Exercise TherapyCENSORIALNCT06359444
Effect of High Intensity Exercise Rehabilitation on Liver Function and Insulin Sensitivity in Patients With MASLD
A study testing Combined aerobic + strength training and Combined strength + HIIT training in people with Exercise Therapy and Metabolic Dysfunction-associated Steatotic Liver Disease, run by University Ghent at 1 site in Belgium.
Trial summary
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, and is associated with obesity and the metabolic syndrome. Physical activity and lifestyle interventions are among the most recommended treatments for individuals with MASLD. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Exercise Therapy, Metabolic Dysfunction-associated Steatotic Liver Disease
- What is being tested?
- Combined aerobic + strength training and Combined strength + HIIT training
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 1 siteBelgium
- Study dates
- 26 Apr 2024to 15 Mar 2026
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with MASLD by ultrasound, CAP and/or biopsy
- Age between 18 and 75 years old
- No significant liver fibrosis (Fibroscan < 7.5 kPa; if it is between >7.5 and <10, there must be absence of liver fibrosis in the biopsy)
Who cannot join
- Presence of other liver diseases that may contribute to the clinical presentation in the patient
- Severe cardiovascular, orthopedic, physical or other illnesses that make it impossible to participate in the study's exercise rehabilitation program or where safety cannot be guaranteed
- Pregnancy
- Pharmacological treatment that directly affects MASLD (e.g. GLP-1 analogues)
- A change in medication in the last three months before the study that affects metabolic disease stability
Trial locations and contacts
1 site in 1 country.
Sander Lefere, dr. contact
Belgium1 site, 1 recruiting
- Recruiting
Ghent University Hospital
Ghent, 9000
Anja Geerts, MD, PhD
About this study
Official title: Effect of High Intensity Exercise Rehabilitation on Hepatic Fatty Acids (Liver Function), Insulin Sensitivity and Cardiovascular Risk in Patients With MASLD
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, and is associated with obesity and the metabolic syndrome. Physical activity and lifestyle interventions are among the most recommended treatments for individuals with MASLD.
In this RCT, we will evaluate the effect of combined exercise training "strength and aerobic training" versus "strength and high intensity training (HIIT)". The main outcome parameter is the severity of liver steatosis. Patients will be recruited at the fatty liver clinic of the UZ Gent.
Read the detailed description
Physical activity and lifestyle interventions, including exercise, are recommended for individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). Weight loss has been found to improve MASLD histologically, but exercise alone can also reduce liver fat accumulation, even without significant weight loss. Exercise has positive effects on chronic inflammation, type 2 diabetes mellitus (T2DM), and mitochondrial function in MASLD patients. Studies suggest that both aerobic and resistance exercise are effective in reducing fat content and liver enzyme levels in MASLD, and thereby generate positive effects on insulin sensitivity and cardiovascular risk. The potential of high-intensity interval training (HIIT) is large in various settings, but was never explored in this population. Moreover, the combination with strength training can have additional health effects which remain to be explored.
All subjects are recruited in the liver steatosis outpatient clinic of the university hospital in Ghent by the physicians and researchers of this study. After patient selection and obtaining informed consent, they will be screened in the rehabilitation center for cardiorespiratory fitness.
- Being tested
- Combined aerobic + strength training, Combined strength + HIIT training
- Keywords
- exercise, MASLD, liver diseases
- Medical subject headings
- Motor Activity, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combined aerobic + strength trainingOther
Participants will follow a combination of endurance and strength training for 14 weeks.
There will be three sessions every week: two at Ghent university department of rehabilitation and one at home. Each session will last approximately one hour.
Combined strength + HIIT trainingOther
6 weeks of endurance training and strength training, 8 weeks of strength training and HIIT.
Participants will follow the same combination of endurance and strength training for the first six weeks, to build up to a baseline level of physical fitness. They will then switch to eight weeks of a combination of strength training and High Intensity Interval Training (HIIT).
There will be three sessions every week: two at Ghent university department of rehabilitation and one at home. Each session will last approximately one hour.
| Study group | Role | What they receive |
|---|---|---|
| Combined strength + aerobic training | Active comparator | The patients in this group will exercise for 14 weeks. It is a combination of strength and aerobic exercise. Receives: Other: Combined aerobic + strength training |
| Combined strength + HIIT | Experimental | The patients in this group will exercise for 14 weeks. The first 6 weeks consists of combined aerobic and strength exercise, following the protocol from the active comparator group.
They will switch to combined strength and HIIT exercise for the remaining 8 weeks. Receives: Other: Combined strength + HIIT training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver steatosis by CAP
Liver stiffness measurement will be performed using vibration-controlled transient elastography, more specifically the Fibroscan. This method measures the fat accumulation in the liver (dB/m) and the level of scar tissue (kPa), represented as the CAP or steatosis score and the fibrosis score respectively.
Measured: before training and after training (14 weeks)
Liver steatosis on ultrasound
Ultrasound can demonstrate hepatic fatty tissue, estimating severity based on liver-kidney contrast, resolution loss thv the intrahepatic blood vessels, and visibility of the diaphragm. On this basis, a score 0-3 can be assigned.
Measured: before training and after training (14 weeks)
Secondary outcomes (16)
Insulin sensitivity
Insulin sensitivity will be assessed by calculation of the HOMA-IR index (fasting glucose x insulin)
Measured: before training and after training (14 weeks)
Liver transaminases
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes located primarily in liver cells. An elevation of these enzymes in the bloodstream may indicate liver damage or inflammation.
Measured: before training and after training (14 weeks)
Maximal exercise test
A ramp protocol will be performed starting at 25 watts, adding 25 watts per minute each time.
This test will be administered using ergospirometry to derive measures for aerobic physical condition.
Measured: before training and after training (14 weeks)
Strength
Strength will be measured by 1RM determination of the muscle groups that will be trained (leg press, adductors, vertical traction, chest press, abdominal and back muscles). This measurement will be performed at baseline, after 10 weeks and at the end of the study
Measured: before training and after training (14 weeks)
Cardiovascular function
Blood pressure measurements:
Before and after exercise, systole and diastole blood pressure will be measured. Blood pressure will be measured three times and the average value recorded.
Measured: before training and after training (14 weeks)
Weight
Weight will be measured using a scale to the nearest 0.1 kilogram (kg).
Measured: before training and after training (14 weeks)
Heigth
Height will be measured to the nearest 0.1 meter (m) with a stadiometer.
Measured: before training and after training (14 weeks)
BMI
BMI will be calculated.
Measured: before training and after training (14 weeks)
waist
Waist circumference is measured in standing position with a measuring tape just above the iliac crest, to the nearest 0.1 centimeter (cm).
Measured: before training and after training (14 weeks)
BIA
Bioelectrical impedance analysis (BIA) will be performed to determine lean mass and fat percentage.
Measured: before training and after training (14 weeks)
Interleukine
IL-6 and IL-8 serum levels will be measured in blood. These are correlate with the progression of liver fibrosis and are elevated in patients with chronic liver disease.
Measured: before training and after training (14 weeks)
TNF-alfa
TNF-α is a pro-inflammatory cytokine produced by macrophages and will be measured in blood. Inflammation in NAFLD causes TNF-α to be released into the body. The amount is increased in patients with NAFLD and correlates with the level of fat mass and insulin resistance.
Measured: before training and after training (14 weeks)
Hepatokines
Hepatokines will be measured in blood. These are proteins secreted by the liver which have a demonstrated association with metabolic function/dysfunction. These include fetuin-A, FGF-21, follistatin etc.
Measured: before training and after training (14 weeks)
Myokines
Myokines will be measured in blood. These are proteins secreted by the muscle which have a demonstrated association with metabolic function/dysfunction. These include myostatin, brain-derived neurotrophic factor, etc....
Measured: before training and after training (14 weeks)
Adipokines
Adipokines will be measured in blood. These are proteins secreted by the adipose tissue which have a demonstrated association with metabolic function/dysfunction. These include leptin, adiponectin, etc.
Measured: before training and after training (14 weeks)
SF-36
Quality of life will be measured using SF-36 (a standard questionnaire).
Measured: before training and after training (14 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2024
- Study start26 Apr 2024
- Primary completion15 Mar 2026 (estimated)
- Study completion15 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Exercise TherapyStudies of the same condition, open and under way.
- More trials run by University GhentThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized in two groups: (a) combined aerobic and strength and (b) combined high intensity and strength.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Ghent
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Ghent
- Responsible party
- Sponsor
- Investigators
- Patrick Calders, Prof. dr., Principal investigator, University GhentAnja Geerts, Prof. dr., Principal investigator, University Hospital, GhentSander Lefere, dr., Study chair, University Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06359444
- Sponsor's protocol ID
- ONZ-2023-0453
- Acronym
- CENSORIAL
- Status last verified
- Jun 2024
- First submitted
- 1 Feb 2024
- Last updated
- 7 Jun 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012 Jul;57(1):157-66. doi: 10.1016/j.jhep.2012.02.023. Epub 2012 Mar 10.
PubMed 22414768Hashida R, Kawaguchi T, Bekki M, Omoto M, Matsuse H, Nago T, Takano Y, Ueno T, Koga H, George J, Shiba N, Torimura T. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: A systematic review. J Hepatol. 2017 Jan;66(1):142-152. doi: 10.1016/j.jhep.2016.08.023. Epub 2016 Sep 14.
PubMed 27639843Oh S, Tsujimoto T, Kim B, Uchida F, Suzuki H, Iizumi S, Isobe T, Sakae T, Tanaka K, Shoda J. Weight-loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD. JHEP Rep. 2021 Feb 10;3(3):100253. doi: 10.1016/j.jhepr.2021.100253. eCollection 2021 Jun.
PubMed 33898958Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Ledinghen V, Kumar M, Lupsor-Platon M, Han KH, Cardoso AC, Ferraioli G, Chan WK, Wong VW, Myers RP, Chayama K, Friedrich-Rust M, Beaugrand M, Shen F, Hiriart JB, Sarin SK, Badea R, Jung KS, Marcellin P, Filice C, Mahadeva S, Wong GL, Crotty P, Masaki K, Bojunga J, Bedossa P, Keim V, Wiegand J. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol. 2017 May;66(5):1022-1030. doi: 10.1016/j.jhep.2016.12.022. Epub 2016 Dec 28.
PubMed 28039099
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of High Intensity Exercise Rehabilitation on Hepatic Fatty Acids (Liver Function), Insulin Sensitivity and Cardiovascular Risk in Patients With MASLD
- ClinicalTrials.gov ID
- NCT06359444
- Acronym / sponsor ID
- CENSORIAL / ONZ-2023-0453
- Keywords
- exercise, MASLD, liver diseases
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- University GhentUniversity, hospital or other
- Collaborators
- University Hospital, Ghent
- Study start
- 26 Apr 2024 (actual)
- Primary completion
- 15 Mar 2026 (estimated)
- Study completion
- 15 Mar 2026 (estimated)
- First posted
- 11 Apr 2024 (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.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, and is associated with obesity and the metabolic syndrome. Physical activity and lifestyle interventions are among the most recommended treatments for individuals with MASLD.
In this RCT, we will evaluate the effect of combined exercise training "strength and aerobic training" versus "strength and high intensity training (HIIT)". The main outcome parameter is the severity of liver steatosis. Patients will be recruited at the fatty liver clinic of the UZ Gent.
Detailed description
Physical activity and lifestyle interventions, including exercise, are recommended for individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). Weight loss has been found to improve MASLD histologically, but exercise alone can also reduce liver fat accumulation, even without significant weight loss. Exercise has positive effects on chronic inflammation, type 2 diabetes mellitus (T2DM), and mitochondrial function in MASLD patients. Studies suggest that both aerobic and resistance exercise are effective in reducing fat content and liver enzyme levels in MASLD, and thereby generate positive effects on insulin sensitivity and cardiovascular risk. The potential of high-intensity interval training (HIIT) is large in various settings, but was never explored in this population. Moreover, the combination with strength training can have additional health effects which remain to be explored.
All subjects are recruited in the liver steatosis outpatient clinic of the university hospital in Ghent by the physicians and researchers of this study. After patient selection and obtaining informed consent, they will be screened in the rehabilitation center for cardiorespiratory fitness.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will be randomized in two groups: (a) combined aerobic and strength and (b) combined high intensity and strength.
| Arm | Type | Receives |
|---|---|---|
| Combined strength + aerobic training | Active comparator | Other: Combined aerobic + strength trainingThe patients in this group will exercise for 14 weeks. It is a combination of strength and aerobic exercise. |
| Combined strength + HIIT | Experimental | Other: Combined strength + HIIT trainingThe patients in this group will exercise for 14 weeks. The first 6 weeks consists of combined aerobic and strength exercise, following the protocol from the active comparator group. They will switch to combined strength and HIIT exercise for the remaining 8 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosed with MASLD by ultrasound, CAP and/or biopsy
- Age between 18 and 75 years old
- No significant liver fibrosis (Fibroscan < 7.5 kPa; if it is between >7.5 and <10, there must be absence of liver fibrosis in the biopsy)
Key exclusion criteria (5 listed)
- Presence of other liver diseases that may contribute to the clinical presentation in the patient
- Severe cardiovascular, orthopedic, physical or other illnesses that make it impossible to participate in the study's exercise rehabilitation program or where safety cannot be guaranteed
- Pregnancy
- Pharmacological treatment that directly affects MASLD (e.g. GLP-1 analogues)
- A change in medication in the last three months before the study that affects metabolic disease stability
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 |
|---|---|---|
| Combined aerobic + strength trainingParticipants will follow a combination of endurance and strength training for 14 weeks. There will be three sessions every week: two at Ghent university department of rehabilitation and one at home. Each session will last approximately one hour. | Other | Combined strength + aerobic training |
| Combined strength + HIIT training6 weeks of endurance training and strength training, 8 weeks of strength training and HIIT. Participants will follow the same combination of endurance and strength training for the first six weeks, to build up to a baseline level of physical fitness. They will then switch to eight weeks of a combination of strength training and High Intensity Interval Training (HIIT). There will be three sessions every week: two at Ghent university department of rehabilitation and one at home. Each session will last approximately one hour. | Other | Combined strength + HIIT |
Primary outcome
Liver steatosis by CAP
Time frame: before training and after training (14 weeks)
Liver stiffness measurement will be performed using vibration-controlled transient elastography, more specifically the Fibroscan. This method measures the fat accumulation in the liver (dB/m) and the level of scar tissue (kPa), represented as the CAP or steatosis score and the fibrosis score respectively.
Liver steatosis on ultrasound
Time frame: before training and after training (14 weeks)
Ultrasound can demonstrate hepatic fatty tissue, estimating severity based on liver-kidney contrast, resolution loss thv the intrahepatic blood vessels, and visibility of the diaphragm. On this basis, a score 0-3 can be assigned.
16 secondary outcomes
Insulin sensitivity
Time frame: before training and after training (14 weeks)
Liver transaminases
Time frame: before training and after training (14 weeks)
Maximal exercise test
Time frame: before training and after training (14 weeks)
Strength
Time frame: before training and after training (14 weeks)
Cardiovascular function
Time frame: before training and after training (14 weeks)
Weight
Time frame: before training and after training (14 weeks)
Heigth
Time frame: before training and after training (14 weeks)
BMI
Time frame: before training and after training (14 weeks)
waist
Time frame: before training and after training (14 weeks)
BIA
Time frame: before training and after training (14 weeks)
Interleukine
Time frame: before training and after training (14 weeks)
TNF-alfa
Time frame: before training and after training (14 weeks)
Hepatokines
Time frame: before training and after training (14 weeks)
Myokines
Time frame: before training and after training (14 weeks)
Adipokines
Time frame: before training and after training (14 weeks)
SF-36
Time frame: before training and after training (14 weeks)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2024.
- Background: PubMed 22414768Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012 Jul;57(1):157-66. doi: 10.1016/j.jhep.2012.02.023. Epub 2012 Mar 10.
- Background: PubMed 27639843Hashida R, Kawaguchi T, Bekki M, Omoto M, Matsuse H, Nago T, Takano Y, Ueno T, Koga H, George J, Shiba N, Torimura T. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: A systematic review. J Hepatol. 2017 Jan;66(1):142-152. doi: 10.1016/j.jhep.2016.08.023. Epub 2016 Sep 14.
- Background: PubMed 33898958Oh S, Tsujimoto T, Kim B, Uchida F, Suzuki H, Iizumi S, Isobe T, Sakae T, Tanaka K, Shoda J. Weight-loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD. JHEP Rep. 2021 Feb 10;3(3):100253. doi: 10.1016/j.jhepr.2021.100253. eCollection 2021 Jun.
- Background: PubMed 28039099Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Ledinghen V, Kumar M, Lupsor-Platon M, Han KH, Cardoso AC, Ferraioli G, Chan WK, Wong VW, Myers RP, Chayama K, Friedrich-Rust M, Beaugrand M, Shen F, Hiriart JB, Sarin SK, Badea R, Jung KS, Marcellin P, Filice C, Mahadeva S, Wong GL, Crotty P, Masaki K, Bojunga J, Bedossa P, Keim V, Wiegand J. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol. 2017 May;66(5):1022-1030. doi: 10.1016/j.jhep.2016.12.022. Epub 2016 Dec 28.
- Individual participant dataSharing planned: No
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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.
Sander Lefere, dr. contact
Patrick Calders, Prof. dr. principal investigator
University Ghent
Anja Geerts, Prof. dr. principal investigator
University Hospital, Ghent
Sander Lefere, dr. study chair
University Ghent
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Combined aerobic + strength training and Combined strength + HIIT training in people with Exercise Therapy and Metabolic Dysfunction-associated Steatotic Liver Disease, run by University Ghent at 1 site in Belgium.
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 3 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: status not confirmed, as of the sponsor's last update on 7 Jun 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 Belgium. 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 Patrick Calders, Prof. dr. (0032498354766, patrick.calders@ugent.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver steatosis by CAP (time frame: before training and after training (14 weeks)). 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 NCT06359444, which also lists 4 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 7 Jun 2024.