Obesity and non-alcoholic fatty liver disease (NAFLD) are two related growing epidemics that are becoming pressing public health concerns. High-intensity interval training (HIIT) is a promising cost-effective and time-efficient exercise modality for managing obesity and NAFLD. However, patients with obesity and NAFLD are generally inactive and unfit, and might feel intimidated by the frequency of the prescribed HIIT (conventionally three times weekly). Previous HIIT studies, mostly over 2-4 month periods, showed that the participants could accomplish this exercise frequency under a controlled laboratory environment, but the long-term adherence and sustainability, especially in a field setting, remains uncertain. The situation is more unclear if we also consider those individuals who refused to participate possibly because of their overwhelming perceptions or low self-efficacy toward HIIT. Thus, logically, HIIT at a lower frequency would be practical and more suitable for patients with obesity and NAFLD, but the minimum exercise frequency required to improve health, especially in the long-term, is unknown. This proposed study aims to examine the effectiveness of long-term low-frequency HIIT for improving body adiposity and liver fat in centrally obese adults. The premise of this proposal is supported by recent findings that HIIT performed once a week could improve cardiorespiratory fitness, blood pressure, cardiac morphology, metabolic capacity, muscle power, and lean mass. This study will provide evidence for the benefits of long-term low-frequency HIIT with a follow-up period to assess its effectiveness, safety, adherence, and sustainability. We expect this intervention will enhance the practical suitability of HIIT in inactive obese adults and will provide evidence for low-frequency HIIT as a new exercise option in the management of obesity and NAFLD.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
160
In the high-intensity interval training group, subjects will receive respective prescribed exercise once a week.
In the usual care control group, obesity-related health briefing, dietary caloric restriction advice, and lifestyle counseling/consultation will be provided.
Li Ka Shing Faculty of Medicine, The University of Hong Kong
Hong Kong, Hong Kong
Liver Fat
Intrahepatic triglycerides will be examined by 1H-MR spectroscopy in a 3×3×3 cm voxel using a 1.5-Tesla scanner (SIGNA™ Explorer - 60cm, General Electric Healthcare) housed at the MR imaging unit of HKU core facility. A trained MRI radiographer will operate the machine, position the subjects and analyze the results. NAFLD will be defined as \>5% intrahepatic triglycerides assessed by 1H-MR spectroscopy.
Time frame: Change from baseline amount of intrahepatic triglycerides content at 12 months
Body Adiposity
Total body fat mass will be determined using a full body dual-energy X-ray absorptiometry (DXA) scanner (Explorer S/N 91075, Hologic Inc., Waltham, USA). A trained technician will operate the DXA machine, position the subjects and analyze the results. The typical coefficients of variation of the DXA scanner for each body compartment from duplicate analyses are 0.4% for lean mass, 1.4% for fat mass and 1.0% for bone mass
Time frame: Change from baseline amount of body fat mass at 12 months
Liver Fat
Intrahepatic triglycerides will be examined by 1H-MR spectroscopy in a 3×3×3 cm voxel using a 1.5-Tesla scanner (SIGNA™ Explorer - 60cm, General Electric Healthcare) housed at the MR imaging unit of HKU core facility. A trained MRI radiographer will operate the machine, position the subjects and analyze the results. NAFLD will be defined as \>5% intrahepatic triglycerides assessed by 1H-MR spectroscopy.
Time frame: Change from baseline amount of intrahepatic triglycerides content at 24 months
Body Adiposity
Total body fat mass will be determined using a full body dual-energy X-ray absorptiometry (DXA) scanner (Explorer S/N 91075, Hologic Inc., Waltham, USA). A trained technician will operate the DXA machine, position the subjects and analyze the results. The typical coefficients of variation of the DXA scanner for each body compartment from duplicate analyses are 0.4% for lean mass, 1.4% for fat mass and 1.0% for bone mass
Time frame: Change from baseline amount of body fat mass at 24 months
Visceral Adiposity
Abdominal visceral fat will be measured using a three-point Dixon sequence using a 1.5-Tesla scanner (SIGNA™ Explorer - 60cm, General Electric Healthcare) housed at the MR imaging unit of HKU core facility. A trained MRI radiographer will operate the machine, position the subjects and analyze the results. The abdominal visceral fat between the thoracic diaphragm and the upper bORDER of the first sacral vertebra will be manually marked on each MRI transverse image to calculate the volume of abdominal visceral fat.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Subcutaneous Adiposity
Subcutaneous fat will be measured using a three-point Dixon sequence using 1.5-Tesla scanner (SIGNA™ Explorer - 60cm, General Electric Healthcare) housed at the MR imaging unit of HKU core facility. A trained MRI radiographer will operate the machine, position the subjects and analyze the results. The abdominal subcutaneous fat between the thoracic diaphragm and the upper border of the first sacral vertebra will be manually marked on each MRI transverse
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Body Mass Index
A calibrated electronic digital weighing scale (UC321, A\&D Medical) with a capacity from 0.05kg to 150kg (± 0.05kg accuracy) will be used to weigh the subjects. A stadiometer (Holtain Ltd., UK) with 200 cm limit and ± 0.01 cm accuracy will be used to measure body height. The BMI will be calculated from the body weight and height.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Waist Circumference
Waist circumference will be measured on bare skin midway between the lowest rib and the superior border of the iliac crest using an inelastic measuring tape to the nearest 0.1 cm. Measurement will be performed at the end of normal expiration.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Hip Circumference
Hip circumference will be be taken on bare skin around the widest portion of the buttocks using an inelastic measuring tape to the nearest 0.1 cm and the tape should be placed parallel to the floor.
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Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
VO2max
VO2max test will be conducted using a calibrated motor-driven treadmill (LE500C, Jaeger, Germany) by continuous metabolic VO2 measurement using a Cosmed K5 portable telemetric gas analysis system. The test will be performed using a ramp protocol where the speed will be constant and the incline will be increased by 2% every second minute until VO2max is reached. Capillary blood will be obtained before and immediately after the test for the blood lactate analysis. The highest value of VO2 which meets one of the following criteria will be considered as the VO2max: 1) plateau of VO2 with increasing intensity, 2) respiratory exchange ratio (RER) ≥1.05, and 3) post-exercise blood lactate exceeding 8 mmol/L.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Blood Pressure
Subjects will abstain from consuming caffeine and alcohol at least 10 hours prior to the assessment. After 10 minutes rest in the seated position, blood pressure will be measured on the right arm using a blood pressure monitor (M3 Vital Signs Monitor, EDAN). Systolic and diastolic blood pressure and mean arterial pressure will be obtained over the brachial artery region with the arm supported at the heart level using an appropriately sized cuff. Measurements will be repeated after 10 minutes and the average of two separate measurements will be recorded for the analysis.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Lean Mass
Total body lean mass will be determined by using DXA scan.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Bone Mineral Density
Bone mineral density will be determined by using DXA scan.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Fasting glucose
Subjects will fast overnight for 10 hours. Subjects will sit in a quiet environment for 15 minutes prior to blood collection. Venous blood will be drawn from an antecubital vein in the forearm by a certified phlebotomist and sent to an accredited medical laboratory to measure the level of fasting glucose.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Insulin
Subjects will fast overnight for 10 hours. Subjects will sit in a quiet environment for 15 minutes prior to blood collection. Venous blood will be drawn from an antecubital vein in the forearm by a certified phlebotomist and sent to an accredited medical laboratory to measure the level of insulin.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
HbA1c
Subjects will fast overnight for 10 hours. Subjects will sit in a quiet environment for 15 minutes prior to blood collection. Venous blood will be drawn from an antecubital vein in the forearm by a certified phlebotomist and sent to an accredited medical laboratory to measure the level of HbA1c.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Alanine aminotransferase ALT
Subjects will fast overnight for 10 hours. Subjects will sit in a quiet environment for 15 minutes prior to blood collection. Venous blood will be drawn from an antecubital vein in the forearm by a certified phlebotomist and sent to an accredited medical laboratory to measure the level of ALT.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Aspartate aminotransferase AST
Subjects will fast overnight for 10 hours. Subjects will sit in a quiet environment for 15 minutes prior to blood collection. Venous blood will be drawn from an antecubital vein in the forearm by a certified phlebotomist and sent to an accredited medical laboratory to measure the level of AST.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
LDL cholesterol
Subjects will fast overnight for 10 hours. Subjects will sit in a quiet environment for 15 minutes prior to blood collection. Venous blood will be drawn from an antecubital vein in the forearm by a certified phlebotomist and sent to an accredited medical laboratory to measure the level of LDL cholesterol.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
HDL cholesterol
Subjects will fast overnight for 10 hours. Subjects will sit in a quiet environment for 15 minutes prior to blood collection. Venous blood will be drawn from an antecubital vein in the forearm by a certified phlebotomist and sent to an accredited medical laboratory to measure the level of HDL cholesterol.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up.
Total cholesterol
Subjects will fast overnight for 10 hours. Subjects will sit in a quiet environment for 15 minutes prior to blood collection. Venous blood will be drawn from an antecubital vein in the forearm by a certified phlebotomist and sent to an accredited medical laboratory to measure the level of total cholesterol.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up.
Triglycerides
Subjects will fast overnight for 10 hours. Subjects will sit in a quiet environment for 15 minutes prior to blood collection. Venous blood will be drawn from an antecubital vein in the forearm by a certified phlebotomist and sent to an accredited medical laboratory to measure the level of triglycerides.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up.
Class adherence
Class attendance will be recorded to indicate adherence to HIIT intervention. Subjects will be encouraged to achieve \>70% class attendance over the year.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Dropout rate
The reasons for dropout will be ascertained and reported.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Dose-response relationship between attendance and other outcome variables
Secondary analysis will be performed based on the attendance rate to examine the dose-response relationship between HIIT and the other outcome variables.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Quality of Life measured by Short Form-12
The validated Chinese version Standard SF-12 Health Survey will be used to measure health-related quality of life. This 12-item questionnaire assesses physical functioning, emotional and mental health, bodily pain, general health, vitality and social functioning. A higher overall score indicates better quality of life.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Mental Health measured by the Hospital Anxiety and Depression Scale (HADS)
The Hospital Anxiety and Depression Scale (HADS) will also be used to evaluate the severity of depression and anxiety. This 7-item questionnaire has an overall score ranging from 0 to 21 (with subscales for both anxiety and depression). A higher score indicates more severe symptoms.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Anxiety level measured by Generalized Anxiety Disorder-7 (GAD-7)
Generalized Anxiety Disorder-7 (GAD-7) will also be used to measure the anxiety level of the subjects. This 7-item questionnaire has an overall score ranging from 0 to 21. A higher score indicates more severe symptoms.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Depression level measured by Patient Health Questionnaire-9 (PHQ-9)
Patient Health Questionnaire-9 (PHQ-9) will also be used to measure the depression level of the subjects. This 10-item questionnaire has an overall score ranging from 0 to 30. A higher score indicates more severe symptoms.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Sleep Quality
Pittsburgh Sleep Quality Index (PSQI) will be used to measure the subjective sleep quality of the subjects. The score of this scale ranges from 0 to 21. Higher score indicates worse subjective sleep quality.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Adverse Events
Adverse events will be closely monitored through regular surveys by the athletics coaches and research personnel, and by voluntary reports from the subjects. The incidence rate in both usual care control group and HIIT group will be calculated as incidence rate = number of adverse events in each group / number of participants in each group.
Time frame: The adverse events will be recorded during the one-year intervention period
Medication usage
The number of participants in each group using dyslipidemic and hypertensive medications will be recorded, including e.g., drug name, type, dose and weekly frequency).
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Habitual Physical Activity
Habitual physical activity will be measured by International Physical Activity Questionnaire (IPAQ) and 7-day actigraph. Subjects will wear the actigraph at the hip region for 24 hours over 8 consecutive days. The first day will be a trial and not be included into the analysis.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up
Dietary Intake
The dietary intake will be measured by 3-day weighed food record and analyzed by Food Processor, ESHA. A food ingestion report will be generated by the software, including total calories intake, proportion of major macro nutrients.
Time frame: All assessments will be repeated at 12 months post-intervention and at 24 months at the follow-up