Childhood Obesity, High Intensity Interval Training, Insulin Resistance, Non-Alcoholic Fatty Liver Disease
Conditions
Keywords
NAFLD, HIIT, Insulin, Fitness, Controlled Attenuated Parameter, Steatosis, Peak oxygen uptake
Brief summary
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
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.
Interventions
OTHERHigh-Intensity Interval Training (HIIT)
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.
Sponsors
National Institute of General Medical Sciences (NIGMS)
Arkansas Children's Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 18 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intrahepatic Triglyceride (IHTG) | 4 weeks | 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. |
| Cardiovascular Fitness | 4 weeks | Cardiovascular fitness will be assessed via peak oxygen uptake (VO2 max). VO2 max is expressed as milliliters per body weight per minute in kilograms of lean body mass (mL/min/kg per LBM). There is no established normative data for VO2 max in pediatric population; however, higher values indicate better cardiovascular fitness. |
| HOMA-IR | 4 weeks | 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. HOMA-IR is calculated as fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. HOMA-IR has an arbitrary unit. Higher numbers suggest worse outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alanine Aminotransferase | 4 weeks | Serum alanine aminotransferase (ALT) level will be measured. ALT level is reported in international unit/liter or IU/L. Higher ALT levels suggest presence of hepatocellular damage. |
| Body Composition - Total Body Fat | 4 weeks | Body composition will be measured using Dual X-Ray Absorptiometry (DXA) scan. Normative data for total body fat is not established; however, larger total body fat percentage (percentage of total body weight) is linked to higher intrahepatic triglyceride content and insulin resistant state. |
| FibroScan - Controlled Attenuated Parameter | 4 weeks | Controlled Attenuated Parameter (CAP) score will be measured using FibroScan. CAP score is reported in decibel/meter (dB/m) and ranges between 100-400. A score of 241 dB/m or greater is consistent with non-alcoholic fatty liver disease. |
| FibroScan - Transient Elastogram | 4 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exercise Group Study participants in this group will be asked to complete 4 weeks of high-intensity interval training (HIIT).
High-Intensity Interval Training (HIIT): 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. | 34 |
| Control Group Study participants in this group will not undergo HIIT exercise training during this study. | 6 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 |
Baseline characteristics
| Characteristic | Control Group | Total | Exercise Group |
|---|---|---|---|
| Age, Continuous | 15.4 years STANDARD_DEVIATION 1 | 15.2 years STANDARD_DEVIATION 1.4 | 15.2 years STANDARD_DEVIATION 1.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 18 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 22 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 17 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 23 Participants | 17 Participants |
| Sex: Female, Male Female | 4 Participants | 24 Participants | 20 Participants |
| Sex: Female, Male Male | 2 Participants | 16 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 6 |
| other Total, other adverse events | 1 / 34 | 0 / 6 |
| serious Total, serious adverse events | 0 / 34 | 0 / 6 |
Outcome results
Primary
Cardiovascular Fitness
Cardiovascular fitness will be assessed via peak oxygen uptake (VO2 max). VO2 max is expressed as milliliters per body weight per minute in kilograms of lean body mass (mL/min/kg per LBM). There is no established normative data for VO2 max in pediatric population; however, higher values indicate better cardiovascular fitness.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise Group | Cardiovascular Fitness | 40.8 mL/min/kg of Lean Body Mass | Standard Error 7.3 |
| Control Group | Cardiovascular Fitness | 43.2 mL/min/kg of Lean Body Mass | Standard Error 7.2 |
p-value: 0.633ANCOVA
Primary
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. HOMA-IR is calculated as fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. HOMA-IR has an arbitrary unit. Higher numbers suggest worse outcomes.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise Group | HOMA-IR | 8.69 arbitrary unit | Standard Deviation 5.5 |
| Control Group | HOMA-IR | 6.4 arbitrary unit | Standard Deviation 5.5 |
p-value: 0.433ANCOVA
Primary
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise Group | Intrahepatic Triglyceride (IHTG) | 5.26 percentage of IHTG | Standard Deviation 3.01 |
| Control Group | Intrahepatic Triglyceride (IHTG) | 8.97 percentage of IHTG | Standard Deviation 6.61 |
p-value: 0.363ANCOVA
Secondary
Alanine Aminotransferase
Serum alanine aminotransferase (ALT) level will be measured. ALT level is reported in international unit/liter or IU/L. Higher ALT levels suggest presence of hepatocellular damage.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise Group | Alanine Aminotransferase | 20.1 international unit/liter | Standard Error 17.6 |
| Control Group | Alanine Aminotransferase | 29.7 international unit/liter | Standard Error 17.6 |
p-value: 0.822ANCOVA
Secondary
Body Composition - Total Body Fat
Body composition will be measured using Dual X-Ray Absorptiometry (DXA) scan. Normative data for total body fat is not established; however, larger total body fat percentage (percentage of total body weight) is linked to higher intrahepatic triglyceride content and insulin resistant state.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise Group | Body Composition - Total Body Fat | 45.35 percentage of total body weight | Standard Deviation 6.18 |
| Control Group | Body Composition - Total Body Fat | 44.05 percentage of total body weight | Standard Deviation 6.18 |
p-value: 0.921ANCOVA
Secondary
FibroScan - Controlled Attenuated Parameter
Controlled Attenuated Parameter (CAP) score will be measured using FibroScan. CAP score is reported in decibel/meter (dB/m) and ranges between 100-400. A score of 241 dB/m or greater is consistent with non-alcoholic fatty liver disease.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise Group | FibroScan - Controlled Attenuated Parameter | 279 decibel/meter | Standard Deviation 35 |
| Control Group | FibroScan - Controlled Attenuated Parameter | 280 decibel/meter | Standard Deviation 35 |
p-value: 0.554ANCOVA
Secondary
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise Group | FibroScan - Transient Elastogram | 5 kPa | Standard Deviation 1 |
| Control Group | FibroScan - Transient Elastogram | 5 kPa | Standard Deviation 3 |
p-value: 0.186ANCOVA