Clinical trial NCT02996812: Evaluation of Single Ascending Doses of Subcutaneous Exendin 9-39 in Patients With Post-Bariatric Hypoglycemia
Official title: Subcutaneous Injection of Exendin (9-39) in Subjects With Hyperinsulinemic Hypoglycemia Post-Bariatric Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hyperinsulinemia Hypoglycemia
Keywords: Post-bariatric hypoglycemia
Non-insulinoma pancreatogenous hypoglycemia syndrome
Late dumping syndrome
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2016-12-19
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment effect on plasma glucose
timeFrame: 0-180 minutes following initiation of oral glucose tolerance test (OGTT) conducted after treatment.
Secondary outcomes:
measure: Treatment effect on symptoms of hypoglycemia
timeFrame: 0-180 minutes following initiation of OGTT
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Tracey McLaughlin, MD
role: PRINCIPAL_INVESTIGATOR
References: