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Glucagon Suppression by Hyperglycemia in the Presence and Absence of Amino Acid Infusion

Primary Purpose

Healthy, Type 2 Diabetes, Obesity

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Dextrose

Clinisol 15%

About this trial

This is an interventional basic science trial for Healthy

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria - Obese Subjects with Type 2 Diabetes:

HbA1c ≤ 8.5% (type 2 diabetic subjects).
HbA1c ≤ 6.5% (obese and lean subjects).
BMI ≥ 28 Kg/M^2 (Obese subjects with and without type 2 diabetes).
BMI ≤ 25 Kg/M^2 (Lean subjects without type 2 diabetes).
Use of sulfonylureas or metformin only (type 2 diabetec subjects).
For female subjects: negative pregnancy test at the time of enrollment or study.
No history of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
No active systemic illness or malignancy.
No symptomatic macrovascular or microvascular disease.
No contraindications to MRI (e.g., metal implants, claustrophobia).
Hematocrit > 35%.
TSH > 0.4 or < 5.5.
Consumption of < 2 alcohol drinks per day or < 14 per week or a negative AUDIT questionnaire.

Exclusion Criteria - Obese Subjects with Type 2 Diabetes:

HbA1c ³ 8.5%
BMI ≤ 28 Kg/M2
Use of insulin or agents other than sulfonylureas or metformin.
For female subjects: positive pregnancy test at the time of enrollment or study
History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
Active systemic illness or malignancy.
Symptomatic macrovascular or microvascular disease.
Contraindications to MRI (e.g., metal implants, claustrophobia).
Hematocrit < 35%
TSH < 0.4 or > 5.5.
Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire.

Inclusion Criteria - Obese Subjects without Type 2 Diabetes:

BMI ≥ 28 Kg/M2.
> 5% liver fat content, as determined by MRI using the proton density fat fraction (PDFF) technique.

Exclusion Criteria - Obese Subjects without Type 2 Diabetes:

HbA1c ≥ 6.5%
BMI ≤ 28 Kg/M2
Use of any glucose-lowering agents including metformin or sulfonylureas.
For female subjects: positive pregnancy test at the time of enrollment or study
History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
Active systemic illness or malignancy.
Symptomatic macrovascular or microvascular disease.
Contraindications to MRI (e.g., metal implants, claustrophobia).
Hematocrit < 35%
TSH < 0.4 or > 5.5.
Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire.

Inclusion Criteria - Lean subjects without Diabetes:

- BMI ≤ 25 Kg/M^2).

Exclusion Criteria - Lean Subjects without Diabetes:

HbA1c ≥ 6.5%.
BMI ≥ 25 Kg/M^2.
Use of any glucose-lowering agents including metformin or sulfonylureas.
For female subjects: positive pregnancy test at the time of enrollment or study.
History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
Active systemic illness or malignancy.
Symptomatic macrovascular or microvascular disease.
Contraindications to MRI (e.g., metal implants, claustrophobia).
Hematocrit < 35%.
TSH < 0.4 or > 5.5.
Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire.
Liver fat content ≥ 5% as determined by MRI using the proton density fat fraction (PDFF) technique.

Sites / Locations

Mayo Clinic RochesterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Healthy Adults, Obese Adults, Adults with Type 2 diabetes: Saline and Glucose

Healthy Adults, Obese Adults, Adults with Type 2 diabetes: Amino Acid and Glucose

Arm Description

Study visit: Subjects will receive a caffeine free, standardized evening meal and remain fasting overnight. An IV infusion of saline and glucose (50%) will be given the next morning and continue until the end of study. Blood draws will be collected frequently from the IV line to monitor blood glucose levels.

Study visit: Subjects will receive a caffeine free, standardized evening meal and remain fasting overnight. An IV infusion of glucose (50%) will be given the next morning together with an IV infusion of Clinisol 15% (an amino acid mixture) will be given the next morning and continue until the end of study. Blood draws will be collected frequently from the IV line to monitor blood glucose levels.

Outcomes

Primary Outcome Measures

Change in Glucagon Suppression (G50) caused by amino acids vs. saline

concentration of glucose necessary to suppress glucagon by 50%

Secondary Outcome Measures

Glucagon suppression (G50) is greater in people with T2DM

concentration of glucose necessary to suppress glucagon by 50%

glucagon suppression (G50) is greater in obese compared to lean people without T2DM

concentration of glucose necessary to suppress glucagon by 50%

Full Information

NCT ID

NCT05264727

First Posted

February 22, 2022

Last Updated

May 30, 2023

Sponsor

Mayo Clinic

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT05264727

Brief Title

Glucagon Suppression by Hyperglycemia in the Presence and Absence of Amino Acid Infusion

Official Title

Glucagon Suppression by Hyperglycemia in the Presence and Absence of Amino Acid Infusion

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

May 30, 2023 (Actual)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

This study is being done to better understand how amino acids alter the release of glucagon and insulin compared to glucose alone in health and disease.

Detailed Description

T2DM and prediabetes are characterized by abnormal post-prandial suppression of glucagon, which contributes to postprandial hyperglycemia by increasing endogenous glucose production (EGP). In rodents, altered glucagon signaling changes α-cell function and mass - an effect mediated by changes in circulating AA concentrations. Are the elevated concentrations of branched-chain AA and other AA metabolites in T2DM a cause or an effect of global α-cell dysfunction? To measure glucagon secretion, as well as glucagon action, we have developed a population model of glucagon kinetics allowing us to deconvolve secretion from glucagon concentrations in a manner similar to Van Cauter's model for insulin secretion from C-peptide. This enables better characterization of α-cell function in humans. In addition to our novel methodology, we can characterize α-cell responsiveness to a graded glucose infusion, by quantifying (G50) - the change in glucose concentration necessary to suppress glucagon secretion by 50%. These experiments will determine if the glucagon secretion in response to AA differs in obese individuals with T2DM from that observed in obese individuals without T2DM.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy, Type 2 Diabetes, Obesity

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Healthy Adults, Obese Adults, Adults with Type 2 diabetes: Saline and Glucose

Arm Type

Experimental

Arm Description

Arm Title

Healthy Adults, Obese Adults, Adults with Type 2 diabetes: Amino Acid and Glucose

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Dextrose

Intervention Description

Intravenous graded glucose infusion using 50% dextrose will commence at 1mg/kg/min and increase to 2 (0900), 4 (1000) and 8mg/kg/min (1100) every 60 minutes

Intervention Type

Drug

Intervention Name(s)

Clinisol 15%

Other Intervention Name(s)

Amino Acid Mixture

Intervention Description

Intravenous infusion 0.003ml/kg/min infused from 0 to 240 minutes

Primary Outcome Measure Information:

Title

Change in Glucagon Suppression (G50) caused by amino acids vs. saline

Description

concentration of glucose necessary to suppress glucagon by 50%

Time Frame

240 minutes of study

Secondary Outcome Measure Information:

Title

Glucagon suppression (G50) is greater in people with T2DM

Description

concentration of glucose necessary to suppress glucagon by 50%

Time Frame

240 minutes of study

Title

glucagon suppression (G50) is greater in obese compared to lean people without T2DM

Description

concentration of glucose necessary to suppress glucagon by 50%

Time Frame

240 minutes of study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria - Obese Subjects with Type 2 Diabetes: HbA1c ≤ 8.5% (type 2 diabetic subjects). HbA1c ≤ 6.5% (obese and lean subjects). BMI ≥ 28 Kg/M^2 (Obese subjects with and without type 2 diabetes). BMI ≤ 25 Kg/M^2 (Lean subjects without type 2 diabetes). Use of sulfonylureas or metformin only (type 2 diabetec subjects). For female subjects: negative pregnancy test at the time of enrollment or study. No history of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy. No active systemic illness or malignancy. No symptomatic macrovascular or microvascular disease. No contraindications to MRI (e.g., metal implants, claustrophobia). Hematocrit > 35%. TSH > 0.4 or < 5.5. Consumption of < 2 alcohol drinks per day or < 14 per week or a negative AUDIT questionnaire. Exclusion Criteria - Obese Subjects with Type 2 Diabetes: HbA1c ³ 8.5% BMI ≤ 28 Kg/M2 Use of insulin or agents other than sulfonylureas or metformin. For female subjects: positive pregnancy test at the time of enrollment or study History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy. Active systemic illness or malignancy. Symptomatic macrovascular or microvascular disease. Contraindications to MRI (e.g., metal implants, claustrophobia). Hematocrit < 35% TSH < 0.4 or > 5.5. Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire. Inclusion Criteria - Obese Subjects without Type 2 Diabetes: BMI ≥ 28 Kg/M2. > 5% liver fat content, as determined by MRI using the proton density fat fraction (PDFF) technique. Exclusion Criteria - Obese Subjects without Type 2 Diabetes: HbA1c ≥ 6.5% BMI ≤ 28 Kg/M2 Use of any glucose-lowering agents including metformin or sulfonylureas. For female subjects: positive pregnancy test at the time of enrollment or study History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy. Active systemic illness or malignancy. Symptomatic macrovascular or microvascular disease. Contraindications to MRI (e.g., metal implants, claustrophobia). Hematocrit < 35% TSH < 0.4 or > 5.5. Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire. Inclusion Criteria - Lean subjects without Diabetes: - BMI ≤ 25 Kg/M^2). Exclusion Criteria - Lean Subjects without Diabetes: HbA1c ≥ 6.5%. BMI ≥ 25 Kg/M^2. Use of any glucose-lowering agents including metformin or sulfonylureas. For female subjects: positive pregnancy test at the time of enrollment or study. History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy. Active systemic illness or malignancy. Symptomatic macrovascular or microvascular disease. Contraindications to MRI (e.g., metal implants, claustrophobia). Hematocrit < 35%. TSH < 0.4 or > 5.5. Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire. Liver fat content ≥ 5% as determined by MRI using the proton density fat fraction (PDFF) technique.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Adrian Vella, MD

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jeanette Laugen

Phone

507-255-8110

Laugen.Jeanette@mayo.edu

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

https://www.mayo.edu/research/clinical-trials

Description

Mayo Clinic Clinical Trials

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Glucagon Suppression by Hyperglycemia in the Presence and Absence of Amino Acid Infusion

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