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Trial record 26 of 748 for:    Area Under Curve AND meal

Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia

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ClinicalTrials.gov Identifier: NCT01162499
Recruitment Status : Completed
First Posted : July 14, 2010
Results First Posted : November 9, 2016
Last Update Posted : October 23, 2017
Sponsor:
Collaborator:
Lester and Liesel Baker Foundation
Information provided by (Responsible Party):
Diva De Leon, Children's Hospital of Philadelphia

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Postprandial Hypoglycemia
Interventions Drug: Exendin-(9-39)
Other: Vehicle
Enrollment 7
Recruitment Details Children were recruited from the Division of Endocrinology and Diabetes at The Children's Hospital of Philadelphia.
Pre-assignment Details One subject signed consent but they were excluded from study participation after the study team was unable to establish IV access.
Arm/Group Title Exendin-(9-39) First, Then Vehicle Vehicle First, Then Exendin-(9-39)
Hide Arm/Group Description After 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 for the first 3 subjects was 300pmol/kg/min and, as planned, it was increased to 500pmol/kg/min for subsequent subjects. The next day, all procedures were repeated except subjects received an IV infusion of normal saline (vehicle) over 4 hours. After 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 to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The next day, all procedures were repeated except subjects received an IV infusion of Exendin-(9-39) which was started 1 hour prior to the meal challenge and continued for 4 hours. The dose for the first 3 subjects was 300pmol/kg/min and, as planned, it was increased to 500pmol/kg/min for subsequent subjects.
Period Title: Intervention 1 (4 Hours)
Started 3 4
Received Intervention 3 3
Completed 3 3
Not Completed 0 1
Reason Not Completed
Unable to establish IV access             0             1
Period Title: Intervention 2 (4 Hours)
Started 3 3
Completed 3 3
Not Completed 0 0
Arm/Group Title Subject Population
Hide Arm/Group Description All subjects enrolled and treated in the protocol served as their own control. Because of this and the small sample size, baseline characteristic data is presented together.
Overall Number of Baseline Participants 6
Hide Baseline Analysis Population Description
Baseline analysis population includes all subjects who were randomized and began treatment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
<=18 years
6
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
Female
1
  16.7%
Male
5
  83.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
6
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants
6
Previous Surgery  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants
Nissen fundoplication 5
Gastric pull-through 1
Feeding Regimen  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants
Oral Only 2
Both Oral & Gastrostomy 3
Gastrostomy Only 1
Post-Prandial Hypoglycemia Treatment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants
Acarbose 4
Feeding 2
[1]
Measure Description: Subjects with feeding manipulations had feedings which were modified to decrease volume and slow the rate of delivery.
Post-Prandial Hypoglycemia Treatment Frequency  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants
Intermittent 3
Frequent 3
Age at Post-Prandial Hypoglycemia Diagnosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants
Less than 1 year 1
Between 1-2 years 1
Between 2-3 years 1
Between 3-4 years 3
1.Primary Outcome
Title Mean Plasma Glucose Area Under the Curve (AUC 0-3h)
Hide 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.
Time Frame 3 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Changes were compared between the two dose levels of Exendin-(9-39) of 300pmol/kg/min (3 subjects) and 500pmol/kg/min (3 subjects) were compared to the vehicle infusion (all 6 subjects).
Arm/Group Title Exendin-(9-39) 300pmol/kg/Min Dose Exendin-(9-39) 500pmol/kg/Min Dose Vehicle
Hide Arm/Group Description:
After 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.
After 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.
After 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.
Overall Number of Participants Analyzed 3 3 6
Mean (Standard Error)
Unit of Measure: mg*min/dl
22,192.5  (4,784.7) 25,207.1  (1,157.5) 21,715.9  (3,597.8)
2.Secondary Outcome
Title Mean Plasma Insulin Area Under the Curve (AUC 0-3h)
Hide 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.
Time Frame 3 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Changes were compared between the two dose levels of Exendin-(9-39) of 300pmol/kg/min (3 subjects) and 500pmol/kg/min (3 subjects) were compared to the vehicle infusion (all 6 subjects).
Arm/Group Title Exendin-(9-39) 300pmol/kg/Min Dose Exendin-(9-39) 500pmol/kg/Min Dose Vehicle
Hide Arm/Group Description:
After 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.
After 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.
After 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.
Overall Number of Participants Analyzed 3 3 6
Mean (Standard Error)
Unit of Measure: pmol*min/l
14,695.85  (12,662.9) 9,058.5  (7,562.7) 19,435.4  (10,392.6)
3.Secondary Outcome
Title Mean Acetaminophen Plasma Concentration Area Under the Curve (AUC 0-3h)
Hide 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.
Time Frame 3 hours
Hide Outcome Measure Data
Hide Analysis Population Description
AUC were compared between the two dose levels of Exendin-(9-39) of 300pmol/kg/min (3 subjects) and 500pmol/kg/min (3 subjects) were compared to the vehicle infusion (all 6 subjects).
Arm/Group Title Exendin-(9-39) 300pmol/kg/Min Dose Exendin-(9-39) 500pmol/kg/Min Dose Vehicle
Hide Arm/Group Description:
After 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.
After 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.
After 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.
Overall Number of Participants Analyzed 3 3 6
Mean (Standard Error)
Unit of Measure: μg*min/l
3,387.5  (898) 3,742.8  (124.3) 3,436.6  (465.2)
4.Secondary Outcome
Title Peak Plasma Glucagon-like Peptide-1 (GLP-1) Concentration During Infusion
Hide 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.
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
Hide Outcome Measure Data
Hide Analysis Population Description
Differences were compared between the two dose levels of Exendin-(9-39) of 300pmol/kg/min (3 subjects) and 500pmol/kg/min (3 subjects) were compared to the vehicle infusion (all 6 subjects).
Arm/Group Title Exendin-(9-39) 300pmol/kg/Min Dose Exendin-(9-39) 500pmol/kg/Min Dose Vehicle
Hide Arm/Group Description:
After 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.
After 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.
After 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.
Overall Number of Participants Analyzed 3 3 6
Mean (Standard Error)
Unit of Measure: pmol/l
65.8  (33.3) 75.2  (5.8) 72.8  (26.1)
5.Secondary Outcome
Title Peak Glucagon Concentration During Infusion
Hide 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.
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
Hide Outcome Measure Data
Hide Analysis Population Description
Differences in peak glucagon concentration were compared between the two dose levels of Exendin-(9-39) of 300pmol/kg/min (3 subjects) and 500pmol/kg/min (3 subjects) were compared to the vehicle infusion (all 6 subjects).
Arm/Group Title Exendin-(9-39) 300pmol/kg/Min Dose Exendin-(9-39) 500pmol/kg/Min Dose Vehicle
Hide Arm/Group Description:
After 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.
After 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.
After 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.
Overall Number of Participants Analyzed 3 3 6
Mean (Standard Error)
Unit of Measure: pg/ml
127.5  (75.7) 145.7  (33.6) 114.0  (50.1)
Time Frame 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Exendin-(9-39) 300pmol/kg/Min Dose Exendin-(9-39) 500pmol/kg/Min Dose Vehicle
Hide Arm/Group Description After 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. After 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. After 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.
All-Cause Mortality
Exendin-(9-39) 300pmol/kg/Min Dose Exendin-(9-39) 500pmol/kg/Min Dose Vehicle
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Exendin-(9-39) 300pmol/kg/Min Dose Exendin-(9-39) 500pmol/kg/Min Dose Vehicle
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/3 (0.00%)      0/6 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Exendin-(9-39) 300pmol/kg/Min Dose Exendin-(9-39) 500pmol/kg/Min Dose Vehicle
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/3 (0.00%)      2/6 (33.33%)    
Endocrine disorders       
Hypoglycemia   0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1
Gastrointestinal disorders       
Gastrostomy-tube discharge  [1]  0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1
Musculoskeletal and connective tissue disorders       
Muscle Spasm   0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1
Indicates events were collected by systematic assessment
[1]
Subject reported discharge from G-tube at home, after completion of study infusions
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.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Diva De Leon, MD
Organization: Children's Hospital of Philadelphia
Phone: 267-426-5529
EMail: DELEON@email.chop.edu
Layout table for additonal information
Responsible Party: Diva De Leon, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01162499     History of Changes
Other Study ID Numbers: 09-007372
First Submitted: May 4, 2010
First Posted: July 14, 2010
Results First Submitted: July 29, 2016
Results First Posted: November 9, 2016
Last Update Posted: October 23, 2017