Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia
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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 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) |
- blood glucose levels [ Time Frame: 0-240 min ] [ Designated as safety issue: No ]
- 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: | January 2014 |
| Estimated Primary Completion Date: | January 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 0.06mL/kg/hr
Other Names:
|
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 |
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| Contact: Stephanie Givler, BS,CCRC | 267-426-7622 | givler@email.chop.edu |
| United States, Pennsylvania | |
| The Children's Hospital of Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Principal Investigator: Diva De Leon, MD | |
| Sub-Investigator: Andrew Calabria, MD | |
| 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: | September 25, 2012 |
| 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 Hormones |
Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Gastrointestinal Agents Therapeutic Uses Incretins |
ClinicalTrials.gov processed this record on May 21, 2013