Role of Nutrient Transit in Hyperinsulinemic Hypoglycemia

Role of Nutrient Transit and Incretin Hormones in Hyperinsulinemic Hypoglycemia

Severe hypoglycemia (low blood sugar)after gastric bypass surgery is an increasingly recognized condition, characterized by symptoms of hypoglycemia after eating and inappropriately elevated insulin concentrations that occur at the time of hypoglycemia. Severe hypoglycemia can be dangerous and debilitating and can also impact cognitive function. At the moment no medical therapies have been developed for this disorder. Determining why some but not other patients develop this condition would allow for improved prediction, prevention, and treatment approaches. The purpose of the study is to understand the physiological changes observed in those patients who undergo gastric bypass and develop symptomatic hypoglycemia.

Study Overview

• Status: Recruiting
• Conditions: Post-Bariatric Hypoglycemia
• Intervention / Treatment: Behavioral: Use of Continuous Glucose Monitor (CGM); Other: Use of "Cardea Solo" monitoring

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305-5103
      • Recruiting
      • Stanford University School of Medicine
      • Contact: Colleen Craig, MD; Phone Number: 650-724-2474; Email: cmcraig@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female patients 18-70 years of age
• Post-bariatric surgery more than 6 months prior to signing the informed consent (not required for non-surgical controls)
• Documented history of hyperinsulinemic hypoglycemia (not required for post-bariatric and non-surgical controls)

Exclusion Criteria:

• Patients currently using sulfonylureas or other medications that may interfere with glucose metabolism within 5 half-lives of drug.
• Participation in any clinical investigation within 4 weeks prior to dosing
• History of or current insulinoma
• Active infection or significant acute illness within 2 weeks prior to dosing
• Female patients who are pregnant or lactating
• Women of childbearing potential and not utilizing effective contraceptive methods
• Inadequate end organ function as defined by: Serum creatinine >2.0 mg/dL, alanine transaminase (ALT) and aspartate aminotransferase (AST) > 2 x Upper Normal Limit
• Allergy to test meal or medications used in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remote Phase: Post-Bariatric Hypoglycemia Patients; Participants will wear continuous glucose monitor (CGM) in a blinded manner (cannot see data output) for 20 days followed by in an unblinded manner (can see data output) for 20 days.	Behavioral: Use of Continuous Glucose Monitor (CGM); Participants will wear CGM; Other: Use of "Cardea Solo" monitoring; Participants will wear a "Cardea Solo" patch during blinded CGM use
No Intervention: In-Clinic Phase: Post-Bariatric Hypoglycemia Patients; Participants will attend 1-3 study visits over the period of approximately 2 months, with metabolic parameters assessed under a variety of conditions. This group will also wear CGM during a portion of the metabolic tests. This may include participants from the Remote Phase or newly enrolled participants.
No Intervention: In-Clinic Phase: Surgical Controls; Participants will attend 1-3 study visits over the period of approximately 2 months, with metabolic parameters assessed under a variety of conditions.
No Intervention: In-Clinic Phase: Nonsurgical Controls; Participants will attend 1-3 study visits over the period of approximately 2 months, with metabolic parameters assessed under a variety of conditions.
No Intervention: In-Clinic Phase: Post-Bariatric Hypoglycemia Patients with indwelling gastrostomy tube; Participants will undergo standardized mixed meal tolerance tests via oral, gastrostomy tube, and concomitant oral + gastrostomy tube routes of delivery with metabolic parameters assessed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steady state plasma glucose (SSPG) as a measure of insulin sensitivity	This endpoint applies to the In-Clinic Phase cohorts: Post-Bariatric Hypoglycemia, Surgical Controls, Non-Surgical Controls. This is a one day in-person appointment lasting approximately 6 hours.	Baseline 4-hour SSPG
Rate of gastric emptying	This endpoint applies to the In-Clinic Phase cohorts: Post-Bariatric Hypoglycemia, Surgical Controls, Non-Surgical Controls. This is an in-person appointment lasting approximately 5 hours.	Baseline 4-hour scintigraphy procedure
Concentration of Glucagon-Like peptide 1 secretion augmentation of insulin secretion rate	This endpoint applies to the In-Clinic Phase cohorts: Post-Bariatric Hypoglycemia, Surgical Controls, Non-Surgical Controls. The blood collected from the SSPG will be stored and analyzed for the concentration of GLP-1 at multiple timepoints.	Baseline 4-hour graded-glucose infusion
Rate of clinically important hypoglycemia (Level 2 hypoglycemia, <54 mg/dL)	This endpoint applies to Remote Phase participants	40 days
Percent time in clinically important hypoglycemia (Level 2 hypoglycemia, <54 mg/dL)	This endpoint applies to Remote Phase participants	40 days
Rate of arrhythmia during hypoglycemia	This endpoint applies to Remote Phase participants	10 days

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: American Diabetes Association
• Investigators: Principal Investigator: Tracey McLaughlin, MD, Stanford University; Study Director: Colleen Craig, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2020
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: October 29, 2020
• First Submitted That Met QC Criteria: October 29, 2020
• First Posted (Actual): November 4, 2020

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Infant, Newborn, Diseases; Hyperinsulinism; Pancreatic Diseases; Hypoglycemia; Congenital Hyperinsulinism; Nesidioblastosis
• Other Study ID Numbers: 52254

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No