Effect of High Intensity Exercise Rehabilitation on Liver Function and Insulin Sensitivity in Patients With MASLD

NCT ID: NCT06359444

Last Updated: 2024-06-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-26
• Study Completion Date: 2026-03-15

Brief 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.

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.

Conditions

Exercise Therapy; Metabolic Dysfunction-associated Steatotic Liver Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Combined strength + HIIT

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.

Group Type: EXPERIMENTAL

Combined strength + HIIT training

Intervention Type: OTHER

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.

Combined strength + aerobic training

The patients in this group will exercise for 14 weeks. It is a combination of strength and aerobic exercise.

Group Type: ACTIVE_COMPARATOR

Combined aerobic + strength training

Intervention Type: OTHER

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.

Interventions

Combined aerobic + strength training

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.

Intervention Type: OTHER

Combined strength + HIIT training

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Ghent

OTHER

Sponsor Role: collaborator

University Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick Calders, Prof. dr.

Role: PRINCIPAL_INVESTIGATOR

University Ghent

Anja Geerts, Prof. dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Sander Lefere, dr.

Role: STUDY_CHAIR

University Ghent

Locations

Ghent University Hospital

Ghent, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Patrick Calders, Prof. dr.

Role: CONTACT

patrick.calders@ugent.be

0032498354766

Sander Lefere, dr.

Role: CONTACT

sander.lefere@ugent.be

Facility Contacts

Anja Geerts, MD, PhD

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 22414768 (View on PubMed)

Hashida 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.

Reference Type: BACKGROUND

PMID: 27639843 (View on PubMed)

Oh 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.

Reference Type: BACKGROUND

PMID: 33898958 (View on PubMed)

Karlas 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.

Reference Type: BACKGROUND

PMID: 28039099 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ONZ-2023-0453

Identifier Type: -

Identifier Source: org_study_id