Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02685852
Recruitment Status : Completed
First Posted : February 19, 2016
Last Update Posted : July 22, 2019
Sponsor:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

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.

Condition or disease Intervention/treatment Phase
Hyperinsulinemic Hypoglycemia Drug: Exenatide Drug: Acarbose Drug: Placebo Phase 1

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Pilot Study Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia Post-RYGB
Study Start Date : February 2016
Actual Primary Completion Date : July 10, 2019
Actual Study Completion Date : July 10, 2019


Arm Intervention/treatment
Active Comparator: Arm 1: Exenatide (5mcg)
Exenatide at a dose of 5 mcg
Drug: Exenatide
Exenatide at a dose of 5 mcg
Other Name: Byetta

Active Comparator: Arm 2: Exenatide (5mcg) + Acarbose (25mg)
Exenatide (5mcg) + Acarbose (25mg)
Drug: Exenatide
Exenatide at a dose of 5 mcg
Other Name: Byetta

Drug: Acarbose
Acarbose at a dose of 25 mg

Placebo Comparator: Arm 3: Placebo
Placebo
Drug: Placebo
Placebo




Primary Outcome Measures :
  1. 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.

  2. 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


Secondary Outcome Measures :
  1. 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).

  2. Change in post-prandial blood glucose from 0min to 120min [ Time Frame: 0min to 120min ]
    % change in blood glucose 0min to 120min

  3. Change in post-prandial Insulin levels (mcg/mL) [ Time Frame: 0min to 120min ]
    % change in insulin 0min to 120min



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02685852


Locations
Layout table for location information
United States, Minnesota
University of Minnesota Medical Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Layout table for investigator information
Principal Investigator: Shalamar D Sibley, MD University of Minnesota - Clinical and Translational Science Institute

Layout table for additonal information
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT02685852     History of Changes
Other Study ID Numbers: 1503M65841
First Posted: February 19, 2016    Key Record Dates
Last Update Posted: July 22, 2019
Last Verified: July 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Congenital Hyperinsulinism
Hyperinsulinism
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Infant, Newborn, Diseases
Exenatide
Acarbose
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Glycoside Hydrolase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action