Hybrid Exercise Training for Health, Performance and Well-Being (DoIT II)

Study Overview
=================
Brief Summary
-----------------
Observing a lack of research investigating the chronic physiological and psychological responses to this type of exercise training the aim of this study is to investigate the optimal training configurations of DoIT to produce positive effects on health, performance and quality of life markers in sedentary overweight or obese adults aged 30-55 years. The DoIT program will be performed in a small-group setting indoor or outdoor implementing a progressive manner for 12 months and using bodyweight exercises with alternative modes.

Detailed Description
-----------------
This controlled, randomized, four-group, repeated-measures clinical trial will be consisted of the following stages: Initial testing: body weight and height, RMR, daily physical activity (PA), daily nutritional intake. a 4-week adaptive period: based on a dietary analysis, participants will be given a dietary plan (considering the RMR and total daily physical activity related energy expenditure), providing an isocaloric diet over the initial 4-week adaptive period. During this adaptive period, volunteers will also be familiarized with exercises techniques and overload patterns that will be used throughout the study through 4 preparatory sessions. At the end of the adaptation period, participants will participate in assessment procedures (baseline testing) at University facilities. After the adaptive period all participants will be randomly assigned to four groups (control, 1 session/week, 2 sessions/week, 3 sessions/week). The exercise protocols that will be used throughout the 1-year intervention will be consisted of 8-12 neuromotor exercises in circuit fashion applying prescribed time (15-45 sec) of effort and passive recovery intervals. After 12 months of exercise intervention all participants will participate in assessment procedures (post-training testing) at University facilities within 5 days after the completion of the last training session. All participants will be randomly assigned to the following four groups: Control group (no training) DoIT-1 (1 session/week) DoIT-2 (2 sessions/week) DoIT-3 (3 sessions/week)

Official Title
-----------------
The Dose-response Effect of High-intensity Interval Neuromuscular Training on Health, Performance and Quality of Life in Overweight/Obese Adults: The DoIT Trial

Conditions
-----------------
High-Intensity Interval Training, Body Composition, Performance, Habitual Physical Activity

Intervention / Treatment
-----------------
* Behavioral: DoIT-1
* Behavioral: DoIT-2
* Behavioral: DoIT-3
* Behavioral: Control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: inactivity (no exercise participation for ≥6 months before the study; VO2max <30 ml·kg-1·min-1) age of 30-55 years overweight/obese (BMI 25.0-39.9) body fat percentage for women > 32% and for men > 25% waist circumference for women > 80 cm and for men > 94 cm medical clearance for strenuous physical training no smoking for ≥6 months before the study no diet intervention or usage of nutritional supplements/medications before (≥6 months) and during the study no weight loss greater >10% of body mass before (≤6 months) the study no diagnosis or symptoms of cardiovascular, metabolic, pulmonary, renal, musculoskeletal or mental disorders Exclusion Criteria: Participants will be excluded from the study if they: will not participate in ≥80% of total exercise sessions will adhere to a nutritional intervention during the study will modify the habitual physical activity levels during the study

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control<br>No intervention. Participated only in measurements at baseline, at 6 months and at 12 months. | Behavioral: Control<br>* No training will be performed during a 1-year period. Participation only in measurements.<br>|
| Experimental: DoIT-1<br>Participated in a supervised 1-year workout exercise training program once per week and in measurements at baseline, at 6 months and at 12 months. | Behavioral: DoIT-1<br>* A hybrid small-group (5-10 participants/session) training modality, that combines interval training, circuit-based resistance exercise and functional training and performed according to a periodized model of exercise prescription as an alternative approach for weight management, health, performance and well-being. DoIT will be performed once per week on non-consecutive days for 12 months.<br>* Other names: Hybrid Interval Training;|
| Experimental: DoIT-2<br>Participated in a supervised 1-year workout exercise training program twice per week and in measurements at baseline, at 6 months and at 12 months. | Behavioral: DoIT-2<br>* A hybrid small-group (5-10 participants/session) training modality, that combines interval training, circuit-based resistance exercise and functional training and performed according to a periodized model of exercise prescription as an alternative approach for weight management, health, performance and well-being. DoIT will be performed twice per week on non-consecutive days for 12 months.<br>* Other names: Hybrid Interval Training;|
| Experimental: DoIT-3<br>Participated in a supervised 1-year workout exercise training program thrice per week and in measurements at baseline, at 6 months and at 12 months. | Behavioral: DoIT-3<br>* A hybrid small-group (5-10 participants/session) training modality, that combines interval training, circuit-based resistance exercise and functional training and performed according to a periodized model of exercise prescription as an alternative approach for weight management, health, performance and well-being. DoIT will be performed thrice per week on non-consecutive days for 12 months.<br>* Other names: Hybrid Interval Training;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body mass | Body mass (kg) will be measured using a beam scale | At baseline, at 6 months and at 12 months | 
| Change in body mass index | Body mass index will be calculated using the Quetelet's equation | At baseline, at 6 months and at 12 months | 
| Change in waist circumference | Waist circumference (cm) will be measured using a Gullick II tape | At baseline, at 6 months and at 12 months | 
| Change in hip circumference | Hip circumference (cm) will be measured using a Gullick II tape | At baseline, at 6 months and at 12 months | 
| Change in waist-to-hip ratio | Waist-to-hip ratio will be calculated by dividing the waist by the hip measurement | At baseline, at 6 months and at 12 months | 
| Change in body fat | Body fat (%) will be assessed by whole-body dual-energy X-ray absorptiometry (DXA) | At baseline and at 12 months | 
| Change in fat mass | Body fat (kg) will be assessed by whole-body dual-energy X-ray absorptiometry (DXA) | At baseline and at 12 months | 
| Change in fat-free mass | Fat-free mass (kg) will be assessed by whole-body dual-energy X-ray absorptiometry (DXA) | At baseline and at 12 months | 
| Change in resting metabolic rate (RMR) | RMR (kcal) will be measured using a portable open-circuit indirect calorimeter with a ventilated hood system | At baseline, at 6 months and at 12 months | 
| Change in maximal strength (1RM) | 1RM (kg) for the lower body will be measured bilaterally on a horizontal leg press, seated leg extension and lying leg curl machines while 1RM (kg) for the upper body will be measured on a seated chest press and lat pull-down machines | At baseline, at 6 months and at 12 months | 
| Change in maximal oxygen consumption (VO2max) | VO2max (ml/kg/min) will be estimated using a low-risk, low-cost and single-stage submaximal treadmill walking test | At baseline, at 6 months and at 12 months | 
| Change in habitual physical activity (PA) | Seven-day habitual PA (MET-min/week) will be assessed using the International Physical Activity Questionnaire (IPAQ) | At baseline, at 3, 6, 9 and 12 months | 
| Change in dietary intake | Dietary intake (kcal) will be assessed using 7-day diet recalls | At baseline, at 3, 6, 9 and 12 months | 
| Change in body mass content (BMC) | BMC (g) will be assessed by dual-energy X-ray absorptiometry (DXA) of the total body and non-dominant hip. | At baseline and at 12 months | 
| Change in body mass density (BMD) | BMD (g) will be assessed by dual-energy X-ray absorptiometry (DXA) of the total body and non-dominant hip. | At baseline and at 12 months | 
| Change in resting systolic (SBP) and diastolic (DBP) blood pressures. | Resting SBP (mmHg) and DBP (mmHg) will be assessed by a manual sphygmomanometer | At baseline, at 6 months and at 12 months | 
| Change in mean arterial pressure (MAP). | MAP (mmHg) will be calculated using the following equation: MAP = SBP + (DBP × DBP) / 3 | At baseline, at 6 months and at 12 months | 
| Change in resting heart rate (RHR). | RHR (bpm) will be measured by pulse palpation for 60 seconds. | At baseline, at 6 months and at 12 months | 
| Change in muscular endurance | Muscular endurance (repetitions until muscle failure) will be assessed using timed tests (60 sec) for the abdominal musculature, upper and lower body. The tests will include partial curl-up, push-up for males and modified push-up for females (kneeling position) and modified chair squat, respectively | At baseline, at 6 months and at 12 months | 
| Change in flexibility | Flexibility (cm) will be assessed using the modified sit-and-reach test | At baseline, at 6 months and at 12 months | 
| Change in static balance | Static balance (sec) will be assessed using the Sharpened Romberg test | At baseline, at 6 months and at 12 months | 
| Change in functional capacity | Functional capacity will be assessed using a movement-based screening tool titled Functional Movement Screening (FMS). The FMS will be consisted of 7 movement tasks that will be scored from 0 to 3 points and the sum will create score ranging from 0 to 21 points (0 = pain with pattern regardless of quality, 1 = unable to perform pattern, 2 = able to perform pattern with compensation/imperfection, 3 = able to perform pattern as directed). | At baseline, at 6 months and at 12 months | 
| Change in blood lipids | Total serum cholesterol (mmol/L), triglycerides (mmol/L), low-density lipoprotein (mmol/L) and high-density lipoprotein (mmol/L) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in blood inflammatory markers | Cytokines, lipocalines, CRP, oxidative stress markers will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in cortisol | Cortisol (nmol/L) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in insulin | Insulin (mIU/L) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in homeostatic model assessment for insulin resistance (HOMA-IR) | HOMA-IR will be measured with commercially availlable kits. ΗΟΜΑ score will be calculated using the equation HOMA-IR = fasting insulin (mIU/L) x fasting glucose (mg/dL) / 405. HOMA-IR score will be classified using the following range: normal insulin resistance < 3, moderate insulin resistance 3-5, severe insulin resistance > 5) | At baseline and at 12 months | 
| Change in leptin | Leptin (μg/L) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in adiponectin | Adiponectin (μg/mL) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in interleukin 1 beta (IL-1b) and interleuking 6 (IL-6) | IL-1b and IL-6 (pg/ml) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in fasting blood glucose (FBG) | FBG (mg/dL) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in serum protein carbonyl levels | Protein carbonyl (mg) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in thiobarbituric acid-reactive substances (TBARS) | TBARS (nmol/mg protein) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in reduced (GSH) and oxidized (GSSG) glutathione | GSH and GSSG (nmol/L) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in catalase activity | Catalase activity (units) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in total antioxidant capacity (TAC) | TAC (mmol/l) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in C-reactive protein (CRP) | CRP (mg/L) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in cholecystokinin (CKK) | CKK (ng/ml) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in pancreatic polypeptide (PP) | PP (pg/ml) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in peptide YY (PYY) | PYY (ng/ml) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in oxyntomodulin (OXM) | OXM (pg/ml) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in ghrelin | Ghrelin (pg/ml) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in glucagon-like peptide-1 (GLP-1) | GLP-1 (pg/ml) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in appetite | The Visual Analog Scale (VAS) will be used to measure perceived hunger, satiety, and individual's own interpretation of their hunger sensations. VAS is a straight horizontal line of fixed length, usually 100 mm. The ends are defined as the extreme limits of the parameter to be measured orientated from the left (worst) to the right (best). | At baseline, at 6 months and at 12 months | 
| Change in quality of life | Quality of life will be assessed using the physical and mental component subscales of the Greek 36-Item Short-Form Health Survey (SF-36). The scores on both component subscales of the SF-36 will range from 0 to 100, with higher scores indicating better health status while the minimal clinically important difference will be 2 points. | At baseline, at 6 months and at 12 months | 
| Change in exercise enjoyment | Exercise enjoyment will be assessed using the Exercise Enjoyment Scale (EES), which is a single-item 7-point scale to assess enjoyment pre-, during, and post-exercise ranging from not at all at 1 to extremely at 7. | At baseline, at 6 months and at 12 months | 
| Change in affective valence | Affective responses to exercise will be assessed using the Feeling Scale (FS), which is a single-item 11-point scale to assess feeling of pleasure pre-, during, and post-exercise training ranging from very good at -5 to very bad at 5. | At baseline, at 6 months and at 12 months | 
| Change in irisin | Irisin (ng/ml) will be measured with commercially availlable kits | At baseline and at 12 months | 
| Change in left ventricular end-diastolic volume (LVEDV). | LVEDV (ml) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in left ventricular end-systolic volume (LVESV). | LVESV (ml) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in left ventricular stroke volume (LVSV). | LVSV (ml) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in interventricular septum end diastole (IVSd). | IVSd (mm) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in interventricular septum end diastole (IVSs). | IVSs (mm) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in left ventricular ejection fraction (LVEF). | LVEF (%) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in left ventricular internal diameter end diastole (LVIDd). | LVIDd (mm) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in left ventricular internal diameter end systole (LVIDs). | LVIDs (mm) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in left ventricular posterior wall end diastole (LVPWd). | LVPWd (mm) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in left ventricular mass (LV mass). | LV mass (g) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in left atrial (LA) diameter. | LA diameter (mm) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in aortic root. | Aortic root (mm) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in aortic valve velocity (AoV Vel). | AoV Vel (cm/s) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in aortic valve pressure gradient (AoV PG). | AoV PG (mmHg) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in right ventricular end diastole (RVD). | RVD (mm) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in pulmonary artery systolic pressure (PASP). | PASP (mmHg) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in left ventricular fractional shortening (FS). | Fractional shortening (%) will be measured using echocardiography. | At baseline and at 12 months | 
| Change in depression II. | Depression will be measured using the Patient Health Questionnaire (PHQ-9)), which is a self-administered instrument consisiting of 9 multiple-choice questions scored from 0 to 3. Higher total scores indicate higher depression severity. | At baseline, at 6 months and at 12 months | 
| Change in depression I. | Depression will be measured using the Beck Depression Inventory (BDI), which is a self-report questionnaire consisiting of 21 multiple-choice questions scored from 0 to 3. Higher total scores indicate more severe depressive symptoms. | At baseline, at 6 months and at 12 months | 
| Change in depression and anxiety. | Both depression and anxiety will be measured using the Hospital Anxiety and Depression Scale (HADS), which is a 14-item scale that generates ordinal data. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. Higher scores indicate greater anxiety and depression. | At baseline, at 6 months and at 12 months | 
| Change in mood. | Mood will be measured using the Profile of Mood States (POMS) questionnaire, which uses a unipolar scale to rate the extent to which they are experiencing or have experienced 20 affect states in the past week using a 5-point scale (0 = not at all, 4 = extremely). Higher scores indicate greater negative mood. | At baseline, at 6 months and at 12 months | 
| Change in anxiety. | Anxiety will be measured using the State-Trait Anxiety Inventory (STAI), which is an instrument that has 20 items for assessing trait anxiety and 20 for state anxiety. All items are rated on a 4-point scale (e.g., from Almost Never to Almost Always). Higher scores indicate greater anxiety. | At baseline, at 6 months and at 12 months | 
| Change in physical self. | Physical self will be measured using the Physical Self-Perception Profile (PSPP), which is an instrument with 30 questions comprising five 6-item subscales. Each item has a four-point structured-alternative format. Scores range from 6 to 24 on each subscale, with high scores representing positive perceptions. Half of the items are worded in the negative direction. | At baseline, at 6 months and at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in exercise-induced caloric expenditure | Measured using a portable indirect calorimetry system | At baseline, at 6 months and at 12 months | 
| Change in blood lactate concentration (BLa) | BLa (mmol/L) concentration will be measured in a microphotometer with commercially available kits. Blood samples will be collected pre-, mid- and post-exercise session (single bout) at 3 min post-exercise | At baseline, at 6 months and at 12 months | 
| Change in peak expiratory flow (PEF) | PEF (l/s) will be measured using the maximum flow volume loop. | At baseline and at 12 months | 
| Change in forced expiratory flow between 25 and 75% of vital capacity (FEF25-75). | FEF25-75 (l/s) will be measured using the maximum flow volume loop. | At baseline and at 12 months | 
| Change in forced expiratory volume at 1 s (FEV1). | FEV1 (l) will be measured using the maximum flow volume loop. | At baseline and at 12 months | 
| Change in forced vital capacity (FVC). | FVC (l) will be measured using the maximum flow volume loop. | At baseline and at 12 months | 
| Change in the ratio of FEV1/FVC. | FEV1/FVC (%) will be measured using the maximum flow volume loop. | At baseline and at 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
neuromuscular training, functional training, circuit training, interval training