Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 28 of 7576 for:    Area Under Curve

Effect of Exendin-(9-39) on Glycemic Control in Subjects With Congenital Hyperinsulinism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00571324
Recruitment Status : Completed
First Posted : December 12, 2007
Results First Posted : November 9, 2016
Last Update Posted : December 11, 2017
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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 Congenital Hyperinsulinism
Interventions Drug: Exendin-(9-39)
Other: Vehicle
Enrollment 9
Recruitment Details Subjects with confirmed genetic and clinical diagnosis of Adenosine triphosphate (ATP)-sensitive potassium channels (KATP) hyperinsulinism were recruited from the Hyperinsulinism Center at the Children's Hospital of Philadelphia
Pre-assignment Details  
Arm/Group Title Exendin-(9-39) First, the Vehicle Vehicle First, Then Exendin-(9-39)
Hide Arm/Group Description Exendin-(9-39) was administered intravenously (IV) after an overnight fast. Exendin-(9-39) was infused over 6 hours with the dose slowly escalating from 100pmol/kg/min for 2 hours, then 300pmol/kg/min for another 2 hours followed by 500pmol/kg/min for the last 2 hours of the infusion. The following day, after another overnight fast, normal saline (control) vehicle infusion was administered intravenously (IV) over 6 hours. During both infusions, blood glucose levels were measured every 20 minutes. Normal saline vehicle infusion was administered intravenously (IV) after an overnight fast. The infusion was given over 6 hours. The following day, after another overnight fast, Exendin-(9-39) was infused over 6 hours with the dose slowly escalating from 100pmol/kg/min for 2 hours, then 300pmol/kg/min for another 2 hours followed by 500pmol/kg/min for the last 2 hours of the infusion. During both infusions, blood glucose levels were measured every 20 minutes.
Period Title: Intervention 1 (7 Hours)
Started 5 4
Completed 5 4
Not Completed 0 0
Period Title: Intervention 2 (7 Hours)
Started 5 4
Completed 5 4
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 9
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
<=18 years
4
  44.4%
Between 18 and 65 years
5
  55.6%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Female
6
  66.7%
Male
3
  33.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 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
9
 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 9 participants
9
Mutation (ABCC8)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants
Heterozygous dominant ABCC8 mutations 6
Homozygous common recessive Ashkenazi mutation 2
Compound heterozygous recessive ABCC8 mutations 1
Pancreatectomy   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants
None 6
85% Pancreatectomy 1
95% Pancreatectomy 2
[1]
Measure Description: Whether subject has undergone prior pancreatectomy during infancy and if so, what percent of the pancreas was removed.
1.Primary Outcome
Title Mean Blood Glucose Area Under the Curve (AUC 0-6h)
Hide Description To examine the effect of Exendin-(9-39) on fasting blood 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 20 minutes until 6 hours after the start of the infusion. Using this information, the mean blood glucose area under the curve (AUC) from the start of the infusion to the end of the infusion (360 minutes) was calculated for each both Exendin-(9-39) and vehicle and compared.
Time Frame 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects served as their own control for comparison between effects of Exendin-(9-39) and the normal saline vehicle.
Arm/Group Title Exendin-(9-39) Vehicle
Hide Arm/Group Description:
Exendin-(9-39) was administered intravenously (IV) after an overnight fast. Exendin-(9-39) was infused over 6 hours with the dose slowly escalating from 100pmol/kg/min for 2 hours, then 300pmol/kg/min for another 2 hours followed by 500pmol/kg/min for the last 2 hours of the infusion.
Normal saline vehicle infusion was administered intravenously (IV) after an overnight fast. The infusion was given over 6 hours.
Overall Number of Participants Analyzed 9 9
Mean (Standard Error)
Unit of Measure: mmol*min/L
2,096  (454) 1,678  (281)
2.Secondary Outcome
Title Mean Plasma Insulin Area Under the Curve (AUC 0-6h)
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 20 minutes until 6 hours after the start of the infusion. Using this information, the mean plasma insulin area under the curve (AUC) from the start of the infusion to the end of the infusion (360 minutes) was calculated for each both Exendin-(9-39) and vehicle and compared.
Time Frame 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects served as their own control for comparison between effects of Exendin-(9-39) and the normal saline vehicle.
Arm/Group Title Exendin-(9-39) Vehicle
Hide Arm/Group Description:
Exendin-(9-39) was administered intravenously (IV) after an overnight fast. Exendin-(9-39) was infused over 6 hours with the dose slowly escalating from 100pmol/kg/min for 2 hours, then 300pmol/kg/min for another 2 hours followed by 500pmol/kg/min for the last 2 hours of the infusion.
Normal saline vehicle infusion was administered intravenously (IV) after an overnight fast. The infusion was given over 6 hours.
Overall Number of Participants Analyzed 9 9
Mean (Standard Error)
Unit of Measure: pmol*min/L
21,016  (7,410) 25,842  (12,397)
3.Secondary Outcome
Title Mean Plasma Glucagon Area Under the Curve (AUC 0-6h)
Hide Description To examine the effect of Exendin-(9-39) on plasma glucagon 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 20 minutes until 6 hours after the start of the infusion. Using this information, the mean plasma glucagon area under the curve (AUC) from the start of the infusion to the end of the infusion (360 minutes) was calculated for each both Exendin-(9-39) and vehicle and compared.
Time Frame 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects served as their own control for comparison between effects of Exendin-(9-39) and the normal saline vehicle.
Arm/Group Title Exendin-(9-39) Vehicle
Hide Arm/Group Description:
Exendin-(9-39) was administered intravenously (IV) after an overnight fast. Exendin-(9-39) was infused over 6 hours with the dose slowly escalating from 100pmol/kg/min for 2 hours, then 300pmol/kg/min for another 2 hours followed by 500pmol/kg/min for the last 2 hours of the infusion.
Normal saline vehicle infusion was administered intravenously (IV) after an overnight fast. The infusion was given over 6 hours.
Overall Number of Participants Analyzed 9 9
Mean (Standard Error)
Unit of Measure: pg*min/dL
21,243  (5,836) 21,867  (4,432)
4.Secondary Outcome
Title Mean Plasma Intact Glucagon-Like Peptide-1 (GLP-1) Area Under the Curve (AUC 0-6h)
Hide Description To examine the effect of Exendin-(9-39) on plasma intact glucagon-like Peptide-1 (GLP-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 20 minutes until 6 hours after the start of the infusion. Using this information, the mean intact GLP-1 area under the curve (AUC) from the start of the infusion to the end of the infusion (360 minutes) was calculated for each both Exendin-(9-39) and vehicle and compared.
Time Frame 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects served as their own control for comparison between effects of Exendin-(9-39) and the normal saline vehicle.
Arm/Group Title Exendin-(9-39) Vehicle
Hide Arm/Group Description:
Exendin-(9-39) was administered intravenously (IV) after an overnight fast. Exendin-(9-39) was infused over 6 hours with the dose slowly escalating from 100pmol/kg/min for 2 hours, then 300pmol/kg/min for another 2 hours followed by 500pmol/kg/min for the last 2 hours of the infusion.
Normal saline vehicle infusion was administered intravenously (IV) after an overnight fast. The infusion was given over 6 hours.
Overall Number of Participants Analyzed 9 9
Mean (Standard Error)
Unit of Measure: pmol*min/L
1,970  (1,284) 1,992  (1,203)
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) Vehicle
Hide Arm/Group Description Exendin-(9-39) was administered intravenously (IV) after an overnight fast. Exendin-(9-39) was infused over 6 hours with the dose slowly escalating from 100pmol/kg/min for 2 hours, then 300pmol/kg/min for another 2 hours followed by 500pmol/kg/min for the last 2 hours of the infusion. Normal saline vehicle infusion was administered intravenously (IV) after an overnight fast. The infusion was given over 6 hours.
All-Cause Mortality
Exendin-(9-39) Vehicle
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Exendin-(9-39) Vehicle
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/9 (0.00%)      0/9 (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) Vehicle
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/9 (0.00%)      4/9 (44.44%)    
Endocrine disorders     
Hypoglycemia   0/9 (0.00%)  0 3/9 (33.33%)  3
General disorders     
Headache   0/9 (0.00%)  0 1/9 (11.11%)  1
Indicates events were collected by systematic assessment
Due to safety concerns subjects with symptomatic hypoglycemia were rescued with dextrose to maintain glucose levels >60mg/dL limiting detectable treatment effect.
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: NCT00571324     History of Changes
Other Study ID Numbers: 2007-1-5131
R03DK078535-01 ( U.S. NIH Grant/Contract )
First Submitted: December 10, 2007
First Posted: December 12, 2007
Results First Submitted: July 29, 2016
Results First Posted: November 9, 2016
Last Update Posted: December 11, 2017