NAFLD - Non-Alcoholic Fatty Liver DiseaseNCT04698486
Hepatic and Cardiac Metabolic Flexibility in Subjects With T2DM With and Without NAFLD
A study testing Hyperinsulinemic euglycaemic clamp in people with NAFLD - Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes, run by University of Aarhus at 1 site in Denmark.
Trial summary
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from simple reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH) and cirrhosis. Accumulating evidence indicates that NAFLD is associated with development of heart failure, abnormal ventricular glucose and fatty acid (FA)… Read more about this study
- Who is it for?
- Ages 30 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- NAFLD - Non-Alcoholic Fatty Liver Disease, Type 2 Diabetes
- What is being tested?
- Hyperinsulinemic euglycaemic clamp
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteDenmark
- Study dates
- 3 Jul 2020to 1 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 30 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects with Type 2 Diabetes with and without NAFLD (steatosis FF% > 5,6% on MR spectroscopy for NAFLD and NASH groups)
Who cannot join
- Active smoking
- Comorbidity other than hypertension and hyperlipidemia
- Fixed medical drug consumption (including insulin) except statins and anti-diabetic medications. However, statins and weekly based GLP-1 agonist must be paused 1 week before the examination date and other antidiabetic medication 3 days before the study date.
- Patients with cancer or former cancer patients
- Blood donation within the last 3 months prior to the study
- Participation in experiments involving radioactive isotopes within the last 3 months
- Alcohol abuse (over 21 items per week for men and over 14 for women)
- Pregnancy
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Endocrinology and Internal Medicine
Aarhus N, 8200
About this study
Official title: Investigation of Hepatic and Cardiac Fatty Acid Metabolism in Patients With Type 2 Diabetes Mellitus With and Without Non-alcoholic Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from simple reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH) and cirrhosis. Accumulating evidence indicates that NAFLD is associated with development of heart failure, abnormal ventricular glucose and fatty acid (FA) utilisation and cardiac steatosis. The mechanisms behind why some subjects progress from NAFLD to NASH and the link between cardiac involvement and NAFLD are poorly understood, but must include altered cardiac and intrahepatic lipid handling. Investigators plan comprehensive kinetic studies of heart and liver FA uptake and oxidation, ventricular function and substrate utilisation, and hepatic triglyceride (TG) secretion in order to assess mechanisms governing cardiac and hepatic lipid and glucose trafficking in subjects with type 2 diabetes with and without NAFLD and NASH and the relationship with heart function. In addition, the investigators will assess skeletal muscle and adipose tissue enzyme activities, gene expression and protein concentrations in type 2 diabetic subjects to define mechanisms involved in the cross-talk between heart, liver, muscle and adipose tissues. Investigators will address these questions using tracer techniques (11Cpalmitate PET tracers and triglyceride (TG) tracers) to study cardiac and liver substrate trafficking, as well as MR spectroscopy, echocardiography, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression. The overarching goals are to define abnormalities and differences between NAFLD and NASH in hepatic lipid (FA and TG) metabolism.
- Being tested
- Hyperinsulinemic euglycaemic clamp
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperinsulinemic euglycaemic clampOther
Infusion of constant intravenous insulin to achieve hyperinsulinemia and concomitant infusion of glucose to maintain euglycemia (plasma glucose at 5 mM).
Infusion of palmitate and VLDL-triglyceride tracer. PET/CT scans of heart and liver, both in basal period and during intervention.
| Study group | Role | What they receive |
|---|---|---|
| Type 2 Diabetes with NAFLD | Active comparator | Patients with Type 2 Diabetes with NAFLD
MR spectroscopy verified no steatosis Receives: Other: Hyperinsulinemic euglycaemic clamp |
| Type 2 Diabetes without NAFLD | Active comparator | Patients with Type 2 Diabetes without NAFLD
MR spectroscopy verified steatosis Receives: Other: Hyperinsulinemic euglycaemic clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatty acid uptake in Heart (mg/kg/min)
Infusion of [11-C] palmitate and measured by PET/CT scan.
Measured: 1 day
Fatty acid oxidation in Heart (µmol/min)
Infusion of [11-C] palmitate and measured by PET/CT scan.
Measured: 1 day
Secondary outcomes (6)
VLDL-triglyceride secretion (µmol/min)
Ex vivo labeled VLDL [14C]-triolein tracer technique.
Measured: 1 day
VLDL-triglyceride oxidation (µmol/min)
Oxidation is measured by specific activity in exhaled air.
Measured: 1 day
Fatty acid uptake in liver (mg/kg/min)
Infusion of [11-C] palmitate and measured by PET/CT scan.
Measured: 1 day
Fatty acid oxidation in liver (µmol/min)
Infusion of [11-C] palmitate and measured by PET/CT scan.
Measured: 1 day
VLDL-triglyceride uptake in muscle (percent)
Measurement of fatty acid concentration and specific activity in muscle biopsies
Measured: 1 day
VLDL-triglyceride uptake in adipose tissue (percent)
Measurement of fatty acid concentration and specific activity in adipose tissue biopsies
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2021
- Study start3 Jul 2020
- Primary completion1 Dec 2021
- Study completion1 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NAFLD - Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of AarhusThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Diabetes Academy
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04698486
- Sponsor's protocol ID
- 74772
- Status last verified
- Dec 2020
- First submitted
- 15 Dec 2020
- Last updated
- 27 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Hepatic and Cardiac Fatty Acid Metabolism in Patients With Type 2 Diabetes Mellitus With and Without Non-alcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT04698486
- Acronym / sponsor ID
- 74772
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Danish Diabetes Academy
- Study start
- 3 Jul 2020 (actual)
- Primary completion
- 1 Dec 2021 (actual)
- Study completion
- 1 Dec 2021 (actual)
- First posted
- 7 Jan 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.
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from simple reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH) and cirrhosis. Accumulating evidence indicates that NAFLD is associated with development of heart failure, abnormal ventricular glucose and fatty acid (FA) utilisation and cardiac steatosis. The mechanisms behind why some subjects progress from NAFLD to NASH and the link between cardiac involvement and NAFLD are poorly understood, but must include altered cardiac and intrahepatic lipid handling. Investigators plan comprehensive kinetic studies of heart and liver FA uptake and oxidation, ventricular function and substrate utilisation, and hepatic triglyceride (TG) secretion in order to assess mechanisms governing cardiac and hepatic lipid and glucose trafficking in subjects with type 2 diabetes with and without NAFLD and NASH and the relationship with heart function. In addition, the investigators will assess skeletal muscle and adipose tissue enzyme activities, gene expression and protein concentrations in type 2 diabetic subjects to define mechanisms involved in the cross-talk between heart, liver, muscle and adipose tissues. Investigators will address these questions using tracer techniques (11Cpalmitate PET tracers and triglyceride (TG) tracers) to study cardiac and liver substrate trafficking, as well as MR spectroscopy, echocardiography, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression. The overarching goals are to define abnormalities and differences between NAFLD and NASH in hepatic lipid (FA and TG) metabolism.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Type 2 Diabetes with NAFLD | Active comparator | Other: Hyperinsulinemic euglycaemic clampPatients with Type 2 Diabetes with NAFLD MR spectroscopy verified no steatosis |
| Type 2 Diabetes without NAFLD | Active comparator | Other: Hyperinsulinemic euglycaemic clampPatients with Type 2 Diabetes without NAFLD MR spectroscopy verified steatosis |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Subjects with Type 2 Diabetes with and without NAFLD (steatosis FF% > 5,6% on MR spectroscopy for NAFLD and NASH groups)
Key exclusion criteria (8 listed)
- Active smoking
- Comorbidity other than hypertension and hyperlipidemia
- Fixed medical drug consumption (including insulin) except statins and anti-diabetic medications. However, statins and weekly based GLP-1 agonist must be paused 1 week before the examination date and other antidiabetic medication 3 days before the study date.
- Patients with cancer or former cancer patients
- Blood donation within the last 3 months prior to the study
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 |
|---|---|---|
| Hyperinsulinemic euglycaemic clampInfusion of constant intravenous insulin to achieve hyperinsulinemia and concomitant infusion of glucose to maintain euglycemia (plasma glucose at 5 mM). Infusion of palmitate and VLDL-triglyceride tracer. PET/CT scans of heart and liver, both in basal period and during intervention. | Other | Type 2 Diabetes with NAFLD, Type 2 Diabetes without NAFLD |
Primary outcome
Fatty acid uptake in Heart (mg/kg/min)
Time frame: 1 day
Infusion of [11-C] palmitate and measured by PET/CT scan.
Fatty acid oxidation in Heart (µmol/min)
Time frame: 1 day
Infusion of [11-C] palmitate and measured by PET/CT scan.
6 secondary outcomes
VLDL-triglyceride secretion (µmol/min)
Time frame: 1 day
VLDL-triglyceride oxidation (µmol/min)
Time frame: 1 day
Fatty acid uptake in liver (mg/kg/min)
Time frame: 1 day
Fatty acid oxidation in liver (µmol/min)
Time frame: 1 day
VLDL-triglyceride uptake in muscle (percent)
Time frame: 1 day
VLDL-triglyceride uptake in adipose tissue (percent)
Time frame: 1 day
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 27 May 2022.
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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 Hyperinsulinemic euglycaemic clamp in people with NAFLD - Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes, 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 1 inclusion and 8 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 27 May 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?
Fatty acid uptake in Heart (mg/kg/min) (time frame: 1 day). 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?
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 27 May 2022.