Non-alcoholic Fatty Liver DiseaseNCT02075164
Unravelling Mechanisms of Fructose vs Glucose Consumption in the Pathogenesis and Progression of NAFLD
A study testing Fructose and Glucose in people with Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis, run by Prof. Michael Trauner, MD at 1 site in Austria.
Trial summary
Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum ranging from simple fatty liver over steatohepatitis (NASH) to liver cirrhosis and cancer (HCC) and is a major and increasing health problem affecting nearly 40% of the general population. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis
- What is being tested?
- Fructose and Glucose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteAustria
- Study dates
- May 2013to 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 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy men and women from 18 to 85, no disease history, no intake of regular medication, drugs, alcohol (alcohol consumption > 140 grams per week (or > 30g/day) 45) or herbals known to affect liver physiology, male and female (1:1), BMI <= 25.
- Patients with prior confirmed (biopsy within 6 months prior to study) intrahepatic fat accumulation/simple fatty liver (NAFL), HbA1c < 6.5, male and female (1:1)
- Patients with confirmed NASH (biopsy within 6 months prior to study), HbA1c < 6.5, male and female (1:1).
- Signed informed consent, willing and able to perform study procedures.
- General exclusion criteria (for all groups)
- Pregnancy and lactation (blood/urine pregnancy test will be performed for female volunteers at baseline and week 4)
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- Imprisoned persons
- Declined informed consent
- Inflammatory bowel conditions (celiac disease, Crohn's disease, ulcerative colitis)
- Prior bariatric surgery
- Alcoholic steatohepatitis and/or alcohol consumption > 140 grams per week (or > 30g/day) 45
- Other liver diseases (autoimmune, genetic, cholestatic, Wilson disease, Weber-Christian disease, partial lipodystrophy of the face sparing type, abetalipoproteinemia, and jejunal diverticulosis with bacterial overgrowth).
- Virus hepatitis (A, B, C)
- Known allergic reaction to the drugs used (see material and methods)
- Intake of drugs known to accumulate intrahepatic lipids and significantly interfere with metabolism (e.g. steroids/glucocorticoids, tamoxifen, amiodarone, perhexiline maleate, antiretroviral agents, tetracycline, minocycline, certain pesticides) 45
- Inability or contraindications to perform study procedures
- Fructose malabsorption diagnosed by two consecutive positive fructose hydrogen breath test
- MRI contraindications Study participants with claustrophobia Study participants carrying
- a cardiac pacemaker
- an insulin pump
- operation clips
- nerval stimulators
- implants or prostheses (e.g. ear implants, hip prostheses, heart valve, penile prosthesis)
- metal parts or metal fragments [e.g. metallic intrauterine devices (IUDs), marrow nail, metallic splinters or munition rests)
- metallic shunts or stents
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Medical University of Vienna, General Hospital of Vienna Vienna, Vienna, Austria 1090
Vienna, 1090
Michael Trauner, Prof. MD., 43140400 ext. 4741, michael.trauner@meduniwien.ac.at
Christian Kienbacher, MD, MSc
About this study
Official title: Unravelling the Pathogenetic Mechanisms of Fructose in Comparison to Glucose Consumption as Multiple Hit in the Pathogenesis and Progression of Non-alcoholic Fatty Liver Disease (NAFLD) - an Exploratory Trial
Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum ranging from simple fatty liver over steatohepatitis (NASH) to liver cirrhosis and cancer (HCC) and is a major and increasing health problem affecting nearly 40% of the general population. Moreover, NAFLD is an important risk factor for progression of diabetes and atherosclerosis. However, the pathomechanisms determining disease progression are poorly understood. The overall aim of this project is to test the central hypothesis that excessive fructose consumption provides a multiple metabolic hit in the pathogenesis and progression of NAFLD/NASH by impairment of hepatic lipid homeostasis and mitochondrial function resulting in hepatic lipotoxicity with inflammasome activation and disturbed interorgan cross-talk among insulin sensitive tissues.
Read the detailed description
To achieve these goals we will address the following specific hypotheses that
- Fructose-induced changes in lipid composition of hepatocellular stores determine lipotoxicity which may be associated with abnormalities in mitochondrial function, energy homeostasis, inflammasome activation and cellular injury in progression to NASH, effects which will be compared to glucose
- Non-invasive characterization of fructose (compared to glucose)-induced lipotoxic hepatic and extrahepatic metabolic risk profiles (lipid composition and energy metabolism) obtained by magnetic resonance spectroscopy (MRS) will identify patients with NASH
- Severity of fructose (compared to glucose)-induced lipotoxic lipid and adenosine triphosphate (ATP) derangements (identified by MRS) critically determines the degree of insulin resistance and abnormalities in hepatic glucose and lipid metabolism
- Compensatory hyperinsulinemia, secondary to skeletal muscle insulin resistance, may be a primary mechanism of hepatic lipotoxicity and progression to NASH
- Gender differences in the hepatic and systemic metabolic response to fructose are mediated by the impact of female sex hormones and their nuclear receptors on hepatic lipid metabolism, mitochondrial function and inflammasome activation.
- Age differences in the hepatic and systemic metabolic response to fructose are mediated by the impact of age related alterations on hepatic lipid metabolism and mitochondrial function.
These key hypotheses will be addressed by a translational research consortium including hepatologists, radiologists, physicists, endocrinologists and specialist in gender medicine allowing an integrated mechanistic approach to NAFLD. The strength of the current proposal comes directly from bridging basic science and clinical perspectives of different disciplines involved in the management of NAFLD, including cutting edge non-invasive technologies such as high field MRS metabolic profiling ('virtual metabolic liver biopsy') and mechanistic in vitro experiments. This project will provide novel mechanistic insights in the role of fructose as emerging hepatic 'toxin' in the pathogenesis and progression of NASH, as increasing health problem in Western society. Moreover, this study will clarify the impact of sex and gender on fructose-induced alterations in hepatic and systemic metabolism, providing a rational and scientific basis for future dietary interventions and regulatory actions.
- Being tested
- Fructose, Glucose
- Keywords
- Non-alcoholic Fatty Liver Disease, Non-alcoholic steatohepatitis, NAFLD, NASH
- 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.
FructoseDietary supplement
High oral Fructose challenge (150g per day for 56 days)
GlucoseDietary supplement
Dietary Supplement: High oral Fructose challenge (167g per day for 56 days)
| Study group | Role | What they receive |
|---|---|---|
| Fructose | Experimental | Volunteers will be challenged with oral 150g Fructose per day for 56 days. Receives: Dietary Supplement: Fructose; Dietary Supplement: Glucose |
| Glucose | Experimental | Volunteers will be challenged with oral 167g Fructose per day for 56 days. Receives: Dietary Supplement: Fructose; Dietary Supplement: Glucose |
| NAFLD | No intervention | Patients with confirmed simple fatty liver will be compared at baseline with other arms. |
| NASH | No intervention | Patients with confirmed non-alcoholic steatohepatitis will be compared at baseline with other arms. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intrahepatic total fat and ipid composition assessed by Magnetic resonance spectroscopy
At baseline and on the last day of the study (day 56) Magnetic resonance spectroscopy will be carried out in healthy volunteers. (Prior and after double-blinded fructose versus glucose consumption for 8 weeks in each healthy volunteer).
In NAFLD and NASH patients Magnetic resonance spectroscopy will only be carried out at baseline, as this arms/groups do not undergo an oral fructose/glucose challenge.
Baseline measures between healthy volunteers and NAFLD/NASH groups/arms will be compared to assess differences between healthy individuals and patients.
Baseline and day 56 measures in healthy volunteers after fructose/glucose consumption will be compared to assess the influence of the dietary challenge.
Measured: Healthy volunteers: Baseline, day 56 (8 weeks); NAFLD/NASH patients: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2014 (estimated)
- Study startMay 2013
- Primary completionJun 2021 (estimated)
- Study completionDec 2021 (estimated)
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.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prof. Michael Trauner, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Wiener Wissenschafts-, Forschungs- und Technologiefonds
- Responsible party
- Sponsor-investigator, Prof. Michael Trauner, MD, Medical University of Vienna
- Investigators
- Michael Trauner, Prof. MD, Principal investigator, Division of Gastroenterology and Hepatology Department of Internal Medicine III Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02075164
- Sponsor's protocol ID
- Fru2.0
- Status last verified
- Sep 2020
- First submitted
- 6 Feb 2014
- Last updated
- 7 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Smajis S, Gajdosik M, Pfleger L, Traussnigg S, Kienbacher C, Halilbasic E, Ranzenberger-Haider T, Stangl A, Beiglbock H, Wolf P, Lamp T, Hofer A, Gastaldelli A, Barbieri C, Luger A, Trattnig S, Kautzky-Willer A, Krssak M, Trauner M, Krebs M. Metabolic effects of a prolonged, very-high-dose dietary fructose challenge in healthy subjects. Am J Clin Nutr. 2020 Feb 1;111(2):369-377. doi: 10.1093/ajcn/nqz271.
PubMed 31796953
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unravelling the Pathogenetic Mechanisms of Fructose in Comparison to Glucose Consumption as Multiple Hit in the Pathogenesis and Progression of Non-alcoholic Fatty Liver Disease (NAFLD) - an Exploratory Trial
- ClinicalTrials.gov ID
- NCT02075164
- Acronym / sponsor ID
- Fru2.0
- Keywords
- Non-alcoholic Fatty Liver Disease, Non-alcoholic steatohepatitis, NAFLD, NASH
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Prof. Michael Trauner, MDUniversity, hospital or other
- Collaborators
- Wiener Wissenschafts-, Forschungs- und Technologiefonds
- Study start
- May 2013
- Primary completion
- Jun 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 3 Mar 2014 (estimated)
- 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) comprises a spectrum ranging from simple fatty liver over steatohepatitis (NASH) to liver cirrhosis and cancer (HCC) and is a major and increasing health problem affecting nearly 40% of the general population. Moreover, NAFLD is an important risk factor for progression of diabetes and atherosclerosis. However, the pathomechanisms determining disease progression are poorly understood. The overall aim of this project is to test the central hypothesis that excessive fructose consumption provides a multiple metabolic hit in the pathogenesis and progression of NAFLD/NASH by impairment of hepatic lipid homeostasis and mitochondrial function resulting in hepatic lipotoxicity with inflammasome activation and disturbed interorgan cross-talk among insulin sensitive tissues.
Detailed description
To achieve these goals we will address the following specific hypotheses that
- Fructose-induced changes in lipid composition of hepatocellular stores determine lipotoxicity which may be associated with abnormalities in mitochondrial function, energy homeostasis, inflammasome activation and cellular injury in progression to NASH, effects which will be compared to glucose
- Non-invasive characterization of fructose (compared to glucose)-induced lipotoxic hepatic and extrahepatic metabolic risk profiles (lipid composition and energy metabolism) obtained by magnetic resonance spectroscopy (MRS) will identify patients with NASH
- Severity of fructose (compared to glucose)-induced lipotoxic lipid and adenosine triphosphate (ATP) derangements (identified by MRS) critically determines the degree of insulin resistance and abnormalities in hepatic glucose and lipid metabolism
- Compensatory hyperinsulinemia, secondary to skeletal muscle insulin resistance, may be a primary mechanism of hepatic lipotoxicity and progression to NASH
- Gender differences in the hepatic and systemic metabolic response to fructose are mediated by the impact of female sex hormones and their nuclear receptors on hepatic lipid metabolism, mitochondrial function and inflammasome activation.
- Age differences in the hepatic and systemic metabolic response to fructose are mediated by the impact of age related alterations on hepatic lipid metabolism and mitochondrial function.
These key hypotheses will be addressed by a translational research consortium including hepatologists, radiologists, physicists, endocrinologists and specialist in gender medicine allowing an integrated mechanistic approach to NAFLD. The strength of the current proposal comes directly from bridging basic science and clinical perspectives of different disciplines involved in the management of NAFLD, including cutting edge non-invasive technologies such as high field MRS metabolic profiling ('virtual metabolic liver biopsy') and mechanistic in vitro experiments. This project will provide novel mechanistic insights in the role of fructose as emerging hepatic 'toxin' in the pathogenesis and progression of NASH, as increasing health problem in Western society. Moreover, this study will clarify the impact of sex and gender on fructose-induced alterations in hepatic and systemic metabolism, providing a rational and scientific basis for future dietary interventions and regulatory actions.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Fructose | Experimental | Dietary Supplement: Fructose, Dietary Supplement: GlucoseVolunteers will be challenged with oral 150g Fructose per day for 56 days. |
| Glucose | Experimental | Dietary Supplement: Fructose, Dietary Supplement: GlucoseVolunteers will be challenged with oral 167g Fructose per day for 56 days. |
| NAFLD | No intervention | –Patients with confirmed simple fatty liver will be compared at baseline with other arms. |
| NASH | No intervention | –Patients with confirmed non-alcoholic steatohepatitis will be compared at baseline with other arms. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Healthy men and women from 18 to 85, no disease history, no intake of regular medication, drugs, alcohol (alcohol consumption > 140 grams per week (or > 30g/day) 45) or herbals known to affect liver physiology, male and female (1:1), BMI <= 25.
- Patients with prior confirmed (biopsy within 6 months prior to study) intrahepatic fat accumulation/simple fatty liver (NAFL), HbA1c < 6.5, male and female (1:1)
- Patients with confirmed NASH (biopsy within 6 months prior to study), HbA1c < 6.5, male and female (1:1).
- Signed informed consent, willing and able to perform study procedures.
- General exclusion criteria (for all groups)
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| FructoseHigh oral Fructose challenge (150g per day for 56 days) | Dietary supplement | Fructose, Glucose |
| GlucoseDietary Supplement: High oral Fructose challenge (167g per day for 56 days) | Dietary supplement | Fructose, Glucose |
Primary outcome
Intrahepatic total fat and ipid composition assessed by Magnetic resonance spectroscopy
Time frame: Healthy volunteers: Baseline, day 56 (8 weeks); NAFLD/NASH patients: Baseline
At baseline and on the last day of the study (day 56) Magnetic resonance spectroscopy will be carried out in healthy volunteers. (Prior and after double-blinded fructose versus glucose consumption for 8 weeks in each healthy volunteer). In NAFLD and NASH patients Magnetic resonance spectroscopy will only be carried out at baseline, as this arms/groups do not undergo an oral fructose/glucose challenge. Baseline measures between healthy volunteers and NAFLD/NASH groups/arms will be compared to assess differences between healthy individuals and patients. Baseline and day 56 measures in healthy volunteers after fructose/glucose consumption will be compared to assess the influence of the dietary challenge.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2020.
- Derived from this study: PubMed 31796953Smajis S, Gajdosik M, Pfleger L, Traussnigg S, Kienbacher C, Halilbasic E, Ranzenberger-Haider T, Stangl A, Beiglbock H, Wolf P, Lamp T, Hofer A, Gastaldelli A, Barbieri C, Luger A, Trattnig S, Kautzky-Willer A, Krssak M, Trauner M, Krebs M. Metabolic effects of a prolonged, very-high-dose dietary fructose challenge in healthy subjects. Am J Clin Nutr. 2020 Feb 1;111(2):369-377. doi: 10.1093/ajcn/nqz271.
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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.
Michael Trauner, Prof. MD principal investigator
Division of Gastroenterology and Hepatology Department of Internal Medicine III Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fructose and Glucose in people with Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis, run by Prof. Michael Trauner, MD at 1 site in Austria.
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 25 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 7 Sep 2020. 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 Austria. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michael Trauner, Prof. MD. (+43140400 ext. 4741, michael.trauner@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intrahepatic total fat and ipid composition assessed by Magnetic resonance spectroscopy (time frame: Healthy volunteers: Baseline, day 56 (8 weeks); NAFLD/NASH patients: Baseline). 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 NCT02075164, 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 7 Sep 2020.