Role of Nutrient Transit in Hyperinsulinemic Hypoglycemia

Study Overview
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Brief Summary
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Severe hypoglycemia (low blood sugar)after gastric bypass surgery is an increasingly recognized condition, characterized by symptoms of hypoglycemia after eating and inappropriately elevated insulin concentrations that occur at the time of hypoglycemia. Severe hypoglycemia can be dangerous and debilitating and can also impact cognitive function. At the moment no medical therapies have been developed for this disorder. Determining why some but not other patients develop this condition would allow for improved prediction, prevention, and treatment approaches. The purpose of the study is to understand the physiological changes observed in those patients who undergo gastric bypass and develop symptomatic hypoglycemia.

Official Title
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Role of Nutrient Transit and Incretin Hormones in Hyperinsulinemic Hypoglycemia

Conditions
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Post-Bariatric Hypoglycemia

Intervention / Treatment
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* Behavioral: Use of Continuous Glucose Monitor (CGM)
* Other: Use of Cardea Solo monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients 18-70 years of age Post-bariatric surgery more than 6 months prior to signing the informed consent (not required for non-surgical controls) Documented history of hyperinsulinemic hypoglycemia (not required for post-bariatric and non-surgical controls) Exclusion Criteria: Patients currently using sulfonylureas or other medications that may interfere with glucose metabolism within 5 half-lives of drug. Participation in any clinical investigation within 4 weeks prior to dosing History of or current insulinoma Active infection or significant acute illness within 2 weeks prior to dosing Female patients who are pregnant or lactating Women of childbearing potential and not utilizing effective contraceptive methods Inadequate end organ function as defined by: Serum creatinine >2.0 mg/dL, alanine transaminase (ALT) and aspartate aminotransferase (AST) > 2 x Upper Normal Limit Allergy to test meal or medications used in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remote Phase: Post-Bariatric Hypoglycemia Patients<br>Participants will wear continuous glucose monitor (CGM) in a blinded manner (cannot see data output) for 20 days followed by in an unblinded manner (can see data output) for 20 days. | Behavioral: Use of Continuous Glucose Monitor (CGM)<br>* Participants will wear CGM<br>Other: Use of Cardea Solo monitoring<br>* Participants will wear a Cardea Solo patch during blinded CGM use<br>|
| No Intervention: In-Clinic Phase: Post-Bariatric Hypoglycemia Patients<br>Participants will attend 1-3 study visits over the period of approximately 2 months, with metabolic parameters assessed under a variety of conditions. This group will also wear CGM during a portion of the metabolic tests. This may include participants from the Remote Phase or newly enrolled participants. | |
| No Intervention: In-Clinic Phase: Surgical Controls<br>Participants will attend 1-3 study visits over the period of approximately 2 months, with metabolic parameters assessed under a variety of conditions. | |
| No Intervention: In-Clinic Phase: Nonsurgical Controls<br>Participants will attend 1-3 study visits over the period of approximately 2 months, with metabolic parameters assessed under a variety of conditions. | |
| No Intervention: In-Clinic Phase: Post-Bariatric Hypoglycemia Patients with indwelling gastrostomy tube<br>Participants will undergo standardized mixed meal tolerance tests via oral, gastrostomy tube, and concomitant oral + gastrostomy tube routes of delivery with metabolic parameters assessed. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steady state plasma glucose (SSPG) as a measure of insulin sensitivity | This endpoint applies to the In-Clinic Phase cohorts: Post-Bariatric Hypoglycemia, Surgical Controls, Non-Surgical Controls. This is a one day in-person appointment lasting approximately 6 hours. | Baseline 4-hour SSPG | 
| Rate of gastric emptying | This endpoint applies to the In-Clinic Phase cohorts: Post-Bariatric Hypoglycemia, Surgical Controls, Non-Surgical Controls. This is an in-person appointment lasting approximately 5 hours. | Baseline 4-hour scintigraphy procedure | 
| Concentration of Glucagon-Like peptide 1 secretion augmentation of insulin secretion rate | This endpoint applies to the In-Clinic Phase cohorts: Post-Bariatric Hypoglycemia, Surgical Controls, Non-Surgical Controls. The blood collected from the SSPG will be stored and analyzed for the concentration of GLP-1 at multiple timepoints. | Baseline 4-hour graded-glucose infusion | 
| Rate of clinically important hypoglycemia (Level 2 hypoglycemia, <54 mg/dL) | This endpoint applies to Remote Phase participants | 40 days | 
| Percent time in clinically important hypoglycemia (Level 2 hypoglycemia, <54 mg/dL) | This endpoint applies to Remote Phase participants | 40 days | 
| Rate of arrhythmia during hypoglycemia | This endpoint applies to Remote Phase participants | 10 days |