Evaluation of Single Ascending Doses of Subcutaneous Exendin 9-39 in Patients With Post-Bariatric Hypoglycemia

Subcutaneous Injection of Exendin (9-39) in Subjects With Hyperinsulinemic Hypoglycemia Post-Bariatric Surgery

This study is designed to evaluate the safety, efficacy, and pharmacokinetic profile of single ascending doses of exendin 9-39 administered by subcutaneous route in subjects with post-bariatric hypoglycemia.

Study Overview

• Status: Unknown
• Conditions: Hyperinsulinemia Hypoglycemia
• Intervention / Treatment: Drug: Exendin (9-39)

Detailed Description

Post-Bariatric Hypoglycemia (PBH) is a debilitating rare disease afflicting 0.2-6.9% of post-bariatric patients, characterized by repeated severe hypoglycemic episodes with neuroglycopenic symptoms and marked disability. There are no effective medical therapies.

While the cause is not known, exaggerated postprandial secretion of glucagon-like peptide-1 (GLP-1) as a result of altered nutrient transit likely plays a major role. GLP-1 is an incretin hormone secreted primarily by the distal ileum that contributes to postprandial glucose regulation. Exendin 9-39 (Ex9) is a specific GLP-1 receptor antagonist, that when given via continuous IV infusion, has been shown to effectively prevent postprandial hypoglycemia in patients with PBH. Subcutaneous (SC) injection of Ex9 may represent a safe, effective and practical therapeutic approach to treating PBH.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Post-bariatric surgery more than 6 months prior to signing the informed consent
• Reported history of Whipple's triad: the occurrence of hypoglycemic symptoms associated with blood glucose of ≤55 mg/dL, and resolution with glucose or carbohydrate administration.
• Symptomatic hypoglycemia during the baseline/screening OGTT, as defined by the presence of plasma glucose ≤55 mg/dL with concomitant autonomic and/or neuroglycopenic symptoms.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dose A; Subcutaneous injection of Dose A of Exendin (9-39)	Drug: Exendin (9-39)
Active Comparator: Dose B; Subcutaneous injection of Dose B of Exendin (9-39)	Drug: Exendin (9-39)
Active Comparator: Dose C; Subcutaneous injection of Dose C of Exendin (9-39)	Drug: Exendin (9-39)
Active Comparator: Dose D; Subcutaneous injection of Dose D of Exendin (9-39)	Drug: Exendin (9-39)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment effect on plasma glucose	Magnitude of plasma glucose nadir during repeat OGTT after treatment	0-180 minutes following initiation of oral glucose tolerance test (OGTT) conducted after treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment effect on symptoms of hypoglycemia	Response rate in symptom score during repeat OGTT after treatment.	0-180 minutes following initiation of OGTT

Collaborators and Investigators

• Sponsor: Tracey McLaughlin

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): May 1, 2016
• Study Completion (Anticipated): May 1, 2017

Study Registration Dates

• First Submitted: December 15, 2016
• First Submitted That Met QC Criteria: December 15, 2016
• First Posted (Estimate): December 19, 2016

Study Record Updates

• Last Update Posted (Estimate): December 19, 2016
• Last Update Submitted That Met QC Criteria: December 15, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Post-bariatric hypoglycemia; Non-insulinoma pancreatogenous hypoglycemia syndrome; Late dumping syndrome
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Hyperinsulinism
• Other Study ID Numbers: 34054

Plan for Individual participant data (IPD)

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