Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia
Primary Purpose
Hyperinsulinemic Hypoglycemia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Exenatide
Acarbose
Exenatide Placebo
Acarbose Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hyperinsulinemic Hypoglycemia
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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:
- Chronic or acute diseases of the liver.
- 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.
- Chronic or acute diseases of the kidneys.
- Known malignancies and must not have a family history of medullary thyroid cancer.
- History of pre-RYGB hypoglycemia symptoms or low documented plasma glucose preoperatively.
- Pregnant or plans to become pregnant throughout study duration
- Breastfeeding
- Medication exclusions in addition to the current use of diabetes medications. Subjects will be excluded if they have previously taken GLP-1 agonists.
Sites / Locations
- University of Minnesota Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Arm 1: Exenatide (5mcg) + Acarbose Placebo
Arm 2: Exenatide (5mcg) + Acarbose (25mg)
Arm 3: Exenatide Placebo + Acarbose (25mg)
Arm Description
Exenatide (5 mcg) 30 minutes before the high-carb meal is delivered and acarbose placebo immediately prior to the high-carb meal
Exenatide (5 mcg) 30 minutes before the high-carb meal is delivered and acarbose (25 mg) immediately prior to the high-carb meal
Exenatide placebo 30 minutes before the high-carb meal is delivered and acarbose (25 mg) immediately prior to the high-carb meal
Outcomes
Primary Outcome Measures
Glucose area under the curve (AUC) following treatment for each 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.
Presence of hypoglycemia
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
Secondary Outcome Measures
Minimum post-prandial blood sugar level (mg/dL)
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).
Change in post-prandial blood glucose from 0min to 120min
% change in blood glucose 0min to 120min
Change in post-prandial Insulin levels (mcg/mL)
% change in insulin 0min to 120min
Full Information
NCT ID
NCT02685852
First Posted
January 19, 2016
Last Updated
April 30, 2021
Sponsor
University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT02685852
Brief Title
Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia
Official Title
A Pilot Study Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia Post-RYGB
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
February 2016 (undefined)
Primary Completion Date
July 22, 2019 (Actual)
Study Completion Date
July 22, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperinsulinemic Hypoglycemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: Exenatide (5mcg) + Acarbose Placebo
Arm Type
Active Comparator
Arm Description
Exenatide (5 mcg) 30 minutes before the high-carb meal is delivered and acarbose placebo immediately prior to the high-carb meal
Arm Title
Arm 2: Exenatide (5mcg) + Acarbose (25mg)
Arm Type
Active Comparator
Arm Description
Exenatide (5 mcg) 30 minutes before the high-carb meal is delivered and acarbose (25 mg) immediately prior to the high-carb meal
Arm Title
Arm 3: Exenatide Placebo + Acarbose (25mg)
Arm Type
Placebo Comparator
Arm Description
Exenatide placebo 30 minutes before the high-carb meal is delivered and acarbose (25 mg) immediately prior to the high-carb meal
Intervention Type
Drug
Intervention Name(s)
Exenatide
Other Intervention Name(s)
Byetta
Intervention Description
Exenatide at a dose of 5 mcg
Intervention Type
Drug
Intervention Name(s)
Acarbose
Intervention Description
Acarbose at a dose of 25 mg
Intervention Type
Drug
Intervention Name(s)
Exenatide Placebo
Intervention Description
Placebo for Exenatide
Intervention Type
Drug
Intervention Name(s)
Acarbose Placebo
Intervention Description
Placebo for Acarbose
Primary Outcome Measure Information:
Title
Glucose area under the curve (AUC) following treatment for each 4-hour test period
Description
Each time point (15, 30, 45, 60, 90, 120, 180 and 240 minutes) will be used to calculate AUC using the trapezoidal method.
Time Frame
During the 4-hour test period
Title
Presence of hypoglycemia
Description
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
Time Frame
15, 30, 45, 60, 90, 120, 180 and 240 minutes
Secondary Outcome Measure Information:
Title
Minimum post-prandial blood sugar level (mg/dL)
Description
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).
Time Frame
post meal test
Title
Change in post-prandial blood glucose from 0min to 120min
Description
% change in blood glucose 0min to 120min
Time Frame
0min to 120min
Title
Change in post-prandial Insulin levels (mcg/mL)
Description
% change in insulin 0min to 120min
Time Frame
0min to 120min
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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:
Chronic or acute diseases of the liver.
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.
Chronic or acute diseases of the kidneys.
Known malignancies and must not have a family history of medullary thyroid cancer.
History of pre-RYGB hypoglycemia symptoms or low documented plasma glucose preoperatively.
Pregnant or plans to become pregnant throughout study duration
Breastfeeding
Medication exclusions in addition to the current use of diabetes medications. Subjects will be excluded if they have previously taken GLP-1 agonists.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shalamar D Sibley, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia
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