Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia

NCT01162499 | Completed Results

• 1 other identifier: 09-007372
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Postprandial Hypoglycemia

Keywords

Post prandial hypoglycemia; hypoglycemia; Nissen fundoplication; Dumping

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Mean Plasma Insulin Area Under the Curve (AUC 0-3h)

  3 hours

• Mean Acetaminophen Plasma Concentration Area Under the Curve (AUC 0-3h)

  3 hours

• Peak Plasma Glucagon-like Peptide-1 (GLP-1) Concentration During 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

• Peak Glucagon Concentration During 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

Study Arms (2)

Exendin-(9-39) first, then Vehicle

EXPERIMENTAL

After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) will be started 1 hour prior to the meal challenge and continued for 5 hours. After the first hour of the infusion, subjects will undergo a mixed meal tolerance test in which Pediasure (10cc/kg) will be consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes (for infants under 12 months, Pediasure will be replaced by the infant's formula). Blood samples will be drawn at different time points during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose for the first 3 subjects will be 300pmol/kg/min and, if tolerated, the dose will be increased to 500pmol/kg/min for subsequent subjects. The next day, all procedures will be repeated except subjects will receive an IV infusion of normal saline (vehicle) over 6 hours.

Drug: Exendin-(9-39); Other: Vehicle

Vehicle first, then Exendin-(9-39)

ACTIVE COMPARATOR

After an overnight fast, an intravenous (IV) infusion of normal saline (vehicle) will be started 1 hour prior to the meal challenge and continued for 5 hours. After the first hour of the infusion, subjects will undergo a mixed meal tolerance test in which Pediasure (10cc/kg) will be consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes (for infants under 12 months, Pediasure will be replaced by the infant's formula). Blood samples will be drawn at different time points during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The next day, all procedures will be repeated except subjects will receive an IV infusion of Exendin-(9-39) which will be started 1 hour prior to the meal challenge and continue for 5 hours. The dose for the first 3 subjects will be 300pmol/kg/min and, if tolerated, the dose will be increased to 500pmol/kg/min for subsequent subjects.

Drug: Exendin-(9-39); Other: Vehicle

Interventions

Exendin-(9-39) DRUG

IV infusion of exendin-(9-39) for 5 hours

Exendin-(9-39) first, then Vehicle; Vehicle first, then Exendin-(9-39)

Vehicle OTHER

Normal saline (vehicle) infusion for 5 hours at 0.06 mL/kg/hr

Also known as: Normal Saline

Exendin-(9-39) first, then Vehicle; Vehicle first, then Exendin-(9-39)

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Diva De Leon: lead
• Lester and Liesel Baker Foundation: collaborator

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Hypoglycemia

Interventions

exendin (9-39); Saline Solution

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

The primary limitation in addition to small sample size, relates to the fact that none of the subjects experienced significant hypoglycemia during the 3 hour post-meal period.

Results Point of Contact

• Title: Diva De Leon, MD
• Organization: Children's Hospital of Philadelphia

DELEON@email.chop.edu

267-426-5529

Study Officials

• Diva De Leon, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D. Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: May 4, 2010
• First Posted: July 14, 2010
• Study Start: April 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: October 23, 2017
• Results First Posted: November 9, 2016

Record last verified: 2017-09

Locations

US (1)