Clinical trial NCT05265026: Aerobic Exercise Training in Patients With Chronic Hepatitis B and Hepatic Steatosis
Official title: Effect of Aerobic Exercise Training on Fat-fraction of the Liver in Patients With Chronic Hepatitis B and Hepatic Steatosis: a Randomised Controlled Intervention Trial. The Fit Liver Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatitis B, Chronic
Hepatic Steatosis
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Copenhagen University Hospital, Hvidovre
First posted: 2022-03-03
Enrollment: 19
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomised, controlled, unblinded, clinical intervention trial consisting of 12 weeks of aerobic exercise training. Thirty persons with chronic hepatitis B (CHB) and hepatic steatosis are randomised to either aerobic exercise training (intervention group, n=15) or no intervention (control group, n=15). The study will investigate the effects of the exercise intervention on the liver and the hypothesis is that the exercise group will reduce the fat-fraction of the liver after the intervention.

Detailed description: Primary aim: To investigate whether regular aerobic exercise training will decrease the fat-fraction of the liver in persons with CHB and hepatic steatosis shown by magnetic resonance imaging (MRI) by use of Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL-IQ).

Secondary aim: To investigate the effects of aerobic exercise training on hepatokine secretion in persons with CHB and hepatic steatosis. Also, to investigate if regular physical exercise will improve lipid- and glucose metabolism, liver status, markers of inflammation, body composition, and blood pressure.

Study participants will undergo pre and post the interventioon: Clinical examination with ECG, blood pressure measurements, blood sampling, oral glucose tolerance test, a hormone infusion of somatostatin and glucagon, -increasing the glucagon/insulin ratio mimicking an acute exercise bout, measuring the effect on circulating hepatokines and cytokines, fibroscan, VO2-max test, DXA scan, AX3 activity monitoring, nail fold capillaryscopy, IQOLA SF-36 and IPAQ-SF questionnaire, 24H food intake registration, MRI scan of the liver and optional liver biopsy. 6 and 12 months follow-up is planned.

The exercise intervention will be randomised 1:1 with no stratification: The training program includes three weekly supervised training sessions of 40 minutes/session over 12 weeks. Participants are instructed not to change their lifestyles during the intervention.

Eligibility criteria: Inclusion Criteria:

* Chronic hepatitis B defined by HBsAg positive \>6 months
* Positive HBV-DNA
* Age \>30
* Hepatic steatosis diagnosed by Controlled Attenuated Parameter (CAP) \>250 assessed by Transient Elastography or by ultrasound defined hepatic steatosis

Exclusion Criteria:

* HIV, HCV, HDV-co infection
* Primary biliary cholangitis
* Wilsons Disease
* Autoimmune hepatitis
* Hepatocellular carcinoma
* Antiviral medication
* Steatogenic medication (systemic corticosteroids, amiodarone, tamoxifen, valproic acid, and methotrexate)
* Average alcohol intake \>30 g for men and \>20 g for women pr. day
* Contraindications for MRI scan
* Coronary artery disease contraindicating HIIT
* Unable to understand and read written information for participants written consent
* Pregnancy

Primary outcomes:
measure: Fat-Fraction of the Liver
timeFrame: From baseline to follow-up at 12 weeks
Secondary outcomes:
measure: Fibroblast growth factor 21 (FGF21) secretion
timeFrame: From baseline to follow-up at 12 weeks
measure: Follistatin secretion
timeFrame: From baseline to follow-up at 12 weeks
measure: Growth/differentiation factor 15 (GDF15) secretion
timeFrame: From baseline to follow-up at 12 weeks
measure: Angiopoietin-like 4 (ANGPTL4) secretion
timeFrame: From baseline to follow-up at 12 weeks
measure: C-reactive protein (CRP) secretion
timeFrame: From baseline to follow-up at 12 weeks
measure: Interferon-ϒ secretion
timeFrame: From baseline to follow-up at 12 weeks
measure: Interleukin-10 secretion
timeFrame: From baseline to follow-up at 12 weeks
measure: Interleukin-8 secretion
timeFrame: From baseline to follow-up at 12 weeks
measure: Interleukin-6 secretion
timeFrame: From baseline to follow-up at 12 weeks
measure: Interleukin-1 secretion
timeFrame: From baseline to follow-up at 12 weeks
measure: TNFα secretion
timeFrame: From baseline to follow-up at 12 weeks
measure: Visceral fat
timeFrame: From baseline to follow-up at 12 weeks
measure: Total fat mass
timeFrame: From baseline to follow-up at 12 weeks
measure: Total free fat mass
timeFrame: From baseline to follow-up at 12 weeks
measure: Total lean body mass
timeFrame: From baseline to follow-up at 12 weeks
measure: Body weight
timeFrame: From baseline to follow-up at 12 weeks
measure: Blood pressure measurements
timeFrame: From baseline to follow-up at 12 weeks
measure: Physical fitness (VO2max)
timeFrame: From baseline to follow-up at 12 weeks
measure: Total physical activity
timeFrame: From baseline, at 6 weeks to follow-up at 12 weeks
measure: Moderate and vigorous physical activity (MVPA)
timeFrame: From baseline, at 6 weeks to follow-up at 12 weeks
measure: Sedentary time (SED)
timeFrame: From baseline, at 6 weeks to follow-up at 12 weeks
measure: Hepatitis B virus (DNA)
timeFrame: From baseline to follow-up at 12 weeks
measure: Oral glucose tolerance test
timeFrame: From baseline to follow-up at 12 weeks
measure: Glycated haemoglobin type 1AC (HbA1c)
timeFrame: From baseline to follow-up at 12 weeks
measure: Fasting glucose
timeFrame: From baseline to follow-up at 12 weeks
measure: Fasting Insulin
timeFrame: From baseline to follow-up at 12 weeks
measure: Lipid measurements
timeFrame: From baseline to follow-up at 12 weeks
measure: Alanine transaminase (ALT)
timeFrame: From baseline to follow-up at 12 weeks
measure: Aspartate transaminase (AST)
timeFrame: From baseline to follow-up at 12 weeks
measure: Fibrosis-4 (FIB-4)
timeFrame: From baseline to follow-up at 12 weeks
measure: International Normalised Ratio (INR)
timeFrame: From baseline to follow-up at 12 weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Centre for Physical Activity Research
Study officials:
References: