Aerobic Exercise Training in Patients With Chronic Hepatitis B and Hepatic Steatosis

Not Applicable

Completed

• Conditions: Hepatitis B, Chronic; Hepatic Steatosis
• Interventions: Behavioral: High Intensity Interval Training

• Registration Number: NCT05265026
• Lead Sponsor: Rigshospitalet, Denmark

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.

Study Timeline

• Study First Submitted: 2022-02-11
• Study First Submitted QC: 2022-02-22
• Study First Posted: 2022-03-03
• Study Start: 2022-03-14
• Primary Completion: 2023-09-30
• Status Verified: 2023-10
• Study Completion: 2023-10-01
• Last Update Submitted: 2023-10-26
• Last Update Posted: 2023-10-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exercise Intervention Arm	High Intensity Interval Training	Three high intensity interval exercise sessions per week of 40 minutes duration per session. Exercise will be performed on ergometerbikes.

Primary Outcome Measures

Name	Time	Method
Fat-Fraction of the Liver	From baseline to follow-up at 12 weeks	Hepatic fat-fraction measured by MRI with IDEAL-IQ (%)

Secondary Outcome Measures

Name	Time	Method
Hepatitis B virus (DNA)	From baseline to follow-up at 12 weeks	Hepatitis B virus (DNA) (IU/mL)
Follistatin secretion	From baseline to follow-up at 12 weeks	Follistatin (ng/L) secretion during a hormone infusion of somatostatin and glucagon
Fibroblast growth factor 21 (FGF21) secretion	From baseline to follow-up at 12 weeks	FGF21 (ng/L) secretion during a hormone infusion of somatostatin and glucagon
Growth/differentiation factor 15 (GDF15) secretion	From baseline to follow-up at 12 weeks	GDF15 (ng/L) secretion during a hormone infusion of somatostatin and glucagon
Angiopoietin-like 4 (ANGPTL4) secretion	From baseline to follow-up at 12 weeks	ANGPTL4 (μg/L) secretion during a hormone infusion of somatostatin and glucagon
C-reactive protein (CRP) secretion	From baseline to follow-up at 12 weeks	CRP (mg/L) secretion during a hormone infusion of somatostatin and glucagon
Interleukin-8 secretion	From baseline to follow-up at 12 weeks	Interleukin-8 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon
TNFα secretion	From baseline to follow-up at 12 weeks	TNFα (pg/mL) secretion during a hormone infusion of somatostatin and glucagon
Visceral fat	From baseline to follow-up at 12 weeks	Visceral fat assessed by MRI (kg)
Total fat mass	From baseline to follow-up at 12 weeks	Total fat mass assessed by DXA scan (kg)
Interferon-ϒ secretion	From baseline to follow-up at 12 weeks	Interferon-ϒ (pg/mL) secretion during a hormone infusion of somatostatin and glucagon
Interleukin-10 secretion	From baseline to follow-up at 12 weeks	Interleukin-10 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon
Interleukin-6 secretion	From baseline to follow-up at 12 weeks	Interleukin-6 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon
Interleukin-1 secretion	From baseline to follow-up at 12 weeks	Interleukin-1 (pg/mL) secretion during a hormone infusion of somatostatin and glucagon
Total free fat mass	From baseline to follow-up at 12 weeks	Total free fat mass assessed by DXA scan (kg)
Total lean body mass	From baseline to follow-up at 12 weeks	Total lean body mass assessed by DXA scan (kg)
Physical fitness (VO2max)	From baseline to follow-up at 12 weeks	Physical fitness assessed by VO2max (mL/kg/min)
Fasting glucose	From baseline to follow-up at 12 weeks	Fasting glucose (mmol/L)
Body weight	From baseline to follow-up at 12 weeks	Body weight (kg)
Blood pressure measurements	From baseline to follow-up at 12 weeks	Systolic blood pressure (mmHg) and diastolic blood pressure (mmHg)
Total physical activity	From baseline, at 6 weeks to follow-up at 12 weeks	Total physical activity assessed by activity monitor (hours, minutes)
Moderate and vigorous physical activity (MVPA)	From baseline, at 6 weeks to follow-up at 12 weeks	Moderate and vigorous physical activity (MVPA) activity monitor (hours, minutes)
Glycated haemoglobin type 1AC (HbA1c)	From baseline to follow-up at 12 weeks	Glycated haemoglobin type 1AC (HbA1c) (mmol/mL)
Fasting Insulin	From baseline to follow-up at 12 weeks	Fasting Insulin (pmol/L)
Lipid measurements	From baseline to follow-up at 12 weeks	Total cholesterol (mmol/L), total triglyceride (mmol/L), low density lipoprotein (LDL) (mmol/L), high density lipoprotein (HDL) (mmol/L)
Alanine transaminase (ALT)	From baseline to follow-up at 12 weeks	Alanine transaminase (ALT) (U/L)
Fibrosis-4 (FIB-4)	From baseline to follow-up at 12 weeks	Fibrosis-4 (FIB-4)
International Normalised Ratio (INR)	From baseline to follow-up at 12 weeks	International Normalised Ratio (INR)
Sedentary time (SED)	From baseline, at 6 weeks to follow-up at 12 weeks	Sedentary time (SED) activity monitor (hours, minutes)
Oral glucose tolerance test	From baseline to follow-up at 12 weeks	Oral glucose tolerance test (mmol/L)
Aspartate transaminase (AST)	From baseline to follow-up at 12 weeks	Aspartate transaminase (AST) (U/L)

Trial Locations

Locations (1)

Centre for Physical Activity Research; 🇩🇰 Copenhagen, Denmark