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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01162499
Other study ID # 09-007372
Secondary ID
Status Completed
Phase N/A
First received May 4, 2010
Last updated September 21, 2017
Start date April 2010
Est. completion date December 2014

Study information

Verified date September 2017
Source Children's Hospital of Philadelphia
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 7
Est. completion date December 2014
Est. primary completion date December 2014
Accepts healthy volunteers No
Gender All
Age group 6 Months to 18 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Exendin-(9-39)
IV infusion of exendin-(9-39) for 5 hours
Other:
Vehicle
Normal saline (vehicle) infusion for 5 hours at 0.06 mL/kg/hr

Locations

Country Name City State
United States The Children's Hospital of Philadelphia Philadelphia Pennsylvania

Sponsors (2)

Lead Sponsor Collaborator
Diva De Leon Lester and Liesel Baker Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Mean Plasma Glucose Area Under the Curve (AUC 0-3h) To examine the effect of Exendin-(9-39) on plasma glucose levels samples were collected at various time points before and during the infusion [Exendin-(9-39) or vehicle] including: 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 meal. Using this information, the mean plasma glucose area under the curve (AUC) from the start of the infusion to the end of the infusion (3 hours) was calculated for both doses of Exendin-(9-39) [300pmol/kg/min & 500pmol/kg/min] and compared with the vehicle. 3 hours
Secondary Mean Plasma Insulin Area Under the Curve (AUC 0-3h) To examine the effect of Exendin-(9-39) on plasma insulin levels, samples were collected at various time points before and during the infusion [Exendin-(9-39) or vehicle] including: 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 meal. Using this information, the mean plasma insulin area under the curve (AUC) from the start of the infusion to the end of the infusion (3 hours) was calculated for both doses of Exendin-(9-39) [300pmol/kg/min & 500pmol/kg/min] and compared with the vehicle. 3 hours
Secondary Mean Acetaminophen Plasma Concentration Area Under the Curve (AUC 0-3h) The effect of gastric emptying was examined using the acetaminophen method whereby acetaminophen (30mg/kg or maximum of 1500mg) was mixed into the Pediasure/formula during the meal tolerance testing. Blood samples were collected every 30 minutes and the absorption of acetaminophen was determined by the gastric emptying rate, as the serum concentrations correlate with gastric emptying of liquids. Mean acetaminophen levels for each group at each time point were used to calculate the Area Under the Concentration versus Time Curve (AUC expressed in µg*min/l) after the consumption of formula for each of the two Exendin-(9-39) dose levels and normal saline vehicle. 3 hours
Secondary Peak Plasma Glucagon-like Peptide-1 (GLP-1) Concentration During Infusion To examine the effect of Exendin-(9-39) on plasma glucagon-like peptide-1 levels, samples were collected at various time points before and during the infusion [Exendin-(9-39) or vehicle] including: 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. The mean peak glucagon-like peptide-1 concentration for both Exendin-(9-39) doses were compared with the peak glucagon-like peptide-1 during vehicle infusion. 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
Secondary Peak Glucagon Concentration During Infusion To examine the effect of Exendin-(9-39) on plasma glucagon levels, samples were collected at various 3 hours after the start of the infusion. The mean peak glucagon concentration for both Exendin-(9-39) doses were compared with the peak glucagon during vehicle infusion. 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
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