycemia;
4. analyze differences in the intestinal microbiome in individuals with hypoglycemia.

Conditions

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Hypoglycemia

Keywords

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Microbiome DNA Hormones Genetics

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Hypoglycemia, no upper gastrointestinal (GI) surgery

Males or females with hypoglycemia with neuroglycopenia, but no history of upper GI surgery, diabetes or prediabetes

Entry of demographic and medical history data into a deidentified database

Intervention Type OTHER

Entry into repository for analysis.

Blood sample for DNA analysis

Intervention Type GENETIC

Targeted resequencing of DNA to identify variants associated with hypoglycemia, comparing participants with hypoglycemia (both surgical and non-surgical) and healthy controls.

Stool sample for microbiome analysis

Intervention Type DIAGNOSTIC_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.

Mixed meal tolerance test

Intervention Type DIAGNOSTIC_TEST

For a subset of participants: 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.

Continuous glucose monitoring

Intervention Type DIAGNOSTIC_TEST

A CGM sensor (Dexcom G4 or other professional version available at onset of study) will be placed 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 monitor

Intervention Type DIAGNOSTIC_TEST

The activity monitor (Fitbit Charge 2) will be worn by participants for 10 days, to assess activity, concurrent with CGM sensor wear.

Hypoglycemia, with history of upper GI surgery

Males or females with hypoglycemia with neuroglycopenia, with history of upper GI surgery

Entry of demographic and medical history data into a deidentified database

Intervention Type OTHER

Entry into repository for analysis.

Blood sample for DNA analysis

Intervention Type GENETIC

Targeted resequencing of DNA to identify variants associated with hypoglycemia, comparing participants with hypoglycemia (both surgical and non-surgical) and healthy controls.

Stool sample for microbiome analysis

Intervention Type DIAGNOSTIC_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.

Mixed meal tolerance test

Intervention Type DIAGNOSTIC_TEST

For a subset of participants: 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.

Continuous glucose monitoring

Intervention Type DIAGNOSTIC_TEST

A CGM sensor (Dexcom G4 or other professional version available at onset of study) will be placed 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 monitor

Intervention Type DIAGNOSTIC_TEST

The activity monitor (Fitbit Charge 2) will be worn by participants for 10 days, to assess activity, concurrent with CGM sensor wear.

Controls, without hypoglycemia or upper GI surgery

Males or females with no history of upper gastrointestinal surgery, hypoglycemia, or diabetes.

Entry of demographic and medical history data into a deidentified database

Intervention Type OTHER

Entry into repository for analysis.

Blood sample for DNA analysis

Intervention Type GENETIC

Targeted resequencing of DNA to identify variants associated with hypoglycemia, comparing participants with hypoglycemia (both surgical and non-surgical) and healthy controls.

Stool sample for microbiome analysis

Intervention Type DIAGNOSTIC_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.

Mixed meal tolerance test

Intervention Type DIAGNOSTIC_TEST

For a subset of participants: 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.

Continuous glucose monitoring

Intervention Type DIAGNOSTIC_TEST

A CGM sensor (Dexcom G4 or other professional version available at onset of study) will be placed 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 monitor

Intervention Type DIAGNOSTIC_TEST

The activity monitor (Fitbit Charge 2) will be worn by participants for 10 days, to assess activity, concurrent with CGM sensor wear.

Interventions

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Entry of demographic and medical history data into a deidentified database

Entry into repository for analysis.

Intervention Type OTHER

Blood sample for DNA analysis

Targeted resequencing of DNA to identify variants associated with hypoglycemia, comparing participants with hypoglycemia (both surgical and non-surgical) and healthy controls.

Intervention Type GENETIC

Stool sample for microbiome analysis

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.

Intervention Type DIAGNOSTIC_TEST

Mixed meal tolerance test

For a subset of participants: 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.

Intervention Type DIAGNOSTIC_TEST

Continuous glucose monitoring

A CGM sensor (Dexcom G4 or other professional version available at onset of study) will be placed 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.

Intervention Type DIAGNOSTIC_TEST

activity monitor

The activity monitor (Fitbit Charge 2) will be worn by participants for 10 days, to assess activity, concurrent with CGM sensor wear.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Meal Testing

Eligibility Criteria

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Inclusion Criteria

1. For hypoglycemia group without a history of bariatric surgery: Males or females diagnosed with hypoglycemia with prior episodes of neuroglycopenia.
2. For hypoglycemia group with history of upper gastrointestinal surgery: Males or females diagnosed with ongoing hypoglycemia with prior episodes of neuroglycopenia.
3. For non-surgical controls only: Males or females with no history of upper gastrointestinal surgery and no history of hypoglycemia or diabetes.
4. Age 18-70 years of age, inclusive, at screening.
5. Willingness to provide informed consent and attend one study visit, with option to attend a second visit with mixed meal test, and follow all study procedures

Exclusion Criteria

1. Active treatment with any diabetes medications except for acarbose;
2. Known insulinoma, gastrinoma, or other neuroendocrine tumor;


1. Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
2. Hepatic disease, including serum alanine transaminase (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;
3. Congestive heart failure, New York Hear Association (NYHA) class II, III or IV;
4. 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;
5. History of syncope (unrelated to hypoglycemia) or diagnosed cardiac arrhythmia;
6. Concurrent administration of β-blocker therapy;
7. History of a cerebrovascular accident;
8. Seizure disorder (other than with suspect or documented hypoglycemia);
9. Active malignancy, except basal cell or squamous cell skin cancers;
10. Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease);
11. Major surgical operation within 30 days prior to screening;
12. Hematocrit \< 33% (women) or \<36% (men);
13. Bleeding disorder, treatment with warfarin, or platelet count \<50,000;
14. Blood donation (1 pint of whole blood) within the past 2 months;
15. Active alcohol abuse or substance abuse;
16. Current administration of oral or parenteral corticosteroids;
17. 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 (IUD), the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence.
18. 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Joslin Diabetes Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mary Elizabeth Patti, MD

Role: PRINCIPAL_INVESTIGATOR

Joslin Diabetes Center

Locations

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Joslin Diabetes Center

Boston, Massachusetts, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Informed Consent Form

View Document

Related Links

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http://www.joslin.org/research/clinical-research/clinical-trials/

recruitment website with contact information

Other Identifiers

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00000095

Identifier Type: -

Identifier Source: org_study_id