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| ID | Type | Description | Link |
|---|---|---|---|
| 5R01DK126206-03 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in the control of blood sugar level by enhancing insulin secretion from the pancreas after eating a meal. The purpose of this research study is to evaluate the role of GLP1R in the response to elevated glucagon concentrations.
Glucagon within the islet can signal the β-cell through GLP1R, and acts as an insulin secretagogue. This signaling is blocked by exendin-9,39. The relative importance of glucagon signaling through its cognate receptor or through GLP1R is unknown. Despite the lower affinity of GLP1R for glucagon, intra-islet concentrations of glucagon are sufficiently high to stimulate GLP1R. The other situation where this may occur is in response to pharmacologic doses of glucagon as used for β-cell function testing or raising peripheral glucagon concentrations above fasting values. The experiments proposed will characterize the role of GLP1R in glucagon's actions on the β-cell and the potential therapeutic role of dual (GLP-1R and glucagon receptor) agonists for the treatment of T2DM and obesity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Saline, Then Exendin-9,39 | Experimental | A week or two after screening, participants were admitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. |
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| Exendin-9,39, Then Saline | Experimental | A week or two after screening, participants were admitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exendin-9,39 | Biological | Exendin-9,39 is a competitive antagonist of GLP-1 actions at the GLP-1 receptor |
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| Measure | Description | Time Frame |
|---|---|---|
| Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion | 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). | Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Adrian Vella, MD | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
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| Label | URL |
|---|---|
| Mayo Clinic Clinical Trials | View source |
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None of the enrolled subjects were excluded and all were randomized
Healthy volunteers responded to intramural advertising at the Mayo Clinic between March 2021 and September 2021
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Subjects without diabetes to enable evaluation of insulin secretory capacity
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants were randomized to receive all interventions |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion | 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). | Posted | Mean | Standard Error | nmol/min per 300 min | Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study |
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Time between screening and completion of the study = 6 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Saline infusion is started at time 0 and continues for 300 minutes. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infusion line lost | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Phlebitis |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Adrian Vella | Mayo Clinic | 507-284-3754 | vella.adrian@mayo.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 26, 2020 | Mar 15, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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| Saline | Other | Placebo comparator |
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| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| OG001 | Insulin Secretion During the Exendin-9,39 Study | 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. |
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|
|
| 0 |
| 11 |
| 0 |
| 11 |
| 2 |
| 11 |
| EG001 | 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. Exendin-9,39 infusion is started at time 0 and continues for 300 minutes. | 0 | 11 | 0 | 11 | 0 | 11 |
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| Nausea | Gastrointestinal disorders | Non-systematic Assessment | Nausea with glucagon infusion |
|
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| D017670 |
| Sodium Compounds |