Clinical trial NCT06359444: Effect of High Intensity Exercise Rehabilitation on Liver Function and Insulin Sensitivity in Patients With MASLD
Official title: Effect of High Intensity Exercise Rehabilitation on Hepatic Fatty Acids (Liver Function), Insulin Sensitivity and Cardiovascular Risk in Patients With MASLD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Exercise Therapy
Metabolic Dysfunction-associated Steatotic Liver Disease
Keywords: exercise
MASLD
liver diseases
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: University Hospital, Ghent
First posted: 2024-04-11
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized in two groups: (a) combined aerobic and strength and (b) combined high intensity and strength.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Liver steatosis by CAP
timeFrame: before training and after training (14 weeks)
measure: Liver steatosis on ultrasound
timeFrame: before training and after training (14 weeks)
Secondary outcomes:
measure: Insulin sensitivity
timeFrame: before training and after training (14 weeks)
measure: Liver transaminases
timeFrame: before training and after training (14 weeks)
measure: Maximal exercise test
timeFrame: before training and after training (14 weeks)
measure: Strength
timeFrame: before training and after training (14 weeks)
measure: Cardiovascular function
timeFrame: before training and after training (14 weeks)
measure: Weight
timeFrame: before training and after training (14 weeks)
measure: Heigth
timeFrame: before training and after training (14 weeks)
measure: BMI
timeFrame: before training and after training (14 weeks)
measure: waist
timeFrame: before training and after training (14 weeks)
measure: BIA
timeFrame: before training and after training (14 weeks)
measure: Interleukine
timeFrame: before training and after training (14 weeks)
measure: TNF-alfa
timeFrame: before training and after training (14 weeks)
measure: Hepatokines
timeFrame: before training and after training (14 weeks)
measure: Myokines
timeFrame: before training and after training (14 weeks)
measure: Adipokines
timeFrame: before training and after training (14 weeks)
measure: SF-36
timeFrame: before training and after training (14 weeks)
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital
Study officials:
affiliation: University Ghent
name: Patrick Calders, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Ghent
name: Anja Geerts, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Ghent
name: Sander Lefere, dr.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.