Primary outcomeMean· 3 hours
Mean Plasma Glucose Area Under the Curve (AUC 0-3h)
| Group | Value (mg*min/dl) | Spread |
|---|---|---|
| Exendin-(9-39) 300pmol/kg/Min Dose | 22,192.5 | 4,784.7 |
| Exendin-(9-39) 500pmol/kg/Min Dose | 25,207.1 | 1,157.5 |
| Vehicle | 21,715.9 | 3,597.8 |
Trial · Interventional
CompletedNot applicableResults postedRegistry dataRole of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia
NCTNCT01162499 (opens ClinicalTrials.gov in a new tab)Other id09-007372
This trial does not test a peptide that PepBank tracks.
- Measures Glucagon, does not give it. It appears in an outcome measure.
Overview
- Status
- Completed
- Phase
- Not applicable
- Enrollment
- 7 participants (actual)
- Sponsor
- Diva De Leon · Other
- Design
- Randomized · Open label (no masking)
- Countries
1 country
United States
- Start
- Apr 2010
- Primary completion
- Dec 2014
- Completion
- Dec 2014
- First posted
- 14 Jul 2010 (estimated)
- Last update posted
- 23 Oct 2017
- Conditions
- Postprandial Hypoglycemia
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
201020112012201320142015
- N/A
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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.
Interventions
- Exendin-(9-39)Drug
- VehicleOther
Arms2
Experimental
Exendin-(9-39) first, then Vehicle
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.
Active comparator
Vehicle first, then Exendin-(9-39)
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.
Primary outcomes1
Outcomes the sponsor listed as primary.
Mean Plasma Glucose Area Under the Curve (AUC 0-3h)
Time frame · 3 hours
Registry description
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.
Secondary outcomes(4)
Mean Plasma Insulin Area Under the Curve (AUC 0-3h)
Time frame · 3 hours
Registry description
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.
Mean Acetaminophen Plasma Concentration Area Under the Curve (AUC 0-3h)
Time frame · 3 hours
Registry description
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.
Peak Plasma Glucagon-like Peptide-1 (GLP-1) Concentration During Infusion
Time frame · 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
Registry description
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.
Peak Glucagon Concentration During Infusion
Time frame · 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
Registry description
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.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(4)
Secondary outcomeMean· 3 hours
Mean Plasma Insulin Area Under the Curve (AUC 0-3h)
| Group | Value (pmol*min/l) | Spread |
|---|---|---|
| Exendin-(9-39) 300pmol/kg/Min Dose | 14,695.85 | 12,662.9 |
| Exendin-(9-39) 500pmol/kg/Min Dose | 9,058.5 | 7,562.7 |
| Vehicle | 19,435.4 | 10,392.6 |
Secondary outcomeMean· 3 hours
Mean Acetaminophen Plasma Concentration Area Under the Curve (AUC 0-3h)
| Group | Value (μg*min/l) | Spread |
|---|---|---|
| Exendin-(9-39) 300pmol/kg/Min Dose | 3,387.5 | 898 |
| Exendin-(9-39) 500pmol/kg/Min Dose | 3,742.8 | 124.3 |
| Vehicle | 3,436.6 | 465.2 |
Secondary outcomeMean· 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 Plasma Glucagon-like Peptide-1 (GLP-1) Concentration During Infusion
| Group | Value (pmol/l) | Spread |
|---|---|---|
| Exendin-(9-39) 300pmol/kg/Min Dose | 65.8 | 33.3 |
| Exendin-(9-39) 500pmol/kg/Min Dose | 75.2 | 5.8 |
| Vehicle | 72.8 | 26.1 |
Secondary outcomeMean· 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
| Group | Value (pg/ml) | Spread |
|---|---|---|
| Exendin-(9-39) 300pmol/kg/Min Dose | 127.5 | 75.7 |
| Exendin-(9-39) 500pmol/kg/Min Dose | 145.7 | 33.6 |
| Vehicle | 114.0 | 50.1 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Exendin-(9-39) 300pmol/kg/Min DoseAfter an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 300pmol/kg/min, infused over 4 total hours. | – | 0 / 3 | 0 / 3 |
| Exendin-(9-39) 500pmol/kg/Min DoseAfter an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 500pmol/kg/min, infused over 4 total hours. | – | 0 / 3 | 0 / 3 |
| VehicleAfter an overnight fast, an intravenous (IV) infusion of normal saline (vehicle) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The vehicle was infused over 4 total hours. | – | 0 / 6 | 2 / 6 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies0
Studies that cite this trial.
No study cites this trial.
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 6 Months up to 18 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
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
PepBank is a research reference. Talk to a doctor before you use any peptide.