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

Hyperinsulinemia Hypoglycemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02996812
• Other study ID #: 34054
• Status: Active, not recruiting
• Phase: Phase 1
• First received: December 15, 2016
• Last updated: December 15, 2016
• Start date: April 2015
• Est. completion date: May 2017

Study information

• Verified date: December 2016
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 9
• Est. completion date: May 2017
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyperinsulinemia Hypoglycemia
• Hyperinsulinism
• Hypoglycemia

Intervention

Drug:
• Exendin (9-39)

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Tracey McLaughlin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	Treatment effect on symptoms of hypoglycemia	Response rate in symptom score during repeat OGTT after treatment.	0-180 minutes following initiation of OGTT	No