NAFLDNCT05044130
Postprandial VLDL-triglyceride Metabolism in Type 2 Diabetes Patients With and Without NAFLD
A study testing High-fat mixed-meal tolerance test (HF-MMTT) in people with NAFLD 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). The mechanisms behind why some subjects progress from NAFLD to NASH are not clear and the responsible mechanism for storage of excess amounts of liver fat in… Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- NAFLD, Type 2 Diabetes
- What is being tested?
- High-fat mixed-meal tolerance test (HF-MMTT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteDenmark
- Study dates
- 14 Sep 2021to 23 Apr 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 30 to 70 years
- All sexes
- No healthy volunteers
- 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 must be paused 2 weeks before the examination date and other antidiabetic medication on examination 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: Postprandial Hepatic Fatty Acid Metabolism During Oral High-fat Mixed-meal Challenge Test in Patients With Type 2 Diabetes With and Without NAFLD
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from simple reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH). The mechanisms behind why some subjects progress from NAFLD to NASH are not clear and the responsible mechanism for storage of excess amounts of liver fat in patients with NAFLD are poorly understood.
Patients with type 2 diabetes mellitus (T2D) and abdominally obese subjects very often have accumulation of liver fat (NAFLD).
Read more
T2D is also associated with abnormal lipid metabolism (dyslipidemia), including free fatty acids (FFA), hypertriglyceridemia and excessive postprandial hyperlipidemia which increases the risk of ischemic cardiovascular disease (CVD) and heart failure.
In healthy, insulin sensitive subjects the postprandial increase in triglycerides (TG) is primarily caused by meal derived chylomicrons, whereas endogenously produced TG (VLDL-TG) and decreased peripheral TG clearance only becomes quantitatively important in insulin resistant subjects .Thus, postprandial lipidemia in T2D results from both chylomicronemia as well as a reduction in both insulin mediated suppression of VLDL-TG secretion and lipoprotein lipase (LPL) mediated peripheral clearance. A recent study demonstrated that the ability of insulin to suppress hepatic VLDL-TG after a fat-enriched meal and the duration of the postprandial hyperlipidemia was similar in patients with T2D compared with age- and BMI matched individuals without T2D, indicating that the degree of insulin mediated VLDL-TG secretion and hyperlipidemia primarily depends on insulin sensitivity and not the presence of T2D diabetes per se.
In these studies, the investigators want to examine the effect of a fat enriched mixed-meal on hepatic VLDL-TG handling and adipose storage capacity in patients with T2D with and without NAFLD. Investigators will address these questions using carboxyl-14C triolein labeled VLDL-TG, magnetic resonance (MR) spectroscopy of liver, 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 patients with T2D with and without NAFLD in terms of hepatic lipid metabolism.
- Conditions
- NAFLD, Type 2 Diabetes
- Being tested
- High-fat mixed-meal tolerance test (HF-MMTT)
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-fat mixed-meal tolerance test (HF-MMTT)Dietary supplement
The test meal consists of a standardized HF-MMTT (791 cal) with 197 g cream (38 % fat), 18 g sugar and 1 g vanilla sugar for taste (75 g fat, 25 g carbohydrate and 4 g protein)
| Study group | Role | What they receive |
|---|---|---|
| Type 2 Diabetes with NAFLD | Active comparator | Patients with Type 2 Diabetes with NAFLD
MR spectroscopy verified steatosis Receives: Dietary Supplement: High-fat mixed-meal tolerance test (HF-MMTT) |
| Type 2 Diabetes without NAFLD | Active comparator | Patients with Type 2 Diabetes without NAFLD
MR spectroscopy verified no steatosis Receives: Dietary Supplement: High-fat mixed-meal tolerance test (HF-MMTT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
VLDL-triglyceride secretion - Ex vivo labeled VLDL - [14C]-triolein tracer technique.
(μmol/min)
Measured: 1 day
VLDL-triglyceride uptake in muscle - Measurement of fatty acid concentration and specific activity in muscle biopsies
(percent)
Measured: 1 day
VLDL-triglyceride uptake in adipose tissue - Measurement of fatty acid concentration and specific activity in adipose tissue biopsies
(percent)
Measured: 1 day
Secondary outcomes (3)
VLDL-triglyceride oxidation - Oxidation is measured by specific activity in exhaled air.
(μmol/min)
Measured: 1 day
Adipose cell size measurement
(μl)
Measured: 1 day
Insulin sensitivity
(mg/kg/min)
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 posted14 Sep 2021
- Study start14 Sep 2021
- Primary completion23 Feb 2023
- Study completion23 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NAFLDStudies 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
- NCT05044130
- Sponsor's protocol ID
- 01072021
- Status last verified
- Mar 2024
- First submitted
- 4 Sep 2021
- Last updated
- 21 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Postprandial Hepatic Fatty Acid Metabolism During Oral High-fat Mixed-meal Challenge Test in Patients With Type 2 Diabetes With and Without NAFLD
- ClinicalTrials.gov ID
- NCT05044130
- Acronym / sponsor ID
- 01072021
- Conditions
- NAFLD, Type 2 Diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Danish Diabetes Academy
- Study start
- 14 Sep 2021 (actual)
- Primary completion
- 23 Feb 2023 (actual)
- Study completion
- 23 Apr 2023 (actual)
- First posted
- 14 Sep 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). The mechanisms behind why some subjects progress from NAFLD to NASH are not clear and the responsible mechanism for storage of excess amounts of liver fat in patients with NAFLD are poorly understood.
Patients with type 2 diabetes mellitus (T2D) and abdominally obese subjects very often have accumulation of liver fat (NAFLD).
T2D is also associated with abnormal lipid metabolism (dyslipidemia), including free fatty acids (FFA), hypertriglyceridemia and excessive postprandial hyperlipidemia which increases the risk of ischemic cardiovascular disease (CVD) and heart failure.
In healthy, insulin sensitive subjects the postprandial increase in triglycerides (TG) is primarily caused by meal derived chylomicrons, whereas endogenously produced TG (VLDL-TG) and decreased peripheral TG clearance only becomes quantitatively important in insulin resistant subjects .Thus, postprandial lipidemia in T2D results from both chylomicronemia as well as a reduction in both insulin mediated suppression of VLDL-TG secretion and lipoprotein lipase (LPL) mediated peripheral clearance. A recent study demonstrated that the ability of insulin to suppress hepatic VLDL-TG after a fat-enriched meal and the duration of the postprandial hyperlipidemia was similar in patients with T2D compared with age- and BMI matched individuals without T2D, indicating that the degree of insulin mediated VLDL-TG secretion and hyperlipidemia primarily depends on insulin sensitivity and not the presence of T2D diabetes per se.
In these studies, the investigators want to examine the effect of a fat enriched mixed-meal on hepatic VLDL-TG handling and adipose storage capacity in patients with T2D with and without NAFLD. Investigators will address these questions using carboxyl-14C triolein labeled VLDL-TG, magnetic resonance (MR) spectroscopy of liver, 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 patients with T2D with and without NAFLD in terms of hepatic lipid 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 | Dietary Supplement: High-fat mixed-meal tolerance test (HF-MMTT)Patients with Type 2 Diabetes with NAFLD MR spectroscopy verified steatosis |
| Type 2 Diabetes without NAFLD | Active comparator | Dietary Supplement: High-fat mixed-meal tolerance test (HF-MMTT)Patients with Type 2 Diabetes without NAFLD MR spectroscopy verified no steatosis |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not 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 must be paused 2 weeks before the examination date and other antidiabetic medication on examination 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 |
|---|---|---|
| High-fat mixed-meal tolerance test (HF-MMTT)The test meal consists of a standardized HF-MMTT (791 cal) with 197 g cream (38 % fat), 18 g sugar and 1 g vanilla sugar for taste (75 g fat, 25 g carbohydrate and 4 g protein) | Dietary supplement | Type 2 Diabetes with NAFLD, Type 2 Diabetes without NAFLD |
Primary outcome
VLDL-triglyceride secretion - Ex vivo labeled VLDL - [14C]-triolein tracer technique.
Time frame: 1 day
(μmol/min)
VLDL-triglyceride uptake in muscle - Measurement of fatty acid concentration and specific activity in muscle biopsies
Time frame: 1 day
(percent)
VLDL-triglyceride uptake in adipose tissue - Measurement of fatty acid concentration and specific activity in adipose tissue biopsies
Time frame: 1 day
(percent)
3 secondary outcomes
VLDL-triglyceride oxidation - Oxidation is measured by specific activity in exhaled air.
Time frame: 1 day
Adipose cell size measurement
Time frame: 1 day
Insulin sensitivity
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 21 Mar 2024.
Related trials for NAFLD
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
Active, not recruiting
Target of Suv420h1/2 in Hepatocytes
NAFLD
Active, not recruitingObservational study
Non-Invasive MASLD Diagnosis & T2D Remission Biomarkers
MASLD, T2DM (Type 2 Diabetes Mellitus)
Not yet recruitingPhase 2/3
Evaluating the Safety and Efficacy of Roflumilast in the Treatment of Nonalcoholic Fatty Liver Disease Patients
NAFLD (Nonalcoholic Fatty Liver Disease)
Not yet recruitingPhase 2/3
Evaluating the Safety and Efficacy of Rupatadine in the Treatment of Nonalcoholic Fatty Liver Disease Patients.
NAFLD (Nonalcoholic Fatty Liver Disease)
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 High-fat mixed-meal tolerance test (HF-MMTT) in people with NAFLD 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 21 Mar 2024. 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 secretion - Ex vivo labeled VLDL - [14C]-triolein tracer technique. (time frame: 1 day). The study lists 3 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 21 Mar 2024.