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Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia

This study has been completed.
Information provided by (Responsible Party):
Diva De Leon, Children's Hospital of Philadelphia Identifier:
First received: May 4, 2010
Last updated: March 12, 2015
Last verified: March 2015

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.

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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia After Nissen Fundoplication: Studies With the GLP-1 Receptor Antagonist Exendin-(9-39)

Resource links provided by NLM:

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

Primary Outcome Measures:
  • blood glucose levels [ Time Frame: 0-240 min ] [ Designated as safety issue: No ]

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 glucagon-like peptide-1 (GLP1) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]
    collection of GLP1 after ingestion of Mixed meal

Enrollment: 7
Study Start Date: April 2010
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: exendin-(9-39)
IV infusion of exendin-(9-39)for 5 hours
Drug: exendin-(9-39)
IV infusion of exendin-(9-39)for 5 hours
Placebo Comparator: placebo normal saline
normal saline
Other: placebo normal saline
saline infusion for 5 hours at 0.06 mL/kg/hr
Other Name: 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.

Ages Eligible for Study:   6 Months to 18 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT01162499

United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Diva De Leon
Principal Investigator: Diva De Leon, MD Children's Hospital of Philadelphia
  More Information

Responsible Party: Diva De Leon, M.D. Assistant Professor of Pediatrics, Children's Hospital of Philadelphia Identifier: NCT01162499     History of Changes
Other Study ID Numbers: 09-007372 
Study First Received: May 4, 2010
Last Updated: March 12, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital of Philadelphia:
Post prandial hypoglycemia
Nissen fundoplication

Additional relevant MeSH terms:
Glucose Metabolism Disorders
Metabolic Diseases
Glucagon-Like Peptide 1
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Incretins processed this record on October 28, 2016