Trial Outcomes & Findings for A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion (NCT NCT04459338)

Results Overview

This is the area under the curve for insulin secretion over the duration of the hyperglycemic clamp (0 to 300 minutes during the study in the Clinical Research Unit).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

11 participants

Primary outcome timeframe

Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study

Results posted on

2023-06-09

Participant Flow

Healthy volunteers responded to intramural advertising at the Mayo Clinic between March 2021 and September 2021

None of the enrolled subjects were excluded and all were randomized

Participant milestones

Participant milestones
Measure	Saline, Then Exendin-9,39 Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Saline infusion is started at time 0 and continues for 300 minutes. There is then a washout period of 14 days minimum Subjects are admitted to the Clinical research unit the night before the 2nd study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Exendin-9,39 infusion is started at time 0 and continues for 300 minutes.	Exendin-9,39, Then Saline Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Exendin-9,39 infusion is started at time 0 and continues for 300 minutes. There is then a washout period of 14 days minimum Subjects are admitted to the Clinical research unit the night before the 2nd study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Saline infusion is started at time 0 and continues for 300 minutes.
Overall Study STARTED	5	6
Overall Study COMPLETED	4	6
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Saline, Then Exendin-9,39 Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Saline infusion is started at time 0 and continues for 300 minutes. There is then a washout period of 14 days minimum Subjects are admitted to the Clinical research unit the night before the 2nd study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Exendin-9,39 infusion is started at time 0 and continues for 300 minutes.	Exendin-9,39, Then Saline Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Exendin-9,39 infusion is started at time 0 and continues for 300 minutes. There is then a washout period of 14 days minimum Subjects are admitted to the Clinical research unit the night before the 2nd study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Saline infusion is started at time 0 and continues for 300 minutes.
Overall Study Loss of IV during study	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=11 Participants All participants were randomized to receive all interventions
Age, Categorical <=18 years	0 Participants n=11 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=11 Participants
Age, Categorical >=65 years	0 Participants n=11 Participants
Age, Continuous	26 years STANDARD_DEVIATION 3 • n=11 Participants
Sex: Female, Male Female	9 Participants n=11 Participants
Sex: Female, Male Male	2 Participants n=11 Participants
Region of Enrollment United States	11 participants n=11 Participants

PRIMARY outcome

Timeframe: Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study

This is the area under the curve for insulin secretion over the duration of the hyperglycemic clamp (0 to 300 minutes during the study in the Clinical Research Unit).

Outcome measures

Outcome measures
Measure	Insulin Secretion During the Saline Study n=11 Participants Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Saline infusion is started at time 0 and continues for 300 minutes.	Insulin Secretion During the Exendin-9,39 Study n=10 Participants Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Exendin-9,39 infusion is started at time 0 and continues for 300 minutes.
Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion	191 nmol/min per 300 min Standard Error 23	171 nmol/min per 300 min Standard Error 19

Adverse Events

Saline

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Exendin-9,39

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Saline n=11 participants at risk Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Saline infusion is started at time 0 and continues for 300 minutes.	Exendin-9,39 n=11 participants at risk Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Exendin-9,39 infusion is started at time 0 and continues for 300 minutes.
Skin and subcutaneous tissue disorders Infusion line lost	9.1% 1/11 • Number of events 1 • Time between screening and completion of the study = 6 weeks	0.00% 0/11 • Time between screening and completion of the study = 6 weeks
Gastrointestinal disorders Nausea	9.1% 1/11 • Number of events 1 • Time between screening and completion of the study = 6 weeks	0.00% 0/11 • Time between screening and completion of the study = 6 weeks

Additional Information

Adrian Vella

Mayo Clinic

Phone: 507-284-3754

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place