Trial Outcomes & Findings for Effect of Exendin-(9-39) on Glycemic Control in Subjects With Congenital Hyperinsulinism (NCT NCT00571324)

NCT ID: NCT00571324

Last Updated: 2017-12-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

9 participants

Primary outcome timeframe

6 hours

Results posted on

2017-12-11

Participant Flow

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

Participant milestones

Participant milestones
Measure
Exendin-(9-39) First, the Vehicle
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.
Vehicle First, Then Exendin-(9-39)
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.
Intervention 1 (7 Hours)
STARTED
5
4
Intervention 1 (7 Hours)
COMPLETED
5
4
Intervention 1 (7 Hours)
NOT COMPLETED
0
0
Intervention 2 (7 Hours)
STARTED
5
4
Intervention 2 (7 Hours)
COMPLETED
5
4
Intervention 2 (7 Hours)
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Subject Population
n=9 Participants
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
4 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
5 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
3 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
0 Participants
n=5 Participants
Race (NIH/OMB)
White
9 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
9 participants
n=5 Participants
Mutation (ABCC8)
Heterozygous dominant ABCC8 mutations
6 participants
n=5 Participants
Mutation (ABCC8)
Homozygous common recessive Ashkenazi mutation
2 participants
n=5 Participants
Mutation (ABCC8)
Compound heterozygous recessive ABCC8 mutations
1 participants
n=5 Participants
Pancreatectomy
None
6 participants
n=5 Participants
Pancreatectomy
85% Pancreatectomy
1 participants
n=5 Participants
Pancreatectomy
95% Pancreatectomy
2 participants
n=5 Participants

PRIMARY outcome

Timeframe: 6 hours

Population: Subjects served as their own control for comparison between effects of Exendin-(9-39) and the normal saline vehicle.

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.

Outcome measures

Outcome measures
Measure
Exendin-(9-39)
n=9 Participants
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.
Vehicle
n=9 Participants
Normal saline vehicle infusion was administered intravenously (IV) after an overnight fast. The infusion was given over 6 hours.
Mean Blood Glucose Area Under the Curve (AUC 0-6h)
2,096 mmol*min/L
Standard Error 454
1,678 mmol*min/L
Standard Error 281

SECONDARY outcome

Timeframe: 6 hours

Population: Subjects served as their own control for comparison between effects of Exendin-(9-39) and the normal saline vehicle.

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.

Outcome measures

Outcome measures
Measure
Exendin-(9-39)
n=9 Participants
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.
Vehicle
n=9 Participants
Normal saline vehicle infusion was administered intravenously (IV) after an overnight fast. The infusion was given over 6 hours.
Mean Plasma Insulin Area Under the Curve (AUC 0-6h)
21,016 pmol*min/L
Standard Error 7,410
25,842 pmol*min/L
Standard Error 12,397

SECONDARY outcome

Timeframe: 6 hours

Population: Subjects served as their own control for comparison between effects of Exendin-(9-39) and the normal saline vehicle.

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.

Outcome measures

Outcome measures
Measure
Exendin-(9-39)
n=9 Participants
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.
Vehicle
n=9 Participants
Normal saline vehicle infusion was administered intravenously (IV) after an overnight fast. The infusion was given over 6 hours.
Mean Plasma Glucagon Area Under the Curve (AUC 0-6h)
21,243 pg*min/dL
Standard Error 5,836
21,867 pg*min/dL
Standard Error 4,432

SECONDARY outcome

Timeframe: 6 hours

Population: Subjects served as their own control for comparison between effects of Exendin-(9-39) and the normal saline vehicle.

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.

Outcome measures

Outcome measures
Measure
Exendin-(9-39)
n=9 Participants
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.
Vehicle
n=9 Participants
Normal saline vehicle infusion was administered intravenously (IV) after an overnight fast. The infusion was given over 6 hours.
Mean Plasma Intact Glucagon-Like Peptide-1 (GLP-1) Area Under the Curve (AUC 0-6h)
1,970 pmol*min/L
Standard Error 1,284
1,992 pmol*min/L
Standard Error 1,203

Adverse Events

Exendin-(9-39)

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Vehicle

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Exendin-(9-39)
n=9 participants at risk
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.
Vehicle
n=9 participants at risk
Normal saline vehicle infusion was administered intravenously (IV) after an overnight fast. The infusion was given over 6 hours.
Endocrine disorders
Hypoglycemia
0.00%
0/9 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)
33.3%
3/9 • Number of events 3 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)
General disorders
Headache
0.00%
0/9 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)
11.1%
1/9 • Number of events 1 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)

Additional Information

Diva De Leon, MD

Children's Hospital of Philadelphia

Phone: 267-426-5529

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place