Non-Alcoholic Fatty Liver DiseaseGLUSENTICNCT04907721
Development and Evaluation of a Glucagon Sensitivity Test in Individuals With and Without Hepatic Steatosis
A study testing Glucagon Sensitivity test consisting of an amino acid tolerance test and a bolus infusion of glucagon in people with Non-Alcoholic Fatty Liver Disease and Glucagon Resistance, run by University of Copenhagen at 1 site in Denmark.
Trial summary
Glucagon is secreted from pancreatic alpha-cells in response to protein-rich meals and during hypoglycemia. A physiological feedback system exists between the liver and the pancreatic alpha cells termed the liver-alpha cell axis and signifies the role between amino acid-stimulated glucagon secretion and… Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Glucagon Resistance, Type 1 Diabetes
- What is being tested?
- Glucagon Sensitivity test consisting of an amino acid tolerance test and a bolus infusion of glucagon
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteDenmark
- Study dates
- 27 May 2021to 21 Oct 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- BMI = 18.6-25 kg/m2
- Male or female
- 25-65 years of age
- BMI = 25-40 kg/m2
- Male or female
- 25-65 years of age
Show all 11Show fewer
- BMI = 18.6-40 kg/m2
- Male or female
- C-peptide negative
- Insulin pump user
- 25-65 years of age
Who cannot join
- Diabetes (ADA criteria)
- Significant alcohol/drug abuse as per investigators judgement
- Amino acid-related diseases such as phenylketonuria
- Kidney disease
- Cardiac problems
- Cancer within the past 1 year
Show all 40Show fewer
- Severe claustrophobia
- Pacemaker or other non-MR-compatible devices
- Pregnancy or breastfeeding.
- Fib4 score > 3.25.
- Any medicine, acute illness (within the last two weeks) or other circumstances that in the opinion of the investigator might endanger the participants' safety or compliance with the protocol
- Group 2 (overweight and obese individuals)
- Diabetes (ADA criteria)
- Significant alcohol/drug abuse as per investigators judgement
- Amino acid-related diseases such as phenylketonuria
- Kidney disease
- Cardiac problems
- Cancer within the past 1 year
- Severe claustrophobia
- Pacemaker or other non-MR-compatible devices
- Pregnancy or breastfeeding
- Abdominal diameter >70 cm
- Fib4 score > 3.25.
- Any medicine, acute illness (within the last two weeks) or other circumstances that in the opinion of the investigator might endanger the participants' safety or compliance with the protocol
- Group 3 (individuals with type 1 diabetes)
- Type 2 diabetes
- Closed loop user
- Microalbuminuria (30-300 mg/g)
- Significant alcohol/drug abuse as per investigators judgement
- Amino acid-related diseases such as phenylketonuria
- Kidney disease
- Cardiac problems
- Cancer within the past 1 year
- Severe claustrophobia
- Pacemaker or other non-MR-compatible devices
- Pregnancy or breastfeeding
- Abdominal diameter >70 cm
- Fib4 score > 3.25.
- Any medicine, acute illness (within the last two weeks) or other circumstances that in the opinion of the investigator might endanger the participants' safety or compliance with the protocol
- Following inclusion and study completion, our two groups of lean individuals (n=20) and overweight and obese individuals (n=30) will be stratified into two groups based on liver fat content assessed by the magnetic resonance imaging scan. Individuals with <5.6% hepatic steatosis will be allocated to the control group and individuals with ≥5.6% hepatic steatosis to the MASLD group.
Trial locations and contacts
1 site in 1 country.
About this study
Glucagon is secreted from pancreatic alpha-cells in response to protein-rich meals and during hypoglycemia. A physiological feedback system exists between the liver and the pancreatic alpha cells termed the liver-alpha cell axis and signifies the role between amino acid-stimulated glucagon secretion and glucagon-stimulated amino acid metabolism.
Individuals with non-alcoholic fatty liver disease have increased levels of glucagon (hyperglucagonemia) and amino acids (hyperaminoacidemia), which suggests that hepatic steatosis may uncouple glucagon's effect on amino acid metabolism (i.e. reduced glucagon sensitivity). Since hyperglucagonemia contributes to diabetes progression - due to its potentiating effects on hepatic glucose production - hepatic steatosis may create a diabetogenic circle. This study aims to develop and evaluate a test for measuring glucagon sensitivity in humans.
The investigators (Associate Prof. Nicolai J Wewer Albrechtsen and Prof. Jørgen Rungby) will investigate whether amino acid metabolism is attenuated in individuals with hepatic steatosis (assessed by magnetic resonance imaging) due to impaired hepatic glucagon sensitivity and if glucagon's effect on hepatic glucose production is intact compared to individuals without hepatic steatosis suggestive of biased signaling.
Read the detailed description
Amino acids administered orally or intravenously stimulate glucagon secretion from the pancreas and in turn, glucagon is a powerful stimulus for hepatic amino acid turnover through transcriptional (long-term) and non- transcriptional (acute) mechanisms. Several groups including the investigators have linked glucagon secretion to hepatic amino acid metabolism suggesting a mutual feedback cycle, termed the liver-alpha cell axis. A disruption of this axis, which has been shown both pharmacologically using glucagon receptor antagonists and genetically in glucagon receptor knockout mouse models, leads to increased glucagon (hyperglucagonemia) and amino acid (hyperaminoacidemia) concentrations. This phenotype is also evident in subjects with biopsy-verified metabolic dysfunction-associated steatotic liver disease (MASLD) independent of type 2 diabetes suggesting reduced hepatic glucagon sensitivity in the presence of hepatic steatosis. Glucagon increases amino acid catabolism by potentiating ureagenesis, a pathway exclusive to the liver, and hepatic accumulation of triglycerides may reduce glucagon's ability to augment amino acid turnover. Some amino acids are more potent in stimulating glucagon secretion (glucagonotropic amino acids), including alanine, and the glucagon-alanine index is currently used as a surrogate marker for the hepatic actions of glucagon on ureagenesis. The fate of amino acid turnover depends on both glucagon and insulin dynamics by stimulating amino acid catabolism and synthesis, respectively. Studying the effects of glucagon in individuals with type 1 diabetes will allow one to differentiate between the combined effects of glucagon and insulin compared to the effects of glucagon alone.
This study aims to explore hepatic glucagon sensitivity towards amino acid metabolism in individuals with and without hepatic steatosis (based on magnetic resonance imaging (MRI)).
The investigators hypothesize that the effect of endogenous and exogenous glucagon on plasma amino acid levels are impaired in individuals with MASLD (based on hepatic steatosis measured by MRI) compared to controls.
The nomenclature for MASLD has recently been updated from non-alcoholic fatty liver disease (NAFLD) (https://pubmed.ncbi.nlm.nih.gov/37363821/).
- Being tested
- Glucagon Sensitivity test consisting of an amino acid tolerance test and a bolus infusion of glucagon
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 1, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glucagon Sensitivity test consisting of an amino acid tolerance test and a bolus infusion of glucagonDiagnostic test
The test consists of two experimental study days:
Day 1: intravenous bolus-injection of glucagon (0.2 mg at time 0 minutes) evaluating the effect of exogenous glucagon on amino acid disappearance. Blood samples will be obtained from time -10 to 120 minutes.
Day 2: 45-minute intravenous infusion of mixed amino acids (331 mg/min/kg body weight from time 0-45 minutes) to evaluate the effect of endogenous glucagon on amino acid metabolism. Blood samples will be obtained from time -10 to 180 minutes.
All participants will be subjected to a magnetic resonance imaging scan to assess whole-liver steatosis, and a bioelectrical impedance analysis to assess body composition.
Following study inclusion and the magnetic resonance imaging scan, participants will be stratified into groups based on hepatic steatosis. Individuals with <5.6 % hepatic steatosis will be classified as controls and individuals with ≥5.6 % hepatic steatosis will be classified as MASLD.
| Study group | Role | What they receive |
|---|---|---|
| Measuring glucagon sensitivity in humans | Experimental | Participants will be subjected to two experimental days. Receives: Diagnostic Test: Glucagon Sensitivity test consisting of an amino acid tolerance test and a bolus infusion of glucagon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in the calculated GLUSENTIC index between individuals with or without MASLD without diabetes
This index is conceptually be based on the Matsuda/composite index, and will factor in fasting and amino acid-stimulated levels of glucagon and total amino acids using the following formula: 100/(SQRT(Fasting plasma amino acids levels (mean at time -10 and 0 minutes) * Fasting plasma glucagon levels (mean at time -10 and 0 minutes) * Amino acid-stimulated amino acid levels (mean at time 40 and 45 minutes) * Amino acid-stimulated glucagon levels (mean at time 40 and 45 minutes)).
Measured: Time from the first blood sample (at time -10 minutes, following an overnight fast) until the amino acid infusion stops (45 minutes)
Secondary outcomes (23)
Simple linear regression between hepatic steatosis (%) and the GLUSENTIC index
Measurements of hepatic steatosis will be assessed by magnetic resonance imaging. Data from controls and MASLD without diabetes will be included.
Measured: Time from the first blood sample (at time -10 minutes, following an overnight fast) until the amino acid infusion stops (45 minutes)
ROC curve analysis to evaluate cut-off value for GLUSENTIC index
Controls and MASLD groups will be included.
Measured: Time from the first blood sample (at time -10 minutes, following an overnight fast) until the amino acid infusion stops (45 minutes)
Differences in the glucagon-alanine index
The glucagon-alanine index will be measured as previously described: https://pubmed.ncbi.nlm.nih.gov/29305624/. Measurements of hepatic steatosis will be assessed by magnetic resonance imaging. Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: The index will be measured on samples collected after an overnight fast (12 hours)
Differences in plasma levels of amino acids during the amino acid tolerance test (determined by baseline corrected AUC)
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Time from the start of infusion (0 minutes) until time 60 minutes.
Glucagon's ability (exogenous glucagon) to increase amino acid disappearance (determined by baseline corrected AUC or delta) for total amino acid levels and the individual amino acids.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Time from the glucagon injection (time 0 minutes) until time 20 minutes.
Differences in plasma levels of total amino acids and alanine following an overnight fast.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Measured on samples collected after an overnight fast (12 hours)
Baseline corrected AUC for glucagon after a bolus injection of glucagon.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for glucagon during and after the amino acid tolerance test.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made. For insulin and C-peptide measurements, only individuals without diabetes will be compared.
Measured: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Differences in plasma levels of glucagon following an overnight fast.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Measured on samples collected after an overnight fast (12 hours)
Baseline corrected AUC for glucose after a bolus injection of glucagon.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for insulin after a bolus injection of glucagon.
Comparisons between controls and MASLD will be made.
Measured: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for C-peptide after a bolus injection of glucagon.
Comparisons between controls and MASLD will be made.
Measured: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for urea after a bolus injection of glucagon.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for triglycerides after a bolus injection of glucagon.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for glucose during and after the amino acid tolerance test.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Baseline corrected AUC for insulin during and after the amino acid tolerance test.
Comparisons between controls and MASLD will be made.
Measured: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Baseline corrected AUC for C-peptide during and after the amino acid tolerance test.
Comparisons between controls and MASLD and will be made.
Measured: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Baseline corrected AUC for urea during and after the amino acid tolerance test.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Baseline corrected AUC for triglycerides during and after the amino acid tolerance test.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Differences in the formula (plasma urea/plasma amino acids) after the amino acid tolerance test.
Comparisons between controls, MASLD and individuals with type 1 diabetes will be made.
Measured: Time from the amino acid infusion stops (time 45 minutes) until time 180 minutes.
Differences in total and individual amino acids between individuals with overweight or obesity without hepatic steatosis who have been BMI-matched to individuals with hepatic steatosis.
Baseline subtracted AUCs will be made and individuals with or without MASLD, who are matched on BMI in a 1:2 ratio will be compared.
Measured: Time 0-120 minutes on the day of the glucagon injection and time 0-180 minutes on the day of the amino acid tolerance test.
Differences in glucagon between individuals with overweight or obesity without hepatic steatosis who have been BMI-matched to individuals with hepatic steatosis.
Baseline subtracted AUCs will be made and individuals with or without MASLD, who are matched on BMI in a 1:2 ratio will be compared.
Measured: Time time 0-180 minutes on the day of the amino acid tolerance test.
Simple linear regression between the variables, pancreatic steatosis and amino acid stimulated glucagon or insulin levels in individuals without diabetes.
Data from controls and MASLD will be included.
Measured: Pancreatic steatosis and time point 30 minutes on the day of the amino acid tolerance test will be used.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2021
- Study start27 May 2021
- Primary completion21 Oct 2023
- Study completion21 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of CopenhagenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Bispebjerg Hospital, Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Principal investigator, Nicolai Jacob Wewer Albrechtsen, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04907721
- Sponsor's protocol ID
- GLUSENTIC
- Acronym
- GLUSENTIC
- Status last verified
- Oct 2023
- First submitted
- 17 May 2021
- Last updated
- 24 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We have not decided to share IPD as this also would require approval from the ethical and data approval comitee.
Publications
Richter MM, Kemp IM, Heeboll S, Winther-Sorensen M, Kjeldsen SAS, Jensen NJ, Nybing JD, Linden FH, Hogh-Schmidt E, Boesen MP, Madsbad S, Schiodt FV, Norgaard K, Schmidt S, Gluud LL, Haugaard SB, Holst JJ, Nielsen S, Rungby J, Wewer Albrechtsen NJ. Glucagon augments the secretion of FGF21 and GDF15 in MASLD by indirect mechanisms. Metabolism. 2024 Jul;156:155915. doi: 10.1016/j.metabol.2024.155915. Epub 2024 Apr 16.
PubMed 38631460
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development and Evaluation of a Glucagon Sensitivity Test in Individuals With and Without Hepatic Steatosis
- ClinicalTrials.gov ID
- NCT04907721
- Acronym / sponsor ID
- GLUSENTIC / GLUSENTIC
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- Bispebjerg Hospital, Copenhagen University Hospital, Rigshospitalet
- Study start
- 27 May 2021 (actual)
- Primary completion
- 21 Oct 2023 (actual)
- Study completion
- 21 Oct 2023 (actual)
- First posted
- 1 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Glucagon is secreted from pancreatic alpha-cells in response to protein-rich meals and during hypoglycemia. A physiological feedback system exists between the liver and the pancreatic alpha cells termed the liver-alpha cell axis and signifies the role between amino acid-stimulated glucagon secretion and glucagon-stimulated amino acid metabolism.
Individuals with non-alcoholic fatty liver disease have increased levels of glucagon (hyperglucagonemia) and amino acids (hyperaminoacidemia), which suggests that hepatic steatosis may uncouple glucagon's effect on amino acid metabolism (i.e. reduced glucagon sensitivity). Since hyperglucagonemia contributes to diabetes progression - due to its potentiating effects on hepatic glucose production - hepatic steatosis may create a diabetogenic circle. This study aims to develop and evaluate a test for measuring glucagon sensitivity in humans.
The investigators (Associate Prof. Nicolai J Wewer Albrechtsen and Prof. Jørgen Rungby) will investigate whether amino acid metabolism is attenuated in individuals with hepatic steatosis (assessed by magnetic resonance imaging) due to impaired hepatic glucagon sensitivity and if glucagon's effect on hepatic glucose production is intact compared to individuals without hepatic steatosis suggestive of biased signaling.
Detailed description
Amino acids administered orally or intravenously stimulate glucagon secretion from the pancreas and in turn, glucagon is a powerful stimulus for hepatic amino acid turnover through transcriptional (long-term) and non- transcriptional (acute) mechanisms. Several groups including the investigators have linked glucagon secretion to hepatic amino acid metabolism suggesting a mutual feedback cycle, termed the liver-alpha cell axis. A disruption of this axis, which has been shown both pharmacologically using glucagon receptor antagonists and genetically in glucagon receptor knockout mouse models, leads to increased glucagon (hyperglucagonemia) and amino acid (hyperaminoacidemia) concentrations. This phenotype is also evident in subjects with biopsy-verified metabolic dysfunction-associated steatotic liver disease (MASLD) independent of type 2 diabetes suggesting reduced hepatic glucagon sensitivity in the presence of hepatic steatosis. Glucagon increases amino acid catabolism by potentiating ureagenesis, a pathway exclusive to the liver, and hepatic accumulation of triglycerides may reduce glucagon's ability to augment amino acid turnover. Some amino acids are more potent in stimulating glucagon secretion (glucagonotropic amino acids), including alanine, and the glucagon-alanine index is currently used as a surrogate marker for the hepatic actions of glucagon on ureagenesis. The fate of amino acid turnover depends on both glucagon and insulin dynamics by stimulating amino acid catabolism and synthesis, respectively. Studying the effects of glucagon in individuals with type 1 diabetes will allow one to differentiate between the combined effects of glucagon and insulin compared to the effects of glucagon alone.
This study aims to explore hepatic glucagon sensitivity towards amino acid metabolism in individuals with and without hepatic steatosis (based on magnetic resonance imaging (MRI)).
The investigators hypothesize that the effect of endogenous and exogenous glucagon on plasma amino acid levels are impaired in individuals with MASLD (based on hepatic steatosis measured by MRI) compared to controls.
The nomenclature for MASLD has recently been updated from non-alcoholic fatty liver disease (NAFLD) (https://pubmed.ncbi.nlm.nih.gov/37363821/).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Measuring glucagon sensitivity in humans | Experimental | Diagnostic Test: Glucagon Sensitivity test consisting of an amino acid tolerance test and a bolus infusion of glucagonParticipants will be subjected to two experimental days. |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- BMI = 18.6-25 kg/m2
- Male or female
- 25-65 years of age
- BMI = 25-40 kg/m2
- Male or female
Key exclusion criteria (40 listed)
- Diabetes (ADA criteria)
- Significant alcohol/drug abuse as per investigators judgement
- Amino acid-related diseases such as phenylketonuria
- Kidney disease
- Cardiac problems
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glucagon Sensitivity test consisting of an amino acid tolerance test and a bolus infusion of glucagonThe test consists of two experimental study days: Day 1: intravenous bolus-injection of glucagon (0.2 mg at time 0 minutes) evaluating the effect of exogenous glucagon on amino acid disappearance. Blood samples will be obtained from time -10 to 120 minutes. Day 2: 45-minute intravenous infusion of mixed amino acids (331 mg/min/kg body weight from time 0-45 minutes) to evaluate the effect of endogenous glucagon on amino acid metabolism. Blood samples will be obtained from time -10 to 180 minutes. All participants will be subjected to a magnetic resonance imaging scan to assess whole-liver steatosis, and a bioelectrical impedance analysis to assess body composition. Following study inclusion and the magnetic resonance imaging scan, participants will be stratified into groups based on hepatic steatosis. Individuals with <5.6 % hepatic steatosis will be classified as controls and individuals with ≥5.6 % hepatic steatosis will be classified as MASLD. | Diagnostic test | Measuring glucagon sensitivity in humans |
Primary outcome
Differences in the calculated GLUSENTIC index between individuals with or without MASLD without diabetes
Time frame: Time from the first blood sample (at time -10 minutes, following an overnight fast) until the amino acid infusion stops (45 minutes)
This index is conceptually be based on the Matsuda/composite index, and will factor in fasting and amino acid-stimulated levels of glucagon and total amino acids using the following formula: 100/(SQRT(Fasting plasma amino acids levels (mean at time -10 and 0 minutes) * Fasting plasma glucagon levels (mean at time -10 and 0 minutes) * Amino acid-stimulated amino acid levels (mean at time 40 and 45 minutes) * Amino acid-stimulated glucagon levels (mean at time 40 and 45 minutes)).
23 secondary outcomes
Simple linear regression between hepatic steatosis (%) and the GLUSENTIC index
Time frame: Time from the first blood sample (at time -10 minutes, following an overnight fast) until the amino acid infusion stops (45 minutes)
ROC curve analysis to evaluate cut-off value for GLUSENTIC index
Time frame: Time from the first blood sample (at time -10 minutes, following an overnight fast) until the amino acid infusion stops (45 minutes)
Differences in the glucagon-alanine index
Time frame: The index will be measured on samples collected after an overnight fast (12 hours)
Differences in plasma levels of amino acids during the amino acid tolerance test (determined by baseline corrected AUC)
Time frame: Time from the start of infusion (0 minutes) until time 60 minutes.
Glucagon's ability (exogenous glucagon) to increase amino acid disappearance (determined by baseline corrected AUC or delta) for total amino acid levels and the individual amino acids.
Time frame: Time from the glucagon injection (time 0 minutes) until time 20 minutes.
Differences in plasma levels of total amino acids and alanine following an overnight fast.
Time frame: Measured on samples collected after an overnight fast (12 hours)
Baseline corrected AUC for glucagon after a bolus injection of glucagon.
Time frame: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for glucagon during and after the amino acid tolerance test.
Time frame: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Differences in plasma levels of glucagon following an overnight fast.
Time frame: Measured on samples collected after an overnight fast (12 hours)
Baseline corrected AUC for glucose after a bolus injection of glucagon.
Time frame: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for insulin after a bolus injection of glucagon.
Time frame: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for C-peptide after a bolus injection of glucagon.
Time frame: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for urea after a bolus injection of glucagon.
Time frame: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for triglycerides after a bolus injection of glucagon.
Time frame: Time from the glucagon injection (time 0 minutes) until time 120 minutes.
Baseline corrected AUC for glucose during and after the amino acid tolerance test.
Time frame: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Baseline corrected AUC for insulin during and after the amino acid tolerance test.
Time frame: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Baseline corrected AUC for C-peptide during and after the amino acid tolerance test.
Time frame: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Baseline corrected AUC for urea during and after the amino acid tolerance test.
Time frame: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Baseline corrected AUC for triglycerides during and after the amino acid tolerance test.
Time frame: Time from the amino acid infusion starts (time 0 minutes) until time 180 minutes.
Differences in the formula (plasma urea/plasma amino acids) after the amino acid tolerance test.
Time frame: Time from the amino acid infusion stops (time 45 minutes) until time 180 minutes.
Differences in total and individual amino acids between individuals with overweight or obesity without hepatic steatosis who have been BMI-matched to individuals with hepatic steatosis.
Time frame: Time 0-120 minutes on the day of the glucagon injection and time 0-180 minutes on the day of the amino acid tolerance test.
Differences in glucagon between individuals with overweight or obesity without hepatic steatosis who have been BMI-matched to individuals with hepatic steatosis.
Time frame: Time time 0-180 minutes on the day of the amino acid tolerance test.
Simple linear regression between the variables, pancreatic steatosis and amino acid stimulated glucagon or insulin levels in individuals without diabetes.
Time frame: Pancreatic steatosis and time point 30 minutes on the day of the amino acid tolerance test will be used.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2023.
- Derived from this study: PubMed 38631460Richter MM, Kemp IM, Heeboll S, Winther-Sorensen M, Kjeldsen SAS, Jensen NJ, Nybing JD, Linden FH, Hogh-Schmidt E, Boesen MP, Madsbad S, Schiodt FV, Norgaard K, Schmidt S, Gluud LL, Haugaard SB, Holst JJ, Nielsen S, Rungby J, Wewer Albrechtsen NJ. Glucagon augments the secretion of FGF21 and GDF15 in MASLD by indirect mechanisms. Metabolism. 2024 Jul;156:155915. doi: 10.1016/j.metabol.2024.155915. Epub 2024 Apr 16.
- Individual participant dataSharing planned: No. We have not decided to share IPD as this also would require approval from the ethical and data approval comitee.
Related trials for Non-Alcoholic Fatty Liver Disease
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
RecruitingPhase 2
A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) Due to MASH
Metabolic Dysfunction-Associated Steatohepatitis, Non-alcoholic Fatty Liver Disease
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
Active, not recruiting
Target of Suv420h1/2 in Hepatocytes
NAFLD
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Glucagon Sensitivity test consisting of an amino acid tolerance test and a bolus infusion of glucagon in people with Non-Alcoholic Fatty Liver Disease and Glucagon Resistance, run by University of Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in the calculated GLUSENTIC index between individuals with or without MASLD without diabetes (time frame: Time from the first blood sample (at time -10 minutes, following an overnight fast) until the amino acid infusion stops (45 minutes)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04907721, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2023; AzTrials last refreshed its copy on 6 Nov 2026.