Role of GLP-1 in Hyperinsulinemic Hypoglycemia Post-bariatric Surgery

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the role of GLP-1 in causing extreme postprandial glucose reductions after bariatric surgery in a subset of patients who have severe symptomatic hypoglycemia.

Detailed Description
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The physiologic mechanisms mediating the glucose-lowering effect of Roux-en-Y Gastric Bypass (RYGB) or post-Vertical Sleeve Gastrectomy (VSG) are unknown. The reduction in glucose excursions prior to weight loss has lead to postulates that the incretin hormone, GLP-1, may play an important role. The purpose of this study is to evaluate the role of GLP-1 in causing extreme postprandial glucose reductions in a subset of post-bariatric patients through the pharmacologic blockade of the GLP-1 receptor in post-RYGB or post-VSG patients with severe symptomatic hypoglycemia.

Official Title
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The Role of GLP-1 in Mediating Glucose Reductions After Bariatric Surgery

Conditions
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Hypoglycemia

Intervention / Treatment
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* Drug: Exendin (9-39)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ages 18-65 BMI 25-40 with a clinical diagnosis of severe symptomatic hypoglycemia after bariatric surgery Exclusion Criteria: Acute medical illness, such as acute bacterial or viral syndrome, febrile illness, acute abdominal symptoms, orthopedic injury within one week History of cardiac failure, renal insufficiency (estimated Crcl<30cc/min), hepatic insufficiency, chronic obstructive pulmonary disease, anemia (Hct<30%), or uncontrolled hypertension (SBP>160 or DBP>100) Pregnancy Use of medications that affect glucose metabolism Fasting glucose >150 or HbA1c>7.5 on Metformin Women of childbearing potential (will have a pregnancy test, in addition use of abstinence for at least one month prior to study or use two types of contraceptives, hormonal implant or Depo Provera) Active, uncontrolled psychiatric disease Participating in other studies or have received investigational medications within the past month or 5 half-lives of the drug, whichever is longer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exendin(9-39)<br>IV infusion of Exendin (9-39). | Drug: Exendin (9-39)<br>* IV infusion of Exendin (9-39) during standardized oral glucose tolerance test (OGTT).<br>|
| Placebo Comparator: Placebo<br>IV infusion of normal saline | Other: Placebo<br>* IV infusion of Placebo (normal saline) during standardized oral glucose tolerance test (OGTT)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma glucose area under the curve |  | 0 to 180 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma insulin area under the curve |  | 0 to 180 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperinsulinemic, post-bariatric surgery