Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia

Hyperinsulinemic Hypoglycemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02685852
• Other study ID #: 1503M65841
• Status: Completed
• Phase: Phase 1
• Start date: February 2016
• Est. completion date: July 22, 2019

Study information

• Verified date: April 2021
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: July 22, 2019
• Est. primary completion date: July 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Congenital Hyperinsulinism
• Hyperinsulinemic Hypoglycemia
• Hypoglycemia

Intervention

Drug:
• Exenatide
Exenatide at a dose of 5 mcg
• Acarbose
Acarbose at a dose of 25 mg
• Exenatide Placebo
Placebo for Exenatide
• Acarbose Placebo
Placebo for Acarbose

Locations

Country	Name	City	State
United States	University of Minnesota Medical Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	During the 4-hour test period
Primary	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	15, 30, 45, 60, 90, 120, 180 and 240 minutes
Secondary	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).	post meal test
Secondary	Change in post-prandial blood glucose from 0min to 120min	% change in blood glucose 0min to 120min	0min to 120min
Secondary	Change in post-prandial Insulin levels (mcg/mL)	% change in insulin 0min to 120min	0min to 120min