Effects of High-Intensity Interval Training Exercise in Adolescents With Hepatosteatosis

Study Overview
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Brief Summary
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This is a research study about how short-term exercise intervention affects adolescents with a disease called non-alcoholic fatty liver disease (NAFLD).

Detailed Description
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The study investigators want to learn more about the effect of a type of exercise on non-alcoholic fatty liver disease (NAFLD), and on markers of health (for example, liver, heart, and overall health) and how the body uses energy in teenagers. The exercise we are studying is called high-intensity interval training, or HIIT. Some participants in this study will receive a 4-week exercise program, and the others will not.

Official Title
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Effects of High-Intensity Interval Training Exercise in Adolescents With Hepatosteatosis

Conditions
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Non-Alcoholic Fatty Liver Disease, Insulin Resistance, High Intensity Interval Training, Childhood Obesity

Intervention / Treatment
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* Other: High-Intensity Interval Training (HIIT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Initial Enrollment Ages 13-18 years (inclusive) for both sexes Any ethnic/racial background English speaking competence Teenagers ages 13-15 weighing more than 145 pounds OR teenagers ages 16-18 weighing more than 170 pounds Low risk to participate in an exercise program as determined by The Physical Activity Readiness Questionnaire for Everyone Late stages of puberty (i.e., Tanner stage IV or V) based on Tanner Staging. Inclusion Criteria: Control or Exercise Group Presence of Non-Alcoholic Fatty Liver Disease (NAFLD) as determined by FibroScan Controlled Attenuated Parameter (CAP) score Confirmed lack of diabetes as determined by Oral Glucose Tolerance Test (OGTT) Confirmed eligibility per medical history Exclusion criteria: Pre-pubertal or early stages of puberty Pregnancy Confirmed lack of NAFLD in the past 6 months via biopsy or MRI Presence of an implantable medical device or metal objects in the body (a contraindication for FibroScan and/or MRI) High-risk to participate in an exercise program as determined by The Physical Activity Readiness Questionnaire for Everyone Unable to cooperate with study procedures and tests including genetic or physical conditions impacting mobility over the past year Having known chronic illnesses/disorders that may independently affect study outcome measures: type 1 diabetes mellitus, type 2 diabetes, neurologic (e.g., epilepsy), developmental (developmental delay, autism spectrum disorder), endocrine (Cushing's, growth hormone deficiency), hepatic (other than NAFLD), autoimmune, cardiac and renal disorders Current history of poorly-controlled asthma. Taking any of the following medications that can affect study outcome at the time of enrollment: insulin, metformin, or any other anti-diabetics, antipsychotics, oral steroids, and anabolic drugs (growth hormone replacement therapy, testosterone, and oxandrolone). Adolescents who have a history of claustrophobia. Adolescents who need sedation in order to complete MRI. Adolescents determined ineligible by the study investigator or delegated staff.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise Group<br>Study participants in this group will be asked to complete 4 weeks of high-intensity interval training (HIIT). | Other: High-Intensity Interval Training (HIIT)<br>* The exercise we are studying is called high-intensity interval training, or HIIT. Participants in the exercise group will participate in the exercise program. Each exercise session will last up to 1 hour. All exercise sessions will be directed and monitored by an experienced exercise trainer or exercise physiologist.<br>|
| No Intervention: Control Group<br>Study participants in this group will not undergo HIIT exercise training during this study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intrahepatic triglyceride (IHTG) | Intrahepatic triglyceride (IHTG) percent (%) will be measured via Magnetic Resonance Imaging (MRI). IHTG percent can theoretically range between 0 and 100. By definition, an individual has Non-Alcoholic Fatty Liver Disease (NAFLD) when the IHTG percent is at or above 5 percent. | 24 months | 
| Cardiovascular fitness | Cardiovascular fitness will be assessed via peak oxygen uptake (VO2 max). VO2 max is expressed as milliliters per body weight in kilograms per minutes. There is no established normative data for VO2 max in pediatric population; however, higher values indicate better cardiovascular fitness. | 24 months | 
| HOMA-IR | The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) will be calculated using the fasting glucose and insulin levels. Higher HOMA-IR values indicate greater insulin resistance. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alanine Aminotransferase | Serum alanine aminotransferase (ALT) level will be measured. Higher ALT levels suggest presence of hepatocellular damage. | 24 months | 
| FibroScan - Controlled Attenuated Parameter | Controlled Attenuated Parameter (CAP) score will be measured using FibroScan. CAP score is reported in decibel/second (dB/s) and ranges between 100-400. A score of 241 dB/s or greater is consistent with non-alcoholic fatty liver disease. | 24 months | 
| FibroScan - Transient Elastogram | Transient Elastogram (TE) score will be measured using FibroScan. TE score is reported in kilopascals (kPa) and ranges between 0-75. A score of 8.5 kPa or greater is consistent with fibrotic liver disease. | 24 months | 
| Body Composition - Total Body Fat and Visceral Fat | Body composition will be measured using Dual X-Ray Absorptiometry (DXA) scan. Normative data for total body fat and visceral fat are not established; however, larger visceral fat volume is linked to higher intrahepatic triglyceride content and insulin resistant state; similarly, larger total body fat volume is linked to higher intrahepatic triglyceride content and insulin resistant state. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Steatosis, NAFLD, HIIT, Insulin, Fitness, Controlled Attenuated Parameter, Peak oxygen uptake