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

Tracey McLaughlin9 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Hyperinsulinemia Hypoglycemia

Interventions

Exendin (9-39)DRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (1)

Stanford University School of Medicine

Stanford, California, United States

Outcomes

Primary Outcomes

Treatment effect on plasma glucose

Magnitude of plasma glucose nadir during repeat OGTT after treatment

Time frame: 0-180 minutes following initiation of oral glucose tolerance test (OGTT) conducted after treatment.

Secondary Outcomes

Treatment effect on symptoms of hypoglycemia

Response rate in symptom score during repeat OGTT after treatment.

Time frame: 0-180 minutes following initiation of OGTT

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.