Clinical trial NCT01162499: Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia
Official title: Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia After Nissen Fundoplication: Studies With the GLP-1 Receptor Antagonist Exendin-(9-39)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postprandial Hypoglycemia
Keywords: Post prandial hypoglycemia
hypoglycemia
Nissen fundoplication
Dumping
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Lester and Liesel Baker Foundation
First posted: 2010-07-14
Enrollment: 7
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: It has been proposed that the rapid gastric emptying of carbohydrate containing fluids into the intestine causes hyperglycemia followed by reactive hypoglycemia. The investigators have shown that glucagon-like peptide-1 (GLP-1) secretion in response to a glucose load is increased in children with Post-prandial hypoglycemia (PPH). This is a proof of concept study to investigate the causative role of GLP-1 in the pathophysiology of PPH after fundoplication by evaluating the effects of GLP-1 receptor antagonism on metabolic variables after a mixed meal.

Hypothesis: In children with post-prandial hypoglycemia after fundoplication, antagonism of the GLP-1 receptor by exendin-(9-39) will elevate nadir blood glucose levels after a meal challenge and prevent post-prandial hypoglycemia.

Detailed description: PPH is a frequent complication of fundoplication in children. The mechanism responsible for the PPH is poorly understood, but involves an exaggerated insulin response to a meal and subsequent hypoglycemia. We have shown that children with PPH after Nissen fundoplication have abnormally exaggerated secretion of GLP-1, an incretin hormone with multiple glucose lowering effects including stimulation of insulin secretion and suppression of glucagon secretion. In this study we seek to examine the causal role of endogenous GLP-1 in PPH after fundoplication by evaluating the effects of antagonizing the GLP-1 receptor with exendin-(9-39) on key metabolic features of PPH.

Eligibility criteria: Inclusion Criteria:

* Children (6 months-18 years) who have had fundoplication or other gastric surgeries, irrespective of duration of postoperative period
* Weight \> 6.5 Kg
* Signs and/or symptoms of PPH: post-prandial blood glucose levels of \< 70 mg/dL ; symptoms including but not limited to feeding difficulties, irritability, nausea, diarrhea, pallor, diaphoresis, weakness, and lethargy after meals

Exclusion Criteria:

* Evidence of a medical condition that might alter results or compromise the elimination of the peptide, including, but not limited to: active infection, kidney failure (creatinine ≥ 2x above upper limit for age), severe liver dysfunction (AST or ALT ≥ 5x upper limit of normal for AST or ALT), severe respiratory or cardiac failure
* Other disorders of glucose regulation such as diabetes mellitus, congenital hyperinsulinism, glycogen storage disease
* Current use (within 1 week) of medications that may alter glucose homeostasis such as glucocorticoids, diazoxide, octreotide
* Use of antihistaminics within 10 days prior to the study
* Moderate and severe anemia defined as a hemoglobin \< 10g/dL
* Pregnancy
* Milk and soy protein allergy

Primary outcomes:
measure: Mean Plasma Glucose Area Under the Curve (AUC 0-3h)
timeFrame: 3 hours
Secondary outcomes:
measure: Mean Plasma Insulin Area Under the Curve (AUC 0-3h)
timeFrame: 3 hours
measure: Mean Acetaminophen Plasma Concentration Area Under the Curve (AUC 0-3h)
timeFrame: 3 hours
measure: Peak Plasma Glucagon-like Peptide-1 (GLP-1) Concentration During Infusion
timeFrame: 60 minutes before the start of the infusion, again at the start of the infusion (time 0), and then every 30 minutes until 3 hours after the start of the infusion
measure: Peak Glucagon Concentration During Infusion
timeFrame: 60 minutes before the start of the infusion, again at the start of the infusion (time 0), and then every 30 minutes until 3 hours after the start of the infusion
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Diva De Leon, MD
role: PRINCIPAL_INVESTIGATOR
References: