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Trial · Interventional

CompletedPhase 1/2Results postedRegistry data

The Effects of Glucagon on Hepatic Metabolism

NCTNCT05500586 (opens ClinicalTrials.gov in a new tab)Other id22-000113Other idR01DK116231

Overview

Status
Completed
Phase
Phase 1/2
Enrollment
21 participants (actual)
Sponsor
Adrian Vella · Other
Design
Not randomized · Open label (no masking)
Countries
1 country

United States

Start
20 Oct 2022
Primary completion
30 Sept 2025
Completion
31 Mar 2026
First posted
15 Aug 2022
Last update posted
14 Oct 2026
Conditions
Obesity · Type2diabetes · NAFLD

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
202220232024202520262027
  1. Ph 1/2

    The Effects of Glucagon on Hepatic Metabolism

    NCT05500586

    20 Oct 2022 to 31 Mar 2026

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

Whether impaired postprandial glucagon suppression in prediabetes and T2DM is an attempt to overcome resistance to glucagon's actions on hepatic AA catabolism, a defect in α-cell function, or a combination of both are important, unanswered questions. NAFLD is associated with T2DM risk and impaired insulin action. Unfortunately, it is unclear if glucagon resistance is caused by obesity, hepatic steatosis or both. The experiments outlined will determine if glucagon's actions on hepatic amino acid catabolism and EGP interact with hepatic lipid metabolism in lean and obese subjects with and without T2DM (and with varying degrees of hepatic steatosis).

Interventions

  • Glucagon response studyDrug

Arms5

  • Experimental

    Healthy Adults

    We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.

  • Experimental

    Obese Adults Protein Density Fat Fraction (PDFF) < 5%

    We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.

  • Experimental

    Adults with Type 2 Diabetes Protein Density Fat Fraction (PDFF) < 5%

    We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.

  • Experimental

    Adults with Type 2 Diabetes Protein Density Fat Fraction (PDFF) > 5%

    We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.

  • Experimental

    Obese Adults Protein Density Fat Fraction (PDFF) > 5%

    We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Rate of Amino Acid Catabolism in the Presence / Absence of Glucagon

    Time frame · 0 minutes, 120 minutes, 240 minutes

    Registry description

    Amino acid catabolism assessed by leucine reamination, a surrogate measure of leucine oxidation, during fasting (0 minutes), intermediate glucagon infusion (120 minutes), and high glucagon infusion (240 minutes).

Secondary outcomes(3)
  1. Effect of Diabetes on Amino-acid Catabolism

    Time frame · 240 minutes of study

    Registry description

    Tracer-dependent measurement of amino-acid clearance

  2. Splanchnic Balance of Essential Amino Acids During Fasting and Glucagon Infusion

    Time frame · 0 Minutes, 120 Minutes, 240 Minutes

    Registry description

    Splanchnic balance of essential amino acids calculated from the arteriovenous concentration difference across the liver multiplied by splanchnic blood flow. Measurements were obtained during fasting (0 minutes), intermediate glucagon infusion (120 minutes), and high glucagon infusion (240 minutes) to evaluate the effect of obesity and hepatic steatosis on glucagon-mediated amino acid metabolism.

  3. Splanchnic Balance of Nonessential Amino Acids During Fasting and Glucagon Infusion

    Time frame · 0 Minutes, 120 Minutes, 240 Minutes

    Registry description

    Splanchnic balance of nonessential amino acids calculated from the arteriovenous concentration difference across the liver multiplied by splanchnic blood flow. Measurements were obtained during fasting (0 minutes), intermediate glucagon infusion (120 minutes), and high glucagon infusion (240 minutes) to evaluate the effect of obesity and hepatic steatosis on glucagon-mediated amino acid metabolism.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· 0 minutes, 120 minutes, 240 minutes

Rate of Amino Acid Catabolism in the Presence / Absence of Glucagon

GroupValue (mmol/min)Spread
Healthy Adults172
Obese Adults Protein Density Fat Fraction (PDFF) < 5%265
Obese Subjects Protein Density Fat Fraction (PDFF) > 5%206
Adults With Type 2 Diabetes Protein Density Fat Fraction (PDFF) < 5%not posted–
Adults With Type 2 Diabetes Protein Density Fat Fraction (PDFF) > 5%not posted–
Secondary and other outcome results(3)
Secondary outcome· 240 minutes of study

Effect of Diabetes on Amino-acid Catabolism

GroupValue
Healthy Adultsnot posted
Obese Adults Protein Density Fat Fraction (PDFF) < 5%not posted
Adults With Type 2 Diabetes Protein Density Fat Fraction (PDFF) < 5%not posted
Adults With Type 2 Diabetes Protein Density Fat Fraction (PDFF) > 5%not posted
Obese Adults Protein Density Fat Fraction (PDFF) > 5%not posted
Secondary outcomeMean· 0 Minutes, 120 Minutes, 240 Minutes

Splanchnic Balance of Essential Amino Acids During Fasting and Glucagon Infusion

GroupValue (nmol/min)Spread
Healthy Adults1.15.3
Obese Adults Protein Density Fat Fraction (PDFF) < 5%2.02.3
Obese Subjects Protein Density Fat Fraction (PDFF) > 5%0.53.0
Adults With Type 2 Diabetes Protein Density Fat Fraction (PDFF) < 5%not posted–
Adults With Type 2 Diabetes Protein Density Fat Fraction (PDFF) > 5%not posted–
Secondary outcomeMean· 0 Minutes, 120 Minutes, 240 Minutes

Splanchnic Balance of Nonessential Amino Acids During Fasting and Glucagon Infusion

GroupValue (nmol/min)Spread
Healthy Adults-2.19.0
Obese Adults Protein Density Fat Fraction (PDFF) < 5%13.84.5
Adults With Type 2 Diabetes Protein Density Fat Fraction (PDFF) < 5%5.74.8
Adults With Type 2 Diabetes Protein Density Fat Fraction (PDFF) > 5%not posted–
Obese Adults Protein Density Fat Fraction (PDFF) > 5%not posted–

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Healthy AdultsWe will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon. Glucagon response study: Please see information in group descriptions0 / 70 / 76 / 7
Obese Adults Protein Density Fat Fraction (PDFF) < 5%We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon. Glucagon response study: Please see information in group descriptions0 / 60 / 66 / 6
Obese Adults Protein Density Fat Fraction (PDFF) > 5%We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon. Glucagon response study: Please see information in group descriptions0 / 70 / 76 / 7
Adults With Type 2 Diabetes Protein Density Fat Fraction (PDFF) < 5%We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon. Glucagon response study: Please see information in group descriptions0 / 00 / 00 / 0
Adults With Type 2 Diabetes Protein Density Fat Fraction (PDFF) > 5%We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon. Glucagon response study: Please see information in group descriptions0 / 00 / 00 / 0

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 25 Years up to 65 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria - Obese Subjects with Type 2 Diabetes: * Type 2 diabetes * BMI ≥ 28 Kg/M2 * Managed by diet alone or a combination of metformin and/or sulfonylurea * Willing to stop glucose-lowering medication for 3 weeks prior to participation and willing to self-monitor their fasting glucose during this time * No history of micro- or macrovascular complications of T2DM Exclusion Criteria - Obese Subjects with Type 2 Diabetes: * Age \< 25 or \> 65 years * HbA1c ≥ 8.5% * BMI ≤ 28 Kg/M2 * 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. * Known contraindications to MRI * Hematocrit \< 35% * History of uncontrolled thyroid disease * Consumption of \> 2 alcohol drinks per day or \> 14 per week or a positive AUDIT questionnaire. * Allergy to iodine * Thrombocytopenia, history of bleeding disorder or use of anticoagulation * Subjects with treatment change or significant weight change (≥ 10%) in the prior 3 months. Inclusion Criteria - Obese subjects without Type 2 Diabetes: -Obese subjects without type 2 diabetes but are age, sex and weight-matched (BMI ≥ 28 Kg/M2) with subjects who have T2DM Exclusion Criteria - Obese Subjects without Type 2 Diabetes: * Age \< 25 or \> 65 years (match subjects with T2DM) * HbA1c ≥ 6.5% * BMI ≤ 28 Kg/M2 * Use of any glucose-lowering agents * 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. * Known contraindications to MRI * Hematocrit \< 35% * History of uncontrolled thyroid disease. * Consumption of \> 2 alcohol drinks per day or \> 14 per week or a positive AUDIT questionnaire. * Allergy to iodine * Thrombocytopenia, history of bleeding disorder or use of anticoagulation Inclusion Criteria - Lean subjects without Diabetes: -Subjects who do not have type 2 diabetes but are age and sex but are not weight-matched (BMI ≤ 25 Kg/M2) with subjects who have T2DM Exclusion Criteria - Lean subjects without Diabetes: * Age \< 25 or \> 65 years (match subjects with T2DM) * HbA1c ≥ 6.5% * BMI ≥ 25 Kg/M2 unless % body fat is \< 20% in males and \< 30% in females. * Use of any glucose-lowering agents * 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. * Known contraindications to MRI * Hematocrit \< 35% * History of uncontrolled thyroid disease. * 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. * Allergy to iodine * Thrombocytopenia, history of bleeding disorder or use of anticoagulation

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