-A +A
Text Size
Home » Clinical Trials

Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia

This study is currently recruiting participants.
Verified on July 2011 by Children's Hospital of Philadelphia
First Received on May 4, 2010. Last Updated on July 6, 2011
Sponsor:
Children's Hospital of Philadelphia
Information provided by:
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01162499

Purpose
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 GLP-1 secretion in response to a glucose load is increased in children with 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.

Condition Intervention
Postprandial Hypoglycemia Drug: exendin-(9-39) Other: placebo normal saline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science

Official Title: Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia After Nissen Fundoplication: Studies With the GLP-1 Receptor Antagonist Exendin-(9-39)

Further study details as provided by Children's Hospital of Philadelphia:
Primary Outcome Measures:

  • Nadir blood glucose levels [ Time Frame: -60 to 240 minutes ] [ Designated as safety issue: No ]
    Hypoglycemia sometimes occurs without being preceded by hyperglycemia but in association with high insulin levels. GLP-1 stimulated by the rapid emptying of liquid meals into the intestine may be responsible for the exaggerated insulin rise and subsequent hypoglycemia.

Secondary Outcome Measures:

  • Plasma insulin and glucagon levels. [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]
    glucagon will only be obtained in subjects that weight is > or equal to 9kg
  • acetaminophen levels [ Time Frame: samples taken every 30 minutes after ingestion of mixed meal (pediasure/formula) ] [ Designated as safety issue: No ]
    evaluation fo gastric emptying- acetaminophen levels
  • plasma GLP1 [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]
    collection of GLP1 after ingestion of Mixed meal

Estimated Enrollment: 16
Study Start Date: April 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
exendin-(9-39): Experimental IV infusion of exendin-(9-39)for 5 hours Intervention: Drug: exendin-(9-39) Drug: exendin-(9-39) IV infusion of exendin-(9-39)for 5 hours Other Name: exendin-(9-39)
placebo normal saline: Placebo Comparator normal saline Intervention: Other: placebo normal saline Other: placebo normal saline saline infusion for 5 hours at 0.06mL/kg/hr Other Names: placebo normal saline saline infusion

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
Ages Eligible for Study: 6 Months to 18 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

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