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Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity

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ClinicalTrials.gov Identifier: NCT00897676
Recruitment Status : Completed
First Posted : May 12, 2009
Results First Posted : January 18, 2018
Last Update Posted : June 21, 2019
Sponsor:
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: Treatment
Condition Congenital Hyperinsulinism
Interventions Drug: Exendin-(9-39)
Drug: placebo
Enrollment 17
Recruitment Details Subjects age 6months to 18 years with congenital hyperinsulinism due to mutations in the Katp channel( KatpHI) were recruited from the Hyperinsulinism Center at The Children's Hospital of Philadelphia
Pre-assignment Details 17 subject were enrolled (consented). One(1) withdrawn
Arm/Group Title Vehicle First Then Exendin-(9-39) Exendin-(9-39) First Then Vehicle
Hide Arm/Group Description

An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). At time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. The following day, at time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, glucagon-like peptide-(GLP-1) , and glucagon will be measured every 30 minutes.

Vehicle: (0.9% NaCl)

An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). At time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. The following day, at time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, glucagon-like peptide-(GLP-1) , and glucagon will be measured every 30 minutes.

Exendin-(9-39): 100-500pmol/kg/min

Period Title: Intervention 1(6 Hours)
Started 9 7
Completed 9 7
Not Completed 0 0
Period Title: Intervention 2(6 Hours)
Started 9 7
Completed 9 7
Not Completed 0 0
Arm/Group Title Subject Population
Hide Arm/Group Description 9 subjects were randomized to the vehicle first arm and the next day they were switched to exendin- (9-39). 7 subjects were randomized to the exendin-(9-39) first arm and the next day they were switched to vehicle. 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 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
<=18 years
16
 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 16 participants
Female
6
  37.5%
Male
10
  62.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 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
1
   6.3%
White
15
  93.8%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 16 participants
16
 100.0%
1.Primary Outcome
Title Area Under the Curve (AUC) Plasma Glucose
Hide Description Area under the curve plasma glucose from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
Time Frame Time 0 min - time 360 min
Hide Outcome Measure Data
Hide Analysis Population Description
A total of 16 subjects were included in the analysis. 1 subject was withdrawn.
Arm/Group Title Vehicle Exendin-(9-39)
Hide Arm/Group Description:

Subjects received an infusion of vehicle( 0.9%NaCl) intravenously from time 0 min to 360 min

Vehicle: (0.9% NaCl)

Subjects received an infusion of exendin-(9-39) intravenously at a dose ranging from 100-500pmol/kg/min from time 0 min to 360 min

Exendin-(9-39)

Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: mg*min/dL
26994.7  (4219.8) 32122.2  (6650.1)
2.Secondary Outcome
Title Area Under the Curve (AUC) Plasma Insulin
Hide Description Area under the curve plasma insulin from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
Time Frame time 0 min to time 360 min
Hide Outcome Measure Data
Hide Analysis Population Description
data from only 15 subjects because the values were below the level of detection for one subject.
Arm/Group Title Vehicle Exendin-(9-39)
Hide Arm/Group Description:

Subjects received an infusion of vehicle( 0.9%NaCl) intravenously from time 0 to time 360 min

Vehicle: (0.9% NaCl)

Subjects received an infusion of exendin-(9-39) intravenously from time 0 to time 360 min at a dose of 100-500 pmol/kg/min

Exendin-(9-39)

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: uIU*min/mL
1578.7  (1089.9) 1284.5  (553.7)
3.Secondary Outcome
Title Area Under the Curve (AUC) Plasma C-peptide
Hide Description Area under the curve plasma C-peptide from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Time Frame time 0 min to time 360 min
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vehicle Exendin-(9-39)
Hide Arm/Group Description:

Subjects received an infusion of vehicle( 0.9%NaCl) intravenously from time 0 min to time 360 min

Vehicle: (0.9% NaCl)

Subjects received an infusion of exendin-(9-39) intravenously at a dose ranging from 100-500pmol/kg/min from time 0 min to time 360 min

Exendin-(9-39)

Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: ng*min/mL
281.4  (155.8) 236.6  (112.5)
4.Secondary Outcome
Title Area Under the Curve (AUC) Plasma Glucagon
Hide Description Area under the curve plasma glucagon from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Time Frame time 0 min to time 360 min
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vehicle Exendin-(9-39)
Hide Arm/Group Description:

Subjects receive an infusion of vehicle( 0.9%NaCl) intravenously from time 0 to time 360 min

Vehicle: (0.9% NaCl)

Subjects received an infusion of exendin-(9-39) intravenously at a dose ranging from 100-500pmol/kg/min from time 0 to time 360 min

Exendin-(9-39)

Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: pg*min/mL
22806.8  (10210.3) 23409.4  (11396.1)
5.Secondary Outcome
Title Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1)
Hide Description Area under the curve plasma total GLP-1 (glucagon-like peptide-1) from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Time Frame time 0 to time 360 min
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vehicle Exendin-(9-39)
Hide Arm/Group Description:

Subjects received an infusion of vehicle( 0.9%NaCl) intravenously from time 0 to time 360 min

Vehicle: (0.9% NaCl)

Subjects received an infusion of exendin-(9-39) intravenously at a dose ranging from 100-500pmol/kg/min from time 0 to time 360 min

Exendin-(9-39)

Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: pmol*min/L
4899.3  (2598.8) 5698.8  (3484.8)
6.Secondary Outcome
Title Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1)
Hide Description Area under the curve plasma active GLP-1 (glucagon-like peptide-1) from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Time Frame time 0 min to time 360 min
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vehicle Exendin-(9-39)
Hide Arm/Group Description:

Subjects received an infusion of vehicle( 0.9%NaCl) intravenously from time 0 min to time 360 min

Vehicle

Subjects received an infusion of exendin-(9-39) intravenously at a dose ranging from 100-500pmol/kg/min from time 0 min to time 360 min

Exendin-(9-39)

Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: pmol*min/L
1373.7  (1044) 1432.9  (1114.3)
Time Frame baseline to 24 hours after the end of study of infusion.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vehicle Exendin-(9-39)
Hide Arm/Group Description

Subjects received an infusion of vehicle (0.9% NaCl) intravenously from time 0 min to time 360 min

Vehicle: (0.9% NaCl)

Subjects received an infusion of exendin-(9-39) intravenously at a dose ranging from 100-500pmol/kg/min from time 0 min to time 360 min

Exendin-(9-39)

All-Cause Mortality
Vehicle Exendin-(9-39)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)      0/16 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Vehicle Exendin-(9-39)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/16 (0.00%)      0/16 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Vehicle Exendin-(9-39)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/16 (75.00%)      8/16 (50.00%)    
Endocrine disorders     
hypoglycemia   11/16 (68.75%)  11 7/16 (43.75%)  7
hyperglycemia   1/16 (6.25%)  1 0/16 (0.00%)  0
Gastrointestinal disorders     
Emesis   0/16 (0.00%)  0 1/16 (6.25%)  1
Indicates events were collected by systematic assessment
For safety reasons, blood glucose levels were maintained above a safety threshold (55-60mg/dL) during the study by infusing dextrose intravenously which may limit the magnitude of the effect that we will be able to detect.
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 DeLeon, MD
Organization: The 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: NCT00897676     History of Changes
Other Study ID Numbers: 2008-10-6255
R01FD004905 ( Other Grant/Funding Number: US Food and Drug Administration )
First Submitted: May 8, 2009
First Posted: May 12, 2009
Results First Submitted: November 9, 2017
Results First Posted: January 18, 2018
Last Update Posted: June 21, 2019