Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Diva De Leon, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01162499
First received: May 4, 2010
Last updated: July 30, 2014
Last verified: July 2014
  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 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


Estimated Enrollment: 16
Study Start Date: April 2010
Estimated Study Completion Date: December 2014
Estimated 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
Other Name: exendin-(9-39)
Placebo Comparator: placebo normal saline
normal saline
Other: placebo normal saline
saline infusion for 5 hours at 0.06 mL/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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01162499

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

No publications provided

Responsible Party: Diva De Leon, M.D. Assistant Professor of Pediatrics, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01162499     History of Changes
Other Study ID Numbers: 09-007372
Study First Received: May 4, 2010
Last Updated: July 30, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Glucagon
Glucagon-Like Peptide 1
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Incretins

ClinicalTrials.gov processed this record on August 27, 2014