Non-Alcoholic Fatty Liver DiseaseNCT04859322
The Effect of Lifestyle-induced Hepatic Steatosis on Glucagon-stimulated Amino Acid Turnover
A study testing Glucagon in people with Non-Alcoholic Fatty Liver Disease and Glucagon Resistance, run by Malte Palm Suppli, MD at 1 site in Denmark.
Trial summary
Many patients with type 2 diabetes exhibit elevated plasma concentrations of the glucose-mobilising pancreatic hormone glucagon; i.e. hyperglucagonaemia. This contributes to the hyperglycaemic state of the patients and is considered an important component in the pathophysiology of type 2 diabetes; but the mechanisms… Read more about this study
- Who is it for?
- Ages 20 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Glucagon Resistance
- What is being tested?
- Glucagon
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- 8 Feb 2021to 9 Dec 2021
- 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 20 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Normal fasting plasma glucose and glycated haemoglobin (HbA1c) <42 mmol/mol
- Body mass index (BMI) between 18.5 and 25 kg/m2
- Haemoglobin >8.3 mmol/l
- Habitual diet in accordance with the Nordic Nutrition Recommendations
- Age between 20 and 65 years
- Oral and written informed consent
Who cannot join
- Diabetes
- First-degree relatives with diabetes
- Fasting plasma triacylglycerol indicating dyslipidemia (≥2 mmol/l)
- Nephropathy (estimated glomerular filtration rate (eGFR) <60 ml/min and/or microalbuminuria with an albumin to creatinine ratio of 30-300 μg/mg)
- Known liver disease and/or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2 × normal values
- Signs of liver fibrosis and/or steatosis evaluated by FibroScan (CAP value >2380 dB/m and/or kPa >65.0) and/or FIB-4 score (>1.45)
Show all 13Show fewer
- >5% steatosis evaluated by MRI carried out before experimental Day A (see Methods)
- Use of medication
- Use of dietary protein supplementation or any other dietary supplements that cannot be paused during participation
- Excessive training habits, defined as >2 weekly strength and/or aerobic training sessions
- Pregnancy and/or breastfeeding
- Implanted metal objects incompatible with magnetic resonance imaging (MRI)
- Any condition that the investigator feels would interfere with trial completion
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Clinical Metabolic Research
Hellerup, Copenhagen, 2900
About this study
Many patients with type 2 diabetes exhibit elevated plasma concentrations of the glucose-mobilising pancreatic hormone glucagon; i.e. hyperglucagonaemia. This contributes to the hyperglycaemic state of the patients and is considered an important component in the pathophysiology of type 2 diabetes; but the mechanisms underlying this phenomenon remain unclear. The liver constitutes the main target organ of glucagon, and studies have shown that hyperglucagonaemia goes hand in hand with hyperaminoacidaemia and that both are associated with non-alcoholic fatty liver disease (NAFLD), independently of the presence of type 2 diabetes. In line with this, several recent studies support the existence of a feedback-cycle between the liver and the pancreatic alpha cells, governed by circulating glucagon and amino acids. The investigators hypothesise that the presence of hepatic steatosis results in hepatic glucagon resistance at the level of amino acid turnover, i.e. impaired glucagon-induced suppression of circulating amino acid concentrations. If this hypothesis proves correct, it would establish build-up of fat in the liver as a core mechanism underlying hyperglucagonaemia and, since the hyperglucagonemia is at least partly responsible for the fasting hyperglycaemia, as an important contributor to the hyperglycaemia of type 2 diabetes.
- Being tested
- Glucagon
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucagonDrug
Also called Insulin, Somatostatin, 6,6 H2-glucose
Pancreatic clamp
| Study group | Role | What they receive |
|---|---|---|
| Healthy Participants | Experimental | 20 healthy participants included in the arm for 3 experimental days each. On each experimental day infusions of stable isotope glucose (0,6 micromol/kg/min), glucagon (1 hour low; 0,6 ng/kg/min, 2 hours high; 4,0 ng/kg/min), somatostatin (450 micrograms/hour) and insulin (0,1 mU/kg/min) will be administered. Between the first two experimental days the participants will follow a sedentary lifestyle combined with a high-calorie diet intervention Receives: Drug: Glucagon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nadir of the total amino acid concentration during a two-hour high physiological glucagon infusion during a pancreatic clamp with somatostatin
micromol/liter
Measured: depending on the nadir between time 60 minutes and time 180 minutes
Secondary outcomes (3)
average slope of the curve describing the change in the total amino acid concentration during 'supraphysiological' glucagon infusion
micromol/liter/minute
Measured: between time 60 minutes and time 180 minutes
the incremental area under the curve (iAUC) for total amino acid concentrations during 'supraphysiological' glucagon infusion
micromol/liter
Measured: between time 60 minutes and time 180 minutes
the percentage change in amino acid concentration during the last hour of the 'supraphysiological' glucagon infusion as assessed by baseline subtracted AUC
micromol/liter
Measured: between time 60 minutes and time 180 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2021
- Study start8 Feb 2021
- Primary completion9 Dec 2021
- Study completion9 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Malte Palm Suppli, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark, Copenhagen University Hospital, Rigshospitalet, Department of Biomedical Sciences & NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health, and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Responsible party
- Sponsor-investigator, Malte Palm Suppli, MD, University Hospital, Gentofte, Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04859322
- Sponsor's protocol ID
- SIRG-2
- Status last verified
- May 2023
- First submitted
- 21 Apr 2021
- Last updated
- 11 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Nagele NS, Suppli MP, Gilliam-Vigh H, Petersen N, Hartmann B, Knop FK, Lund AB, Jensen BAH. Short term overfeeding disrupts small intestinal barrier integrity and activates hepatic immunity in healthy men. iScience. 2026 Sep 22;29(10):117724. doi: 10.1016/j.isci.2026.117724. eCollection 2026 Oct 16.
PubMed 42866259Suppli MP, Hogedal A, Bagger JI, Chabanova E, van Hall G, Forman JL, Christensen MB, Albrechtsen NJW, Holst JJ, Knop FK. Signs of Glucagon Resistance After a 2-Week Hypercaloric Diet Intervention. J Clin Endocrinol Metab. 2024 Mar 15;109(4):955-967. doi: 10.1210/clinem/dgad666.
PubMed 37967235
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Lifestyle-induced Hepatic Steatosis on Glucagon-stimulated Amino Acid Turnover
- ClinicalTrials.gov ID
- NCT04859322
- Acronym / sponsor ID
- SIRG-2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Malte Palm Suppli, MDUniversity, hospital or other
- Collaborators
- Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark, Copenhagen University Hospital, Rigshospitalet, Department of Biomedical Sciences & NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health, and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Study start
- 8 Feb 2021 (actual)
- Primary completion
- 9 Dec 2021 (actual)
- Study completion
- 9 Dec 2021 (actual)
- First posted
- 26 Apr 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.
Many patients with type 2 diabetes exhibit elevated plasma concentrations of the glucose-mobilising pancreatic hormone glucagon; i.e. hyperglucagonaemia. This contributes to the hyperglycaemic state of the patients and is considered an important component in the pathophysiology of type 2 diabetes; but the mechanisms underlying this phenomenon remain unclear. The liver constitutes the main target organ of glucagon, and studies have shown that hyperglucagonaemia goes hand in hand with hyperaminoacidaemia and that both are associated with non-alcoholic fatty liver disease (NAFLD), independently of the presence of type 2 diabetes. In line with this, several recent studies support the existence of a feedback-cycle between the liver and the pancreatic alpha cells, governed by circulating glucagon and amino acids. The investigators hypothesise that the presence of hepatic steatosis results in hepatic glucagon resistance at the level of amino acid turnover, i.e. impaired glucagon-induced suppression of circulating amino acid concentrations. If this hypothesis proves correct, it would establish build-up of fat in the liver as a core mechanism underlying hyperglucagonaemia and, since the hyperglucagonemia is at least partly responsible for the fasting hyperglycaemia, as an important contributor to the hyperglycaemia of type 2 diabetes.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy Participants | Experimental | Drug: Glucagon20 healthy participants included in the arm for 3 experimental days each. On each experimental day infusions of stable isotope glucose (0,6 micromol/kg/min), glucagon (1 hour low; 0,6 ng/kg/min, 2 hours high; 4,0 ng/kg/min), somatostatin (450 micrograms/hour) and insulin (0,1 mU/kg/min) will be administered. Between the first two experimental days the participants will follow a sedentary lifestyle combined with a high-calorie diet intervention |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Normal fasting plasma glucose and glycated haemoglobin (HbA1c) <42 mmol/mol
- Body mass index (BMI) between 18.5 and 25 kg/m2
- Haemoglobin >8.3 mmol/l
- Habitual diet in accordance with the Nordic Nutrition Recommendations
- Age between 20 and 65 years
Key exclusion criteria (13 listed)
- Diabetes
- First-degree relatives with diabetes
- Fasting plasma triacylglycerol indicating dyslipidemia (≥2 mmol/l)
- Nephropathy (estimated glomerular filtration rate (eGFR) <60 ml/min and/or microalbuminuria with an albumin to creatinine ratio of 30-300 μg/mg)
- Known liver disease and/or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2 × normal values
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 |
|---|---|---|
| GlucagonAlso: Insulin, Somatostatin, 6,6 H2-glucosePancreatic clamp | Drug | Healthy Participants |
Primary outcome
Nadir of the total amino acid concentration during a two-hour high physiological glucagon infusion during a pancreatic clamp with somatostatin
Time frame: depending on the nadir between time 60 minutes and time 180 minutes
micromol/liter
3 secondary outcomes
average slope of the curve describing the change in the total amino acid concentration during 'supraphysiological' glucagon infusion
Time frame: between time 60 minutes and time 180 minutes
the incremental area under the curve (iAUC) for total amino acid concentrations during 'supraphysiological' glucagon infusion
Time frame: between time 60 minutes and time 180 minutes
the percentage change in amino acid concentration during the last hour of the 'supraphysiological' glucagon infusion as assessed by baseline subtracted AUC
Time frame: between time 60 minutes and time 180 minutes
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 11 May 2023.
- Derived from this study: PubMed 42866259Nagele NS, Suppli MP, Gilliam-Vigh H, Petersen N, Hartmann B, Knop FK, Lund AB, Jensen BAH. Short term overfeeding disrupts small intestinal barrier integrity and activates hepatic immunity in healthy men. iScience. 2026 Sep 22;29(10):117724. doi: 10.1016/j.isci.2026.117724. eCollection 2026 Oct 16.
- Derived from this study: PubMed 37967235Suppli MP, Hogedal A, Bagger JI, Chabanova E, van Hall G, Forman JL, Christensen MB, Albrechtsen NJW, Holst JJ, Knop FK. Signs of Glucagon Resistance After a 2-Week Hypercaloric Diet Intervention. J Clin Endocrinol Metab. 2024 Mar 15;109(4):955-967. doi: 10.1210/clinem/dgad666.
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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 in people with Non-Alcoholic Fatty Liver Disease and Glucagon Resistance, run by Malte Palm Suppli, MD 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 6 inclusion and 13 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 11 May 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?
Nadir of the total amino acid concentration during a two-hour high physiological glucagon infusion during a pancreatic clamp with somatostatin (time frame: depending on the nadir between time 60 minutes and time 180 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 NCT04859322, which also lists 2 linked publications.
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 11 May 2023.