The Effect of Aerobic and Resistant Exercise Training in Patients With Non-Alcoholic Steatohepatitis

NCT05065593 | Active Not Recruiting DMC

• 1 other identifier: KA- 21027
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The term non-alcoholic fatty liver disease (NAFLD) is used to describe a range of chronic liver diseases that range from steatosis to steatohepatitis, advanced fibrosis, cirrhosis, or excessive alcohol consumption or other causes of steatosis. In this spectrum, Non-Alcoholic Steatohepatitis (NASH), which defines liver damage accompanied by steatosis and inflammation (hepatitis), is one of the most common causes of chronic liver disease worldwide, especially in developed and developing countries, and is present in 15-35% of the general population. Individuals diagnosed with NASH primarily experience deterioration in liver functions, but patients are also affected in terms of vascular structures, immunopathological responses, functional and psychosocial conditions. It is seen that in addition to intrahepatic lipid content, inflammatory markers, liver enzymes, and liver functions, cardiopulmonary endurance, physical activity level, and muscle strength are also affected in these patients, so it is evaluated for the diagnosis and planning of the treatment of the disease. There is no drug with proven efficacy in the treatment of the disease. Since a significant proportion of NASH patients have obesity, Type II Diabetes Mellitus or dyslipidemia, the focus of treatment is to control risk factors or protect the liver from harmful factors such as TNFα. Therefore, the mainstay of treatment, for now, seems to be weight control with a lifestyle change, including regular exercise training and diet control. Exercise intervention is considered an essential component of NAFLD treatment, however; there are a limited number of published articles showing the effects of exercise training in the management of NASH. In addition, the physiological effect of exercise has still not been clarified because NASH is accompanied by metabolic problems such as obesity and T2DM. This study, it is aimed to bring innovation to the literature in understanding the physiological effects of exercise for this disease group by examining the effects of resistance exercise training in addition to aerobic exercise on intrahepatic lipid content, liver functions, inflammatory markers, muscle strength, functionality, and biopsychosocial status in individuals with NASH diagnosis who do not have an additional metabolic problem.

Conditions

Non-Alcoholic Steatohepatitis

Keywords

fibrosis; exercise; inflammation

Outcome Measures

Primary Outcomes (4)

• Change from baseline intrahepatic lipid percentage

  Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) is a MRI-based diagnostic imaging biomarker of the liver, developed in order to facilitate, by enriching, patient recruitment for clinical trials in NASH. The PDFF method is the most objective method for lipid measurement in the liver.

  Change from baseline intrahepatic lipid percentage to 16th week

• Change from baseline hepatic steatosis percentage

  Magnetic Resonance Elastography (MRE) is a technology that combines MRI imaging with low-frequency vibrations to create a visual map (elastogram) that shows the stiffness of body tissues. Currently, MRE is used to detect stiffening of the liver caused by fibrosis and inflammation in chronic liver disease. In chronic liver disease, before reaching the stage of cirrhosis, while detecting fibrosis in the early stages, a tissue stiffness map called elastogram can be drawn. Because the waves can be visualized and analyzed deep in the liver, MRE can evaluate much larger amounts of the total liver than a liver biopsy and has been shown to have high diagnostic accuracy in studies.

  Change from baseline steatosis percentage to 16th week

• Change of liver function parameters level

  Routine liver function test results including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and bilirubin will be measured. All parameters will be recorded in IU/L.The ALT and AST tests measure enzymes that the liver releases in response to damage or disease. The albumin test measures how well the liver creates albumin, while the bilirubin test measures how well it disposes of bilirubin. ALP can be used to evaluate the bile duct system of the liver.

  Change from baseline liver function parameters level to 16th week

• Change of lipid panel

  The lipid panel analysis contains total cholesterol, Low-density lipoprotein (LDL) cholesterol, High-density lipoprotein (HDL) cholesterol, triglycerides. All parameters will be recorded in mg/dL. Higher than normal cholesterol levels are associated with cardiovascular and metabolic diseases. Also, high total cholesterol LDL or triglyceride ratios are associated with NASH. Therefore, the lipid profile is evaluated to monitor NASH progression.

  Change from baseline lipid panel values to 16th week

Secondary Outcomes (12)

• Evaluation of inflammatory markers

  5 minutes, through study completion, an average of 16 weeks, change from baseline inflammatory marker status at 16 weeks.

• Evaluation of aerobic capacity

  12 minutes, through study completion, an average of 16 weeks, change from baseline aerobic capacity at 16 weeks.

• Evaluation of physical activity level

  5 minutes, through study completion, an average of 16 weeks, change from baseline physical activity level at 16 weeks.

• Evaluation of muscle strength

  10 minutes, through study completion, an average of 16 weeks, change from baseline fatique status at 16 weeks

• Evaluation of fatigue

  5 minutes, through study completion, an average of 16 weeks, change from baseline fatique status at 16 weeks

Study Arms (2)

Face-to-Face Training Group

EXPERIMENTAL

After completing all assessments, the intervention group will participate in face-to-face exercise training with a physiotherapist for 3 days for 4 months. In the first week, patients will be taught body awareness; parameters of correct loading on the muscle will be explained and the limits of safe exercise will be drawn. At the beginning and end of all exercises, there will be short-term active stretching and relaxation exercises performed by the patient as a warm-up and cool-down period. In the first 4 weeks, it is planned to increase the physical fitness levels of individuals with progressive resistance exercises and to make them suitable for aerobic loading. For each patient, the PRE, resistance will be increased from 60% to 80% for as long as the person can. At the end of the 1st month, the time allocated to resistance exercise training will be reduced and until the end of the 4th month, an increasing intensity aerobic exercise training will be given on the stationary bike.

Other: resistance and aerobic exercise

Home-Based Control Group

ACTIVE COMPARATOR

After the patients assigned to the control group are evaluated by the physiotherapist with field tests and scales for physical functions, the patients will be informed about the importance of lifestyle changes in disease management, gait training will be given to increase their physical activity level and participants will be asked to follow a 45-minute walking program every day within their own means. All patients in the control group will be followed up regularly and their activity levels will be questioned in interim evaluations by asking them to keep a weekly physical activity diary.

Other: physical activity recommendation

Interventions

resistance and aerobic exercise OTHER

Resistive exercises allow loading the muscle under suitable conditions with various weights or resistances. In order to increase the level of physical fitness with the increase of muscle strength and bone mass in individuals, resistance exercises were preferred. Aerobic exercises, on the other hand, are a special type of exercise that develops both the musculoskeletal system and the cardiovascular system, which includes large muscle groups and should be performed for at least 20 minutes when the heart rate accelerates at certain rates. Aerobic exercise was preferred in order to increase cardiovascular endurance, accelerate fat burning and reduce fatigue.

Face-to-Face Training Group

physical activity recommendation OTHER

Patients will be informed about the importance of lifestyle change in disease management, walking training will be given to increase their physical activity level, and participants will be asked to follow a 45-minute walking program every day within their own means.

Home-Based Control Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Having been diagnosed with NASH according to the diagnostic criteria determined by the American Gastroenterology Society / Asia-Pacific Working Group,
• No history of hepatic decompensation such as hepatic encephalopathy or abdominal ascites,
• Not being obese according to the criteria of the World Health Organization (Body Mass Index (BMI) \<30),
• HbA1c value \<6.5%,
• No changes in blood pressure, hyperlipidemia drugs in the last 3 months,
• Absence of any mental disorder or exercise compliance problem that would prevent them from participating in the study.
• It was determined as being voluntary to participate in the study.

You may not qualify if:

• A history of liver disease other than NASH, such as acute or chronic viral hepatitis, autoimmune hepatitis,
• Alcohol consumption \>30 g/day in men and \>20 g/day in women,
• Having regular exercise habits,
• Presence of conditions where exercise is contraindicated, such as unstable ischemia, decompensated heart failure, arrhythmia that increases with exercise and cannot be controlled, severe aortic stenosis, hypertrophic cardiomyopathy,
• Having orthopedic problems that limit lower extremity movements such as previous cerebrovascular disease, neurological diseases that cause cognitive and motor loss such as Alzheimer's and Parkinson's, and endoprosthesis surgery in the last three months, permanent joint contracture,
• Regular use of food supplements,
• It was determined that he did not volunteer to participate in the study.

Sponsors & Collaborators

• Hacettepe University: lead

Study Sites (1)

Hacettepe University, Faculty of Physical Therapy and Rehabilitation

Ankara, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fibrosis; Motor Activity; Inflammation

Interventions

Exercise

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistant, Physiotherapist

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: October 4, 2021
• Study Start: September 30, 2021
• Primary Completion: January 30, 2024
• Study Completion: January 30, 2025
• Last Updated: June 28, 2024

Record last verified: 2024-06

Locations

TU (1)