Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia

NCT ID: NCT02685852

Last Updated: 2021-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2019-07-22

Brief Summary

The purpose of the study is to evaluate the effectiveness of exenatide in adults experiencing episodes of hyperinsulinemic hypoglycemia following Roux-en-Y bariatric surgery.

Detailed Description

Roux-en-Y gastric bypass surgery (RYGB) is one of the most common bariatric surgeries in the United States and is generally highly effective for weight loss. Unfortunately, among the potential complications is hyperinsulinemic hypoglycemia. Though the prevalence of this disorder has not been fully characterized, it can be associated with debilitating symptoms which severely impact quality of life and can be life-threatening. The underlying pathophysiology of hyperinsulinemic hypoglycemia likely involves a mismatch in the amount of insulin secreted in response to mealtime carbohydrate absorption. It has been observed that the ingestion of a high carbohydrate load often leads to a modest rise in post-prandial glucose levels followed by an inappropriately exaggerated insulin release among individuals with this condition. Low carbohydrate diet sometimes provides full or partial relief of the symptoms.

Standard medical management for RYGB associated postprandial hyperinsulinemic hypoglycemia includes acarbose, which partially reduces carbohydrate absorption from the gut, and diazoxide, which directly inhibits insulin release from pancreatic beta cells. However, the medical options are not reliably effective, leading some individuals to reverse RYGB, which also may not be effective, or even undergo partial pancreatectomy, risking additional complications such as diabetes. Much more reliably effective treatments are needed for this special population who develop this bariatric surgical complication.

Potential mechanisms contributing to the mismatched insulin secretion post RYGB include decreased systemic and adipose tissue inflammation, and increased insulin receptor expression in liver and skeletal muscle, and increases in adiponectin.

Conditions

Hyperinsulinemic Hypoglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm 1: Exenatide (5mcg) + Acarbose Placebo

Exenatide (5 mcg) 30 minutes before the high-carb meal is delivered and acarbose placebo immediately prior to the high-carb meal

Group Type: ACTIVE_COMPARATOR

Exenatide

Intervention Type: DRUG

Exenatide at a dose of 5 mcg

Acarbose Placebo

Intervention Type: DRUG

Placebo for Acarbose

Arm 2: Exenatide (5mcg) + Acarbose (25mg)

Exenatide (5 mcg) 30 minutes before the high-carb meal is delivered and acarbose (25 mg) immediately prior to the high-carb meal

Group Type: ACTIVE_COMPARATOR

Exenatide

Intervention Type: DRUG

Exenatide at a dose of 5 mcg

Acarbose

Intervention Type: DRUG

Acarbose at a dose of 25 mg

Arm 3: Exenatide Placebo + Acarbose (25mg)

Exenatide placebo 30 minutes before the high-carb meal is delivered and acarbose (25 mg) immediately prior to the high-carb meal

Group Type: PLACEBO_COMPARATOR

Acarbose

Intervention Type: DRUG

Acarbose at a dose of 25 mg

Exenatide Placebo

Intervention Type: DRUG

Placebo for Exenatide

Interventions

Exenatide

Exenatide at a dose of 5 mcg

Intervention Type: DRUG

Acarbose

Acarbose at a dose of 25 mg

Intervention Type: DRUG

Exenatide Placebo

Placebo for Exenatide

Intervention Type: DRUG

Acarbose Placebo

Placebo for Acarbose

Intervention Type: DRUG

Other Intervention Names

Byetta

Eligibility Criteria

Inclusion Criteria

1. must have undergone RYGB and subsequently developed post-prandial hypoglycemia (defined as at least 3 episodes over a six-month period with documented capillary blood sugars [<60 mg/dL with hypoglycemic symptoms). Subjects may also have had a formal mixed meal tolerance test with post meal blood sugar <60 mg/dL.

2. Subjects who otherwise meet the study criteria above with hypoglycemia symptoms but who do not have documented hypoglycemia by plasma measurement may undergo a screening visit to document the requisite levels for consideration into the study.

Exclusion Criteria

1. Chronic or acute diseases of the liver.

2. Chronic or acute diseases of the pancreas (including type 1 diabetes or pancreatitis or a history of pancreatitis). Subjects may have a diagnosis of type 2 diabetes but must no longer require diabetes medication.

3. Chronic or acute diseases of the kidneys.

4. Known malignancies and must not have a family history of medullary thyroid cancer.

5. History of pre-RYGB hypoglycemia symptoms or low documented plasma glucose preoperatively.

6. Pregnant or plans to become pregnant throughout study duration

7. Breastfeeding

8. Medication exclusions in addition to the current use of diabetes medications. Subjects will be excluded if they have previously taken GLP-1 agonists.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shalamar D Sibley, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

1503M65841

Identifier Type: -

Identifier Source: org_study_id