Non-Alcoholic Fatty Liver DiseaseNCT04042142
Glucagon Resistance in Patients With NAFLD
A study testing glucagon in people with Non-Alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis, run by University of Aarhus at 1 site in Denmark.
Trial summary
The investigators propose that the sensitivity to glucagon in hepatic lipid metabolism is impaired in subjects with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). Read more about this study
- Who is it for?
- Ages 38 to 68 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, Glucose Metabolism Disorders
- 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
- 28 participants
- Where
- 1 siteDenmark
- Study dates
- 5 Oct 2019to 18 Aug 2022
- 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 38 to 68 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- BMI > 28 kg/m2
- steatosis FF% > 5,6% on MR spectroscopy for NAFLD and NASH groups
Who cannot join
- active smoking
- pregnancy
- comorbidity other than hypertension and hyperlipidemia
- participation in other radioactive isotope studies within the past 3-5 months (depending on radiation dose)
- blood donation (within 3 months)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: In-depth Studies of Glucagon Resistance on Hepatic Glucose, Fatty Acid and Triglyceride Kinetics and Generation of Toxic Lipid Intermediates in NAFLD and NASH.
The investigators propose that the sensitivity to glucagon in hepatic lipid metabolism is impaired in subjects with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). Moreover, they propose a dys-coordinated, reduced glucagon sensitivity in hepatic lipid metabolism and endogen glucose production in patients with NAFLD and NASH compared with healthy subjects and patients with simple steatosis. This reduced sensitivity may be the basis of a more severe dyslipidemia and the production of increased concentrations of toxic lipid intermediates in plasma and muscle tissue. The study will include healthy subjects with obesity and subjects with simple steatosis and NASH, tested at basal glucagonemia and moderate hyperglucagonemia to mimic insulin resistant levels during simultaneous somatostatin infusion and replacement doses of insulin and growth hormone. Infusion of palmitate, VLDL-triglyceride and glucose tracers in combination with indirect calorimetry as well as skeletal and adipose tissue biopsies will be employed to assess free fatty acid and VLDL-triglyceride kinetics (turnover, and oxidation) and hepatic fatty acid-esterification.
- Conditions
- Non-Alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, Glucose Metabolism Disorders
- Being tested
- glucagon
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Glucose Metabolism Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
glucagonOther
Infusion of low dose glucagon and high dose glucagon during simultaneous somatostatin infusion and replacement doses of insulin and growth hormone. Infusion of palmitate, VLDL-triglyceride and glucose tracers.
| Study group | Role | What they receive |
|---|---|---|
| Healthy overweight subjects | Active comparator | MR spectroscopy verified no steatosis Receives: Other: glucagon |
| Subjects with non-alcoholic fatty liver disease | Active comparator | MR spectroscopy verified steatosis, no steatohepatitis on liver biopsy Receives: Other: glucagon |
| Subjects with non-alcoholic steatohepatitis | Active comparator | MR spectroscopy verified steatosis, steatohepatitis on liver biopsy Receives: Other: glucagon |
What is being measured
The primary outcome is the main question the study is designed to answer.
VLDL-triglyceride kinetics (appearance rate (µmol/min) and oxidation (µmol/min))
Ex vivo labeled VLDL [14C]-triolein tracer technique. Oxidation is measured by specific activity in exhaled air.
Measured: 30 minutes at steady-state
Endogen glucose production (mmol/kg/min)
3-3H glucose tracer technique
Measured: 30 minutes at steady-state
Secondary outcomes (4)
LPL-activity (lipoprotein lipase, µmol/h)
Measured by the 'glycerol-stabilized substrate' method
Measured: 30 minutes at steady-state
VLDL-triglyceride-fatty acid uptake in muscle and fatty tissue (%)
Measurement of fatty acid concentration and specific activity in muscle- and adipose tissue biopsies
Measured: 30 minutes at steady-state
Expression of relevant genes in tissues
PCR in muscle- and adipose tissue biopsies
Measured: 30 minutes at steady-state
Fatty acid turnover (µmol/min)
Infusion af [9,10-3H] palmitate and measurement of specific activity in muscle and adipose tissue
Measured: 30 minutesat steady-state
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2019
- Study start5 Oct 2019
- Primary completion30 Jun 2022
- Study completion18 Aug 2022
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Council for Independent Research
- Responsible party
- Sponsor
- Investigators
- Sara Heebøll, Principal investigator, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04042142
- Sponsor's protocol ID
- 230279
- Status last verified
- Nov 2020
- First submitted
- 23 May 2019
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Heeboll S, Wegener G, Gronbaek H, Nielsen S. Comparable glucagon-stimulated amino acid suppression in individuals with and without hepatic steatosis or steatohepatitis. Am J Physiol Endocrinol Metab. 2024 Dec 1;327(6):E679-E685. doi: 10.1152/ajpendo.00187.2024. Epub 2024 Sep 18.
PubMed 39291967Heeboll S, Risikesan J, Ringgaard S, Kumarathas I, Sandahl TD, Gronbaek H, Sondergaard E, Nielsen S. Impaired Glucagon-Mediated Suppression of VLDL-Triglyceride Secretion in Individuals With Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD). Diabetes. 2022 Nov 1;71(11):2402-2411. doi: 10.2337/db22-0313.
PubMed 36001750
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In-depth Studies of Glucagon Resistance on Hepatic Glucose, Fatty Acid and Triglyceride Kinetics and Generation of Toxic Lipid Intermediates in NAFLD and NASH.
- ClinicalTrials.gov ID
- NCT04042142
- Acronym / sponsor ID
- 230279
- Conditions
- Non-Alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, Glucose Metabolism Disorders
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Danish Council for Independent Research
- Study start
- 5 Oct 2019 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 18 Aug 2022 (actual)
- First posted
- 1 Aug 2019 (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.
The investigators propose that the sensitivity to glucagon in hepatic lipid metabolism is impaired in subjects with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). Moreover, they propose a dys-coordinated, reduced glucagon sensitivity in hepatic lipid metabolism and endogen glucose production in patients with NAFLD and NASH compared with healthy subjects and patients with simple steatosis. This reduced sensitivity may be the basis of a more severe dyslipidemia and the production of increased concentrations of toxic lipid intermediates in plasma and muscle tissue. The study will include healthy subjects with obesity and subjects with simple steatosis and NASH, tested at basal glucagonemia and moderate hyperglucagonemia to mimic insulin resistant levels during simultaneous somatostatin infusion and replacement doses of insulin and growth hormone. Infusion of palmitate, VLDL-triglyceride and glucose tracers in combination with indirect calorimetry as well as skeletal and adipose tissue biopsies will be employed to assess free fatty acid and VLDL-triglyceride kinetics (turnover, and oxidation) and hepatic fatty acid-esterification.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy overweight subjects | Active comparator | Other: glucagonMR spectroscopy verified no steatosis |
| Subjects with non-alcoholic fatty liver disease | Active comparator | Other: glucagonMR spectroscopy verified steatosis, no steatohepatitis on liver biopsy |
| Subjects with non-alcoholic steatohepatitis | Active comparator | Other: glucagonMR spectroscopy verified steatosis, steatohepatitis on liver biopsy |
Who may qualify
- Ages
- 38 to 68 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- BMI > 28 kg/m2
- steatosis FF% > 5,6% on MR spectroscopy for NAFLD and NASH groups
Key exclusion criteria (5 listed)
- active smoking
- pregnancy
- comorbidity other than hypertension and hyperlipidemia
- participation in other radioactive isotope studies within the past 3-5 months (depending on radiation dose)
- blood donation (within 3 months)
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 |
|---|---|---|
| glucagonInfusion of low dose glucagon and high dose glucagon during simultaneous somatostatin infusion and replacement doses of insulin and growth hormone. Infusion of palmitate, VLDL-triglyceride and glucose tracers. | Other | Healthy overweight subjects, Subjects with non-alcoholic fatty liver disease, Subjects with non-alcoholic steatohepatitis |
Primary outcome
VLDL-triglyceride kinetics (appearance rate (µmol/min) and oxidation (µmol/min))
Time frame: 30 minutes at steady-state
Ex vivo labeled VLDL [14C]-triolein tracer technique. Oxidation is measured by specific activity in exhaled air.
Endogen glucose production (mmol/kg/min)
Time frame: 30 minutes at steady-state
3-3H glucose tracer technique
4 secondary outcomes
LPL-activity (lipoprotein lipase, µmol/h)
Time frame: 30 minutes at steady-state
VLDL-triglyceride-fatty acid uptake in muscle and fatty tissue (%)
Time frame: 30 minutes at steady-state
Expression of relevant genes in tissues
Time frame: 30 minutes at steady-state
Fatty acid turnover (µmol/min)
Time frame: 30 minutesat steady-state
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 4 Nov 2022.
- Derived from this study: PubMed 39291967Heeboll S, Wegener G, Gronbaek H, Nielsen S. Comparable glucagon-stimulated amino acid suppression in individuals with and without hepatic steatosis or steatohepatitis. Am J Physiol Endocrinol Metab. 2024 Dec 1;327(6):E679-E685. doi: 10.1152/ajpendo.00187.2024. Epub 2024 Sep 18.
- Derived from this study: PubMed 36001750Heeboll S, Risikesan J, Ringgaard S, Kumarathas I, Sandahl TD, Gronbaek H, Sondergaard E, Nielsen S. Impaired Glucagon-Mediated Suppression of VLDL-Triglyceride Secretion in Individuals With Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD). Diabetes. 2022 Nov 1;71(11):2402-2411. doi: 10.2337/db22-0313.
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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.
Sara Heebøll principal investigator
Aarhus University Hospital
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 Non-alcoholic Steatohepatitis, run by University of Aarhus 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 2 inclusion and 5 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 4 Nov 2022. 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?
VLDL-triglyceride kinetics (appearance rate (µmol/min) and oxidation (µmol/min)) (time frame: 30 minutes at steady-state). The study lists 2 primary outcomes in all. 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 NCT04042142, 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 4 Nov 2022.