Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia

April 30, 2021 updated by: University of Minnesota

A Pilot Study Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia Post-RYGB

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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
Exenatide at a dose of 5 mcg
Other Names:
  • Byetta
Placebo for Acarbose
Active Comparator: 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
Exenatide at a dose of 5 mcg
Other Names:
  • Byetta
Acarbose at a dose of 25 mg
Placebo Comparator: 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
Acarbose at a dose of 25 mg
Placebo for Exenatide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glucose area under the curve (AUC) following treatment for each 4-hour test period
Time Frame: During the 4-hour test period
Each time point (15, 30, 45, 60, 90, 120, 180 and 240 minutes) will be used to calculate AUC using the trapezoidal method.
During the 4-hour test period
Presence of hypoglycemia
Time Frame: 15, 30, 45, 60, 90, 120, 180 and 240 minutes
If at each time-point (15, 30, 45, 60, 90, 120, 180 and 240 minutes) plasma glucose is <60 mg/dL, participants will be defined as hypoglycemic
15, 30, 45, 60, 90, 120, 180 and 240 minutes

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minimum post-prandial blood sugar level (mg/dL)
Time Frame: post meal test
The lowest post-prandial blood glucose level at any time point (15, 30, 45, 60, 90, 120, 180 and 240 minutes) may be used as the minimum post-prandial blood sugar level (mg/dL).
post meal test
Change in post-prandial blood glucose from 0min to 120min
Time Frame: 0min to 120min
% change in blood glucose 0min to 120min
0min to 120min
Change in post-prandial Insulin levels (mcg/mL)
Time Frame: 0min to 120min
% change in insulin 0min to 120min
0min to 120min

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Shalamar D Sibley, MD, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Actual)

July 22, 2019

Study Completion (Actual)

July 22, 2019

Study Registration Dates

First Submitted

January 19, 2016

First Submitted That Met QC Criteria

February 15, 2016

First Posted (Estimate)

February 19, 2016

Study Record Updates

Last Update Posted (Actual)

May 6, 2021

Last Update Submitted That Met QC Criteria

April 30, 2021

Last Verified

April 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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