Different Exercise Modalities in the Treatment of NAFLD and Their Impact on Myokines

Investigation of Effectiveness of Different Exercise Types, and Their Therapeutic Effect Mechanisms and the Roles of Motivational Interview in the Treatment of Non-Alcoholic Fatty Liver Disease

The goal of this 12-week clinical trial is to investigate the effectiveness of different exercise types in treating Non-Alcoholic Fatty Liver Disease (NAFLD) and to explore their impact on myokine levels associated with lipid metabolism. The main questions it aims to answer are:

1. How does the type and dose of exercise affect the treatment of NAFLD?
2. What is the influence of exercise interventions in NAFLD treatment on myokine levels related to lipid metabolism?
3. How does motivational interviewing contribute to lifestyle modification in the treatment of NAFLD?

Participants in this study will engage in assigned exercise routines randomly, including HIIT, resistance training, or FATmax exercises. Additionally, motivational interviewing techniques will be employed to assess their impact on lifestyle changes. Researchers will compare the outcomes among the different exercise groups, along with a control group receiving only standard care for NAFLD. This comparison aims to determine the respective effects of these interventions on both NAFLD and associated myokine levels.

Study Overview

• Status: Recruiting
• Conditions: Fatty Liver; NAFLD; Nonalcoholic Fatty Liver Disease; Fatty Liver, Nonalcoholic
• Intervention / Treatment: Other: Exercise; Behavioral: Motivational Interviewing

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mehtap Kaçar, MD, PhD, Prof; Phone Number: 1419 +90 (216) 578 00 00; Email: mehtap.kacar@yeditepe.edu.tr
• Study Contact Backup: Name: Meltem Yalçın Oğuz, MSc, Pt; Phone Number: 1533 +90 (216) 578 00 00; Email: meltem.yalcin@yeditepe.edu.tr

Study Locations

• Turkey
  • Ataşehir
    • Istanbul, Ataşehir, Turkey, 34755
      • Recruiting
      • Yeditepe University
      • Contact: Meltem Yalçın Oğuz, MSc, Pt; Phone Number: 1533 +90 (216) 578 00 00; Email: meltem.yalcin@yeditepe.edu.tr
      • Contact: Burçin Tuvana Us, MD; Phone Number: 1533 +90 (216) 578 00 00; Email: tuvana.us@yeditepe.edu.tr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have received a diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD)
• Age between 25 and 50 years old
• Use of smartphone
• Fall into category A or B according to the American Heart Association Risk Assessment Criteria

Exclusion Criteria:

• Viral hepatitis
• Excessive alcohol consumption (more than 30 grams per day for men and more than 20 grams per day for women)
• Use of specific medications: amiodarone, corticosteroids, methotrexate, tamoxifen, synthetic estrogen, valproic acid, intravenous tetracycline, and highly active antiretroviral drugs
• Presence of accompanying chronic diseases such as Wilson's disease, hemochromatosis, and celiac disease
• Liver storage diseases
• Cancer
• Cirrhosis
• Advanced changes in liver ultrasonography evaluations, such as fibrosis
• Presence of other chronic diseases (kidney failure, heart failure, atherosclerotic heart disease, hypertension, arrhythmia disorders)
• BMI greater than 40 kg/m²
• History of surgery or trauma in the last 6 months
• Orthopedic and/or neurological impairment
• Health problems that may hinder participation in the exercise program
• Regular and continuous participation in sports or exercise at least 3 times a week for the past 3 years
• Family history of coronary artery disease (coronary artery disease before the age of 45 in male first-degree relatives and other male relatives, or before the age of 65 in female first-degree relatives and other female relatives)
• Presence of specific symptoms during medical history or physical examination: chest pain radiating to the neck, jaw, or arm, shortness of breath during rest or physical activity, dizziness, fainting, orthopnea or paroxysmal nocturnal dyspnea, ankle edema, palpitations or tachycardia, intermittent claudication, heart murmur, unexplained excessive fatigue
• Fall into category C or D according to the American Heart Association Risk Assessment Criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group; This group will consist of individuals with liver fat accumulation under standard care and no exercise intervention will be implemented.
Experimental: Fatmax Exercise Group; Individuals with liver fat accumulation under standard care will have their Fatmax values calculated and an exercise prescription will be designed accordingly.	Other: Exercise; The exercise interventions in this study include High-Intensity Interval Training (HIIT), involving brief bursts of intense exercise; Resistance Exercise, focusing on strength and muscle endurance; and Fatmax Exercise, tailored to optimize fat oxidation during aerobic activity.
Experimental: Fatmax Exercise and Motivational Interviewing Group; In addition to the prescription of Fatmax exercise for individuals with liver fat accumulation under standard care, motivational interviewing principles will be applied.	Other: Exercise; The exercise interventions in this study include High-Intensity Interval Training (HIIT), involving brief bursts of intense exercise; Resistance Exercise, focusing on strength and muscle endurance; and Fatmax Exercise, tailored to optimize fat oxidation during aerobic activity.; Behavioral: Motivational Interviewing; Motivational Interviewing will be employed as a counseling technique to elicit behavior change by fostering collaborative and empathetic conversations, enhancing motivation for positive lifestyle modifications in individuals with liver fat accumulation.
Experimental: HIIT Group; Individuals with liver fat accumulation under standard care will be provided with a High-Intensity Interval Training (HIIT) exercise prescription.	Other: Exercise; The exercise interventions in this study include High-Intensity Interval Training (HIIT), involving brief bursts of intense exercise; Resistance Exercise, focusing on strength and muscle endurance; and Fatmax Exercise, tailored to optimize fat oxidation during aerobic activity.
Experimental: HIIT and Motivational Interviewing Group; In addition to formulating a High-Intensity Interval Training (HIIT) exercise prescription for individuals with liver fat accumulation under standard care, motivational interviewing principles will be applied.	Other: Exercise; The exercise interventions in this study include High-Intensity Interval Training (HIIT), involving brief bursts of intense exercise; Resistance Exercise, focusing on strength and muscle endurance; and Fatmax Exercise, tailored to optimize fat oxidation during aerobic activity.; Behavioral: Motivational Interviewing; Motivational Interviewing will be employed as a counseling technique to elicit behavior change by fostering collaborative and empathetic conversations, enhancing motivation for positive lifestyle modifications in individuals with liver fat accumulation.
Experimental: Resistance Exercise Group; Individuals with liver fat accumulation under standard care will be provided with a resistance exercise prescription.	Other: Exercise; The exercise interventions in this study include High-Intensity Interval Training (HIIT), involving brief bursts of intense exercise; Resistance Exercise, focusing on strength and muscle endurance; and Fatmax Exercise, tailored to optimize fat oxidation during aerobic activity.
Experimental: Resistance Exercise and Motivational Interviewing Group; In addition to formulating a resistance exercise prescription for individuals under standard care with liver fat accumulation, motivational interviewing principles will be applied.	Other: Exercise; The exercise interventions in this study include High-Intensity Interval Training (HIIT), involving brief bursts of intense exercise; Resistance Exercise, focusing on strength and muscle endurance; and Fatmax Exercise, tailored to optimize fat oxidation during aerobic activity.; Behavioral: Motivational Interviewing; Motivational Interviewing will be employed as a counseling technique to elicit behavior change by fostering collaborative and empathetic conversations, enhancing motivation for positive lifestyle modifications in individuals with liver fat accumulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the liver steatosis grade	Changes in the level of liver fat accumulation in radiological abdominal ultrasonography (USG) will be observed. The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ALT	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
AST	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
GGT	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
Free fatty acids	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
Triglycerides	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
HDL	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
LDL	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
Total cholesterol	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
CRP	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
ESR	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
Changes in body weight	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
Changes in lean body mass	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
Changes in body fat percentage	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
Changes in body mass index	The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
Changes in waist-to-hip ratio	The waist and hip measurements will be taken twice with a tape measure. The results will be aggregated to arrive at one reported value as a waist-to-hip ratio. This is calculated as waist measurement divided by hip measurement (W⁄H). The difference between the values obtained at the beginning of the study and those measured after completing the program will be evaluated. Data collected at the beginning and end of the study will be compared.	12-week
Changes in peak oxygen consumption	At the beginning, every 4 weeks, and at the end of the study, peak oxygen consumption measurement will be conducted through the cardiopulmonary exercise test. Data collected at the beginning and end of the study will be compared.	12-week
Changes in peak heart rate	At the beginning, every 4 weeks, and at the end of the study, peak heart rate measurement will be conducted through the cardiopulmonary exercise test. Data collected at the beginning and end of the study will be compared.	12-week
Changes in anaerobic threshold	At the beginning, every 4 weeks, and at the end of the study, anaerobic threshold measurements will be conducted through the cardiopulmonary exercise test. Data collected at the beginning and end of the study will be compared.	12-week
Changes in basal metabolic rate	Basal metabolic rate measurements will be conducted twice using an indirect calorimeter, once at the beginning and once at the end of the study. Data collected at the beginning and end of the study will be compared.	12-week
Changes in muscle strength analysis results	At the beginning and end of the study, the maximum isometric contraction strength of the hand and forearm muscles will be measured using a hand dynamometer. Data collected at the beginning and end of the study will be compared.	12-week
Changes in The 5 Times Sit-to-Stand Test results	The 5 Times Sit-to-Stand Test will be administered as a balance test. Data collected at the beginning and end of the study will be compared.	12-week
Changes in Single Leg Standing Test results	The Single Leg Standing Test will be administered as a balance test. Data collected at the beginning and end of the study will be compared.	12-week
Changes in FATmax levels	At the beginning and end of the study, participants' FATmax levels will be determined through the FATmax test. Data collected at the beginning and end of the study will be compared.	12-week
Changes in Healthy Lifestyle Habits Scale II scores	At the beginning and end of the study, a total of two administrations of the questionnaires will be conducted. Data collected at the beginning and end of the study will be compared.	12-week
Changes in Short Form Survey (SF-36) scores	At the beginning and end of the study, a total of two administrations of the questionnaires will be conducted. Data collected at the beginning and end of the study will be compared.	12-week
Changes in Beck Depression Scale scores	At the beginning and end of the study, a total of two administrations of the questionnaires will be conducted. Data collected at the beginning and end of the study will be compared.	12-week
Changes in Pittsburgh Sleep Quality Index scores	At the beginning and end of the study, a total of two administrations of the questionnaires will be conducted. Data collected at the beginning and end of the study will be compared.	12-week
Changes in the serum levels of myokines	Serum samples will be obtained twice, at the beginning and end of the study. Musclin, myonectin, and myostatin levels will be measured using ELISA, while measurements of BAIBA will be conducted using Liquid Chromatography Spectrometry. Data collected at the beginning and end of the study will be compared.	12-week

Collaborators and Investigators

• Sponsor: Yeditepe University
• Collaborators: Tübitak

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2024
• Primary Completion (Estimated): September 15, 2024
• Study Completion (Estimated): October 15, 2024

Study Registration Dates

• First Submitted: January 5, 2024
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Exercise; Motivational Interviewing; NAFLD; HIIT; Resistance Exercise; Myokine; Fatmax Intensity
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: TBTK-MK-2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No