Exercise and Genes in Obese (EGO)

Study Overview
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Brief Summary
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Regular exercise has several positive health effects including increased physical fitness and muscle mass. It is well known that increased muscle mass is associated with increased resting energy expenditure which may facilitate weight loss and maintenance. Previous studies have, however, failed to show any consistent association between the intensity of physical exercise and energy expenditure, or relate the variance in these adaptations to genetic variability. Whether high-intensity exercise (HIE) is associated with improved health related quality of life in severely obese patients remains unknown. This PhD-project is based on a planned randomised controlled study including 50 or more treatment seeking morbidly obese patients who will be randomised to either a 24 week moderate-intensity exercise (MIE) programme or a 24 week high-intensity exercise (HIE) programme. The investigators main hypothesis is that patients randomised to the HIE-program will achieve higher energy expenditure during rest and physical activity after treatment than those allocated to the MIE-programme. In addition, the investigators hypothesise that the HIE-group will achieve a better health related quality of life than the MIE-group after treatment. The investigators also hypothesize that inter-individual variability in adaptation to the two training regimens may be due to genetic factors. If the investigators hypotheses are confirmed, this project might have beneficial clinical implications for future obesity treatment strategies.

Official Title
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The Effect of Exercise and Genes on Energy Expenditure, Appetite and Quality of Life in Morbidly Obese Patients

Conditions
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Obesity

Intervention / Treatment
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* Other: Training intensity intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment seeking weight stable morbidly obese patients (BMI ≥ 40 kg/m2 or BMI 35 to 39.9 kg/m2 with ≥ 1 co morbidity) attending the outpatient Obesity Center, Vestfold Hospital Trust, will be informed about this RCT . Exclusion Criteria: Uncompensated heart failure Recent myocardial infarction or stroke (<½ years) Severe arrhythmia or heart failure Unstable angina pectoris Renal failure Pregnancy Severe eating disorders Active substance abuse Being on a diet Taking medication known to affect appetite or metabolism (including thyroxin).
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: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High intensity training group<br>HIE will consist of the following: 10 minute warm up at 70% of maximal heart rate. 4 minute exercise intervals at 90-95% of maximal heart rate. 4 minute interval bouts repeated 4 times. Between each bouts there will be a 3 minute active recovery at 70% of maximal heart rate After all four bouts are completed; 5 minute cool-down at 70% of maximal heart rate. | Other: Training intensity intervention<br>* High intensity training group describes the group performing high intensity exercise intervention. Moderate intensity training group describes the the group performing moderate exercise intervention<br>* Other names: EGO-HIT;|
| Experimental: Moderate intensity training group<br>MIE will consist of the following: 10 minute warm up at 50% of maximal heart rate. 35 minutes exercise at 70% of maximal heart rate. 4 minute cool-down at 50% of maximal heart rate. | Other: Training intensity intervention<br>* High intensity training group describes the group performing high intensity exercise intervention. Moderate intensity training group describes the the group performing moderate exercise intervention<br>* Other names: EGO-HIT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Energy expenditure during physical activity | Energy expenditure (EE) during volitional activity will be measured with ergo-spirometry tests one week before the exercise intervention period starts, and repeated after each exercise period. Increasing the aerobic work capacity is supposed to give the same proportional increase in energy expenditure at any given maximal intensity. | 0, 8, 12 and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting metabolic rate | Resting metabolic rate will be measured with ergo-spirometry test one week before the exercise intervention period starts, and repeated after each exercise period. Increasing the aerobic work capacity is supposed to give increased resting metabolic rate. | 0, 8, 12 and 24 weeks | 
| Cardiorespiratory fitness | Exercise may have a positive effect on cardiorespiratory fitness and will be measured with ergo-spirometry test | 0, 8, 12 and 24 weeks | 
| Body mass index | Exercise may have a positive effect on weight change and will be calculated as weight in kilograms divided by height in meters squared | 0, 8, 12 and 24 weeks | 
| Waist circumference | Exercise may have a positive effect on waist circumference and will be measured midway between the bottom edge of the lower rib and upper iliac crest in the horizontal plane. | 0, 8, 12 and 24 weeks | 
| Fat mass and fat free mass | Exercise may have a positive effect on body composition and will be measured with the bioelectrical impedance analyser Tanita BC-418 | 0, 8, 12 and 24 weeks | 
| Appetite control | Patient self-appraisal of hunger and fullness will be assessed during fasting and after a standardised breakfast every 30 minutes (for a period of 3hours) using visual analogue scales. | 0,12 and 24 weeks | 
| Genetic susceptibility | We hypothesize that inter-individual variability in adaptation/response to the two training regimens may also be due to genetic factors. We have designed a gene panel consisting of recognized and previously reported risk genes/variants with flanking sequences relevant for exercise (VO2max), participation in physical activity, obesity, diabetes, asthma and obesity related sub-phenotypes. The panel covers 1.2 Mb and includes 299 genes (exons with exon-intron junctions) and 1468 intronic and intergenic SNPs. Next-generation sequencing will be performed using a gene panel of selected genes/genetic regions by Illumina Nextera technology. The method involves enzymatic fragmentation of DNA and probe-based enrichment. The samples will be sequenced (paired-end, 2x100 bp) on a HiScanSQ. All wet lab methods (with other gene panels) are ISO15189 certified and in routine use at Unit for Medical Genetics at Telemark Hospital. | 0, 8, 12 and 24 weeks | 
| Short form health survey (RAND-36) | RAND-36 is a 36-item measure of generic HRQOL consisting of eight additive subscales (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health) and two summary scores each based on four subscales (Physical Component Summary and Mental Component Summary). Scores on all subscales range from 0 to 100. Summary-scores will be norm-based, with mean (SD) 50 (10). Higher scores on all scales represent better HRQOL. | 0,12 and 24 weeks | 
| Impact on Weight Questionnaire (IWQOL-Lite) | IWQOL-Lite is a 36-item measure of generic HRQOL consisting of eight additive subscales (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health) and two summary scores each based on four subscales (Physical Component Summary and Mental Component Summary). Scores on all subscales range from 0 to 100. Summary-scores will be norm-based, with mean (SD) 50 (10). Higher scores on all scales represent better HRQOL. | 0,12 and 24 weeks | 
| Weight-Related Symptom Measure (WRSM) | WRSM is a 20-item measure for the presence and distress of 20 weight-related symptoms. The distress scores of the symptoms are reported on a six-point likert scale. Two summary scores are calculated; an additive score of presence of symptoms ranging from 1 to 20 and a symptom distress score for all symptoms. Symptom distress scores range from 0 to 100, with higher scores indicating a higher or worse total symptom distress. | 0,12 and 24 weeks | 
| Power of Food scale (PFS) | PFS assess both the psychological impact and respondent's responsiveness to a food-abundant environment. This is a 15-item scale whose items pertain to three situations: food being readily available in the environment but not physically present, food is physically present, but not tasted, and food is first tasted but not already consumed. The three subscales is scored 0-100 with higher scores indicating greater eating problems. | 0,12 and 24 weeks | 
| Binge Eating Scale (BES) | BES comprise 16 items assessing binge eating problems. Additive scores range between 0-46, with higher scores indicating greater problems. Cut-off scores have been established to determine binge severity, with severe represented by scores > 27, moderate by scores 18-26, and mild-none by scores < 17. | 0,12 and 24 weeks | 
| Three Factor Eating Questionnaire (TFEQ -R21) | TFEQ -R21 is a 21-item questionnaire covering eating behavior domains: the cognitive restraint scale (6 items) assesses control over food intake and influence over body weight and body shape; the emotional eating scale (6 items) measures the propensity to overeat in relation to negative mood states, e.g., when feeling lonely, anxious, or depressed; and, the uncontrolled eating scale (9 items) assesses the tendency to lose control over eating when feeling hungry or when exposed to external stimuli | 0,12 and 24 weeks | 
| Body weight change | Exercise may have a positive effect on weight change | 0, 8, 12 and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise and Genes in Obese (EGO)