Trial Outcomes & Findings for Regulation of Insulin Secretion by the GLP-1 Receptor (NCT NCT02844907)
NCT ID: NCT02844907
Last Updated: 2024-12-12
Results Overview
Primary variable for analysis will be C-peptide during the clamp. Mean values will be compared between the control and dexamethasone studies for C-peptide levels during the hyperglycemia plus exendin-(9-39) period of the clamps. For each subject the mean C-peptide during the 60-90 minute period of the initial study (with no dexamethasone) will be compared to the 60-120 period with dexamethasone.
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
6 participants
Primary outcome timeframe
Minute infusion periods (0-60 vs 60-120) baseline and treatment (Dex vs no Dex)
Results posted on
2024-12-12
Participant Flow
Aim 3 not initiated, no participants enrolled in Aim 3 Arms/Groups
Participant milestones
| Measure |
Hyperglycemic Clamp + Exendin (9-39)
During the 2-hour procedure, a variable infusion of 20% dextrose and blood glucose will be clamped at basal + 3mM. Participants will receive an infusion of the GLP-1 receptor antagonist Exendin (9-39) between the 60-120 minute time-points of the clamp. The amount of Ex-9 infused will be 750 pmol/kg/min for 60 minutes.
Exendin (9-39): Upon establishing a hyperglycemic clamp (target blood glucose at basal +3 mM) Exendin (9-39) will be infused.
Hyperglycemic Clamp: A variable infusion of 20% dextrose will begin to clamp the blood glucose at basal +3 mM.
|
|---|---|
|
Hyperglycemic Clamp + Exendin (9-39)
STARTED
|
6
|
|
Hyperglycemic Clamp + Exendin (9-39)
COMPLETED
|
6
|
|
Hyperglycemic Clamp + Exendin (9-39)
NOT COMPLETED
|
0
|
|
With Dexamethasone
STARTED
|
6
|
|
With Dexamethasone
COMPLETED
|
5
|
|
With Dexamethasone
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Hyperglycemic Clamp + Exendin (9-39)
During the 2-hour procedure, a variable infusion of 20% dextrose and blood glucose will be clamped at basal + 3mM. Participants will receive an infusion of the GLP-1 receptor antagonist Exendin (9-39) between the 60-120 minute time-points of the clamp. The amount of Ex-9 infused will be 750 pmol/kg/min for 60 minutes.
Exendin (9-39): Upon establishing a hyperglycemic clamp (target blood glucose at basal +3 mM) Exendin (9-39) will be infused.
Hyperglycemic Clamp: A variable infusion of 20% dextrose will begin to clamp the blood glucose at basal +3 mM.
|
|---|---|
|
With Dexamethasone
No IV access
|
1
|
Baseline Characteristics
Regulation of Insulin Secretion by the GLP-1 Receptor
Baseline characteristics by cohort
| Measure |
Hyperglycemic Clamp + Exendin (9-39)
n=6 Participants
During the 2-hour procedure, a variable infusion of 20% dextrose and blood glucose will be clamped at basal + 3mM. Participants will receive an infusion of the GLP-1 receptor antagonist Exendin (9-39) between the 60-120 minute time-points of the clamp. The amount of Ex-9 infused will be 750 pmol/kg/min for 60 minutes.
Exendin (9-39): Upon establishing a hyperglycemic clamp (target blood glucose at basal +3 mM) Exendin (9-39) will be infused.
Hyperglycemic Clamp: A variable infusion of 20% dextrose will begin to clamp the blood glucose at basal +3 mM.
Each subject then received dexamethasone 4 mg daily for 7 days and returned for an identical experiment with a hyperglycemic clamp and exendin-(9-39).
|
|---|---|
|
Age, Continuous
|
34 years
STANDARD_DEVIATION 4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 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
|
5 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
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Minute infusion periods (0-60 vs 60-120) baseline and treatment (Dex vs no Dex)Population: Data not collected for one subject
Primary variable for analysis will be C-peptide during the clamp. Mean values will be compared between the control and dexamethasone studies for C-peptide levels during the hyperglycemia plus exendin-(9-39) period of the clamps. For each subject the mean C-peptide during the 60-90 minute period of the initial study (with no dexamethasone) will be compared to the 60-120 period with dexamethasone.
Outcome measures
| Measure |
Hyperglycemic Clamp + Exendin (9-39)
n=5 Participants
During the 2-hour procedure, a variable infusion of 20% dextrose and blood glucose will be clamped at basal + 3mM. Participants will receive an infusion of the GLP-1 receptor antagonist Exendin (9-39) between the 60-120 minute time-points of the clamp. The amount of Ex-9 infused will be 750 pmol/kg/min for 60 minutes.
Exendin (9-39): Upon establishing a hyperglycemic clamp (target blood glucose at basal +3 mM) Exendin (9-39) will be infused.
Hyperglycemic Clamp: A variable infusion of 20% dextrose will begin to clamp the blood glucose at basal +3 mM.
Each subject then received dexamethasone 4 mg daily for 7 days and returned for an identical experiment with a hyperglycemic clamp and exendin-(9-39).
|
|---|---|
|
AIM2: C-peptide Levels.
Control + exendin-(9-39)
|
10,335 ng/ml
Standard Error 1984
|
|
AIM2: C-peptide Levels.
Dexamethasone + exendin-(9-39)
|
9042 ng/ml
Standard Error 1255
|
PRIMARY outcome
Timeframe: Minute infusion periods (0-60 vs 60-120)Population: Data not collected
The fasting GLP-1 effect will be defined as the difference in steady state glucose stimulated insulin secretion with and without Ex-9.
Outcome measures
Outcome data not reported
Adverse Events
Hyperglycemic Clamp + Exendin (9-39) With Dexamethasone
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Hyperglycemic Clamp + Exendin (9-39) Without Dexamethasone
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Hyperglycemic Clamp + Exendin (9-39) With Dexamethasone
n=6 participants at risk
During the 2-hour procedure, a variable infusion of 20% dextrose and blood glucose will be clamped at basal + 3mM. Participants will receive an infusion of the GLP-1 receptor antagonist Exendin (9-39) between the 60-120 minute time-points of the clamp. The amount of Ex-9 infused will be 750 pmol/kg/min for 60 minutes.
Exendin (9-39): Upon establishing a hyperglycemic clamp (target blood glucose at basal +3 mM) Exendin (9-39) will be infused.
Hyperglycemic Clamp: A variable infusion of 20% dextrose will begin to clamp the blood glucose at basal +3 mM.
Each subject then received dexamethasone 4 mg daily for 7 days and returned for an identical experiment with a hyperglycemic clamp and exendin-(9-39).
The study protocol and exposures were identical for each subject on the 1 (six subjects) or 2 (five subjects) days they were studied, and differed only by preceding dexamethasone treatment (5 subjects). Other Adverse Events are reported above separately for the experiments with and without dexamethasone.
|
Hyperglycemic Clamp + Exendin (9-39) Without Dexamethasone
n=6 participants at risk
During the 2-hour procedure, a variable infusion of 20% dextrose and blood glucose will be clamped at basal + 3mM. Participants will receive an infusion of the GLP-1 receptor antagonist Exendin (9-39) between the 60-120 minute time-points of the clamp. The amount of Ex-9 infused will be 750 pmol/kg/min for 60 minutes.
Exendin (9-39): Upon establishing a hyperglycemic clamp (target blood glucose at basal +3 mM) Exendin (9-39) will be infused.
Hyperglycemic Clamp: A variable infusion of 20% dextrose will begin to clamp the blood glucose at basal +3 mM.
Each subject then received dexamethasone 4 mg daily for 7 days and returned for an identical experiment with a hyperglycemic clamp and exendin-(9-39).
The study protocol and exposures were identical for each subject on the 1 (six subjects) or 2 (five subjects) days they were studied, and differed only by preceding dexamethasone treatment (5 subjects). Other Adverse Events are reported above separately for the experiments with and without dexamethasone.
|
|---|---|---|
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General disorders
Bruising at IV site
|
50.0%
3/6 • Number of events 3 • 2 weeks
|
0.00%
0/6 • 2 weeks
|
|
General disorders
Transient Nausea
|
16.7%
1/6 • Number of events 1 • 2 weeks
|
16.7%
1/6 • Number of events 1 • 2 weeks
|
|
General disorders
Dizziness
|
0.00%
0/6 • 2 weeks
|
33.3%
2/6 • Number of events 2 • 2 weeks
|
|
General disorders
Blood glucose levels between 70 and 80 mg/dl that were asymptomatic
|
0.00%
0/6 • 2 weeks
|
33.3%
2/6 • Number of events 2 • 2 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place