Trial Outcomes & Findings for Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity (NCT NCT00897676)
NCT ID: NCT00897676
Last Updated: 2020-03-13
Results Overview
Area under the curve plasma glucose from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
17 participants
Primary outcome timeframe
Time 0 min - time 360 min
Results posted on
2020-03-13
Participant Flow
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
17 subject were enrolled (consented). One(1) withdrawn
Participant milestones
| Measure |
Vehicle First Then Exendin-(9-39)
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)
|
Exendin-(9-39) First Then Vehicle
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
|
|---|---|---|
|
Intervention 1(6 Hours)
STARTED
|
9
|
7
|
|
Intervention 1(6 Hours)
COMPLETED
|
9
|
7
|
|
Intervention 1(6 Hours)
NOT COMPLETED
|
0
|
0
|
|
Intervention 2(6 Hours)
STARTED
|
9
|
7
|
|
Intervention 2(6 Hours)
COMPLETED
|
9
|
7
|
|
Intervention 2(6 Hours)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity
Baseline characteristics by cohort
| Measure |
Subject Population
n=16 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
16 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Time 0 min - time 360 minPopulation: A total of 16 subjects were included in the analysis. 1 subject was withdrawn.
Area under the curve plasma glucose from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
Outcome measures
| Measure |
Vehicle
n=16 Participants
Subjects received an infusion of vehicle( 0.9%NaCl) intravenously from time 0 min to 360 min
Vehicle: (0.9% NaCl)
|
Exendin-(9-39)
n=16 Participants
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)
|
|---|---|---|
|
Area Under the Curve (AUC) Plasma Glucose
|
26994.7 mg*min/dL
Standard Deviation 4219.8
|
32122.2 mg*min/dL
Standard Deviation 6650.1
|
SECONDARY outcome
Timeframe: time 0 min to time 360 minPopulation: data from only 15 subjects because the values were below the level of detection for one subject.
Area under the curve plasma insulin from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
Outcome measures
| Measure |
Vehicle
n=15 Participants
Subjects received an infusion of vehicle( 0.9%NaCl) intravenously from time 0 min to 360 min
Vehicle: (0.9% NaCl)
|
Exendin-(9-39)
n=15 Participants
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)
|
|---|---|---|
|
Area Under the Curve (AUC) Plasma Insulin
|
1578.7 uIU*min/mL
Standard Deviation 1089.9
|
1284.5 uIU*min/mL
Standard Deviation 553.7
|
SECONDARY outcome
Timeframe: time 0 min to time 360 minArea under the curve plasma C-peptide from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Outcome measures
| Measure |
Vehicle
n=16 Participants
Subjects received an infusion of vehicle( 0.9%NaCl) intravenously from time 0 min to 360 min
Vehicle: (0.9% NaCl)
|
Exendin-(9-39)
n=16 Participants
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)
|
|---|---|---|
|
Area Under the Curve (AUC) Plasma C-peptide
|
281.4 ng*min/mL
Standard Deviation 155.8
|
236.6 ng*min/mL
Standard Deviation 112.5
|
SECONDARY outcome
Timeframe: time 0 min to time 360 minArea under the curve plasma glucagon from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Outcome measures
| Measure |
Vehicle
n=16 Participants
Subjects received an infusion of vehicle( 0.9%NaCl) intravenously from time 0 min to 360 min
Vehicle: (0.9% NaCl)
|
Exendin-(9-39)
n=16 Participants
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)
|
|---|---|---|
|
Area Under the Curve (AUC) Plasma Glucagon
|
22806.8 pg*min/mL
Standard Deviation 10210.3
|
23409.4 pg*min/mL
Standard Deviation 11396.1
|
SECONDARY outcome
Timeframe: time 0 to time 360 minArea 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
Outcome measures
| Measure |
Vehicle
n=16 Participants
Subjects received an infusion of vehicle( 0.9%NaCl) intravenously from time 0 min to 360 min
Vehicle: (0.9% NaCl)
|
Exendin-(9-39)
n=16 Participants
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)
|
|---|---|---|
|
Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1)
|
4899.3 pmol*min/L
Standard Deviation 2598.8
|
5698.8 pmol*min/L
Standard Deviation 3484.8
|
SECONDARY outcome
Timeframe: time 0 min to time 360 minArea 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
Outcome measures
| Measure |
Vehicle
n=16 Participants
Subjects received an infusion of vehicle( 0.9%NaCl) intravenously from time 0 min to 360 min
Vehicle: (0.9% NaCl)
|
Exendin-(9-39)
n=16 Participants
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)
|
|---|---|---|
|
Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1)
|
1373.7 pmol*min/L
Standard Deviation 1044
|
1432.9 pmol*min/L
Standard Deviation 1114.3
|
Adverse Events
Vehicle
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Exendin-(9-39)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Vehicle
n=16 participants at risk
Subjects received an infusion of vehicle (0.9% NaCl) intravenously from time 0 min to time 360 min
Vehicle: (0.9% NaCl)
|
Exendin-(9-39)
n=16 participants at risk
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)
|
|---|---|---|
|
Endocrine disorders
hypoglycemia
|
68.8%
11/16 • Number of events 11 • baseline to 24 hours after the end of study of infusion.
|
43.8%
7/16 • Number of events 7 • baseline to 24 hours after the end of study of infusion.
|
|
Endocrine disorders
hyperglycemia
|
6.2%
1/16 • Number of events 1 • baseline to 24 hours after the end of study of infusion.
|
0.00%
0/16 • baseline to 24 hours after the end of study of infusion.
|
|
Gastrointestinal disorders
Emesis
|
0.00%
0/16 • baseline to 24 hours after the end of study of infusion.
|
6.2%
1/16 • Number of events 1 • baseline to 24 hours after the end of study of infusion.
|
Additional Information
Diva DeLeon, MD
The Children's Hospital of Philadelphia
Phone: 267-426-5529
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place