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

Hepatitis B, Chronic Clinical Trial

— FitLiver  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05265026
• Other study ID #: H-21034236
• Status: Completed
• Phase: N/A
• Start date: March 14, 2022
• Est. completion date: October 1, 2023

Study information

• Verified date: October 2023
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: October 1, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Hepatic Steatosis
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Behavioral:
• High Intensity Interval Training
A training session consists of 40 minutes as follows: 4x4 minutes at > 85% of heart rate maximum (HRmax) alternated by 3x3 minutes active recovery at (50-70% of HRmax) and a 10-min-warm-up (60-79% of HRmax) and 5- minute cool-down at ~ warm up intensity. HRmax was determined during the VO2max test at baseline visit. Minutes spent in the different heart rate zones is monitored during the session (zone 1: 60-69%, zone 2: 70-74%, zone 3: 75-79%, zone 4: 80-84%, zone 5: >85% of HRmax).

Locations

Country	Name	City	State
Denmark	Centre for Physical Activity Research	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Copenhagen University Hospital, Hvidovre

Country where clinical trial is conducted

Denmark, 

Outcome

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