Cardiovascular DiseasesNCT05895916
Extreme Exercise and Energy Expenditure (4E) Study
A study testing High-volume road cycling in people with Cardiovascular Diseases and Obesity, Visceral, run by Institut universitaire de cardiologie et de pneumologie de Québec, University Laval at 1 site in Canada.
Trial summary
The goal of this clinical trial is to provide evidence, through an extreme exercise prescription (1,144 km of road cycling on seven consecutive days), that weight loss is not the appropriate outcome to evaluate the effects of exercise on abdominal adiposity and ectopic fat depots (e.g. Read more about this study
- Who is it for?
- Ages 50 to 66 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases, Obesity, Visceral, Liver Fat
- What is being tested?
- High-volume road cycling
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteCanada
- Study dates
- 7 Jun 2018to 13 Aug 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 66 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male
- Between the ages of 50 and 66 years
- Asymptomatic for cardiovascular disease
- Reporting at least 5,000 km per year of road cycling at an average pace of about 30 km/h
Who cannot join
- Retired competitive athletes/competitive athletes
- Undergoing hormonal or corticosteroid therapy
- Presenting a cancer not in remission
- Presenting an absolute contraindication to MRI
- Presenting an absolute contraindication to maximal cardiopulmonary exercise testing
Trial locations and contacts
1 site in 1 country.
Canada1 site
Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
Québec, G1V 4G5
About this study
The goal of this clinical trial is to provide evidence, through an extreme exercise prescription (1,144 km of road cycling on seven consecutive days), that weight loss is not the appropriate outcome to evaluate the effects of exercise on abdominal adiposity and ectopic fat depots (e.g. liver fat and epi/pericardial fat) in eleven recreational middle-aged male cyclists (aged 50 to 66 years) without symptoms of cardiovascular disease. The main questions it aims to answer are:
- If energy intake is substantially increased to compensate energy expenditure and prevent weight loss following an extreme exercise prescription, will significant changes in body composition and body fat distribution be observed?
- Will these changes translate into improvements in the cardiometabolic health profile even in the absence of weight loss?
Participants will be asked to partake in several evaluations: fasting plasma lipoprotein-lipid profile and inflammation markers, glycated hemoglobin, cardiorespiratory fitness, submaximal exercise test including measurement of energy expenditure, resting and exercise blood pressure and heart rate, evaluation of regional adiposity, liver fat content, epi/pericardial fat, nutritional quality, and level of physical activity. After baseline evaluations, participants will be asked to alternately bike 208 km and 104 km per day on a pre-specified course for seven consecutive days. They will be accompanied during each of the seven bike rides by research professionals in a recreational vehicle. Participants' weight, body composition and waist circumference will be measured under standardized conditions in the morning after an overnight fast and after the exercise. Their heart rate will be continuously monitored, and participants will wear accelerometers to estimate their daily exercise-related energy expenditure. Foods and fluids will be provided to participants and recorded. At the end of the 1,144 km/ 7-days bike ride, baseline evaluations will be repeated with the exception of the maximal exercise treadmill test, nutritional quality, and level of physical activity. To facilitate the conduct of the protocol, the eleven participants will be evaluated and followed in two distinct groups.
Read the detailed description
Although there is robust evidence that a physically active lifestyle including regular leisure time physical activity and exercise (>150 min per week of moderate to vigorous exercise per week) is associated with a reduced mortality risk and improved cardiometabolic health, some scientists have promoted the notion (which has certainly been taken up by the lay press) that if one wants to lose weight, focus should be placed on caloric restriction rather than on exercise. Several academic debates have been held on this issue which have left some health professionals and the public confused and perplexed.
The investigators' research group has been active in this area on several fronts. First, the investigators have pioneered the notion that in cardiovascular and "metabolic" medicine, the health risk of overweight and obesity was not appropriately assessed by an index based on body weight (body mass index, which is expressed in kg/m^2). For instance, using imaging technology (computed tomography), the investigators were among the first, more than 30 years ago, to begin to extensively study regional body fat distribution, showing that excess visceral adipose tissue accumulation was more closely related to an atherogenic and diabetogenic cardiometabolic risk profile than excess body weight or total body fat. As sedentary individuals with a diet of poor nutritional value (rich in processed fat and added sugar - promoting preferential visceral fat deposition) are also often characterized by a lower muscle mass and by high levels of abdominal visceral fat, several lifestyle intervention studies that the investigators and others have conducted in sedentary males with visceral obesity have shown that with regular exercise, one could lose visceral adipose tissue while gaining muscle mass, which would lead to trivial or sometimes no changes in body weight. Thus, if body composition is altered by an energy deficit produced by regular exercise, the investigators have proposed that weight loss may sometime be misleading as an outcome as it may not always reflect favorable changes in body composition (muscle mass increasing) and in visceral adiposity and levels of ectopic fat (decreasing). On that basis, the investigators have proposed that changes in waist circumference could be more useful than body weight loss in the evaluation of the benefits of a lifestyle modification program involving regular endurance exercise such as brisk walking, jogging, or biking. For instance, the investigators have previously reported that waist circumference was rather sensitive to lifestyle changes involving regular physical activity/exercise. Accordingly, lifestyle intervention studies have shown that a reduction of 4 cm in waist girth was predictive of a 58% reduction in the risk of developing type 2 diabetes among individuals who were initially characterized by abdominal obesity and glucose intolerance.
Thus, there is a need to propose a paradigm shift among health professionals to evaluate the impact of lifestyle intervention programs involving physical activity/exercise in high-risk overweight obese individuals with visceral obesity: Weight loss is no longer the optimal or most clinically relevant outcome - losses of visceral adiposity and ectopic fat may be more relevant clinically.
In 2015, a member of the investigators' team was asked to write an editorial on a spectacular study which provided very relevant data to the debate about diet vs. exercise and weight loss. In that impressive exercise study, recreational middle-aged cyclists were required to bike 2,700 km over 14 days and asked to try to match their energy intake to their very large energy expenditure, the objective being not to lose weight over the course of the intervention. Thus, the daily exercise "prescription" was huge as the authors wanted to test the ability of these elderly and fit recreational cyclists to match their energy intake to their energy expenditure. The most striking and important finding of this unusual study is that despite the huge energy expenditure associated with the 2,700 km bike expedition, participants did not lose weight. However, such lack of change in body weight was completely misleading in terms of energy balance and changes in body composition. Indeed, the cyclists lost 2.2 kg of body fat while gaining 2.5 kg of fat-free mass, a remarkable finding considering that such changes were observed over a period of only two weeks.
Results of this study provide additional evidence that body weight is a poor outcome to assess the effect of a physical activity/exercise program. In the investigators' previously published exercise training studies, a common observation has been the disconnect between changes in body weight and changes in body composition, the latter being sometime observed even in the absence of weight loss. As weight poorly tracks changes in body composition induced by exercise, no wonder why exercise is indeed perceived as not being helpful to lose weight by some health professionals. The investigators propose that body weight is a misleading outcome when comes the time to evaluate the clinical benefits of exercise in individuals with overweight/obese.
One remaining and clinically important issue remains to be addressed regarding the effects of a large volume of exercise not inducing weight loss: to what extent substantial changes in visceral/ectopic fat could have been observed had imaging data been available? In addition, it would have been interesting for the 2,700 km bike intervention study to report changes in waist circumference, this metric being more sensitive to regular exercise than body weight. In the investigators' previous intervention studies, it has been their experience to find participants losing quite a bit of visceral fat and dropping their waistline by several centimeters, while not losing any body weight.
Thus, on the basis of the above observations, the investigators put forward the hypotheses that:
- a very large volume of exercise (1,144 km of bicycle performed for 7 consecutive days) will induce major changes in body composition and in levels of visceral adipose tissue/ectopic fat in a sample of middle-aged recreational cyclists who will be asked to match their energy intake to their very large energy expenditure during the course of the one-week extreme exercise intervention. Thus, in a study where, by design, no weight loss is planned nor wanted, the investigators expect to see major changes in body composition (slight increase in muscle mass and substantial reductions in the size of visceral adipose tissue and ectopic fat depots);
- changes in levels of visceral adipose tissue and ectopic fat will be better reflected by changes in waist circumference - which should decrease in the absence of body weight loss.
The investigators recognize that this is an extreme exercise prescription that has little relevance to public health. However, results of this study will be very important in shedding light on the importance of shifting our attention from body weight loss to other, more clinically relevant fat depots. Thus, the purpose of the study is to provide evidence, through an extreme exercise prescription, that weight loss is not the appropriate outcome to evaluate the effects of exercise on visceral adiposity and ectopic fat depots (e.g. liver fat and epi/pericardial fat) which will likely be mobilized to a very significant extent in only one week.
- Being tested
- High-volume road cycling
- Keywords
- cardiac fat, cardiometabolic health, cardiorespiratory fitness, ectopic fat, energy balance, exercise, liver fat, obesity, physical activity, visceral adipose tissue
- Medical subject headings
- Cardiovascular Diseases, Obesity, Abdominal, Fatty Liver, Metabolic Syndrome, Motor Activity, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-volume road cyclingBehavioural
1,144 km of road cycling performed on seven consecutive days with an increase in energy intake to maintain a stable body weight
| Study group | Role | What they receive |
|---|---|---|
| Extreme exercise group | Experimental | 1,144 km of road cycling on seven consecutive days Receives: Behavioral: High-volume road cycling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes from baseline in body weight assessed by direct segmental multi-frequency bioimpedance analysis following the extreme exercise prescription
Changes in body weight in kilograms
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fat mass assessed by direct segmental multi-frequency bioimpedance analysis following the extreme exercise prescription
Changes in fat mass in kilograms
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fat-free mass assessed by direct segmental multi-frequency bioimpedance analysis following the extreme exercise prescription
Changes in fat-free mass in kilograms
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in body water assessed by direct segmental multi-frequency bioimpedance analysis following the extreme exercise prescription
Changes in body water in kilograms
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in waist circumference assessed using a standardized measuring tape following the extreme exercise prescription
Changes in waist circumference in centimeters
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in visceral adipose tissue assessed using magnetic resonance imaging following the extreme exercise prescription
Changes in visceral adipose tissue in milliliters
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in subcutaneous adipose tissue assessed using magnetic resonance imaging following the extreme exercise prescription
Changes in subcutaneous adipose tissue in milliliters
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in epicardial adipose tissue assessed using magnetic resonance imaging following the extreme exercise prescription
Changes in epicardial adipose tissue in milliliters
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in pericardial adipose tissue assessed using magnetic resonance imaging following the extreme exercise prescription
Changes in pericardial adipose tissue in milliliters
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in liver fat content assessed using magnetic resonance imaging with spectroscopy following the extreme exercise prescription
Changes in liver fat content in percentage
Measured: Before and the day (or next day) following the extreme exercise prescription
Secondary outcomes (14)
Changes from baseline in fasting total cholesterol following the extreme exercise prescription
Changes in fasting total cholesterol in millimoles per liter
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting LDL cholesterol following the extreme exercise prescription
Changes in fasting LDL cholesterol in millimoles per liter
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting HDL cholesterol following the extreme exercise prescription
Changes in fasting HDL cholesterol in millimoles per liter
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting plasma triglycerides following the extreme exercise prescription
Changes in fasting plasma triglycerides in millimoles per liter
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting glycated hemoglobin following the extreme exercise prescription
Changes in fasting glycated hemoglobin in percentage
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting apolipoprotein A1 following the extreme exercise prescription
Changes in fasting apolipoprotein A1 in grams per liter
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting apolipoprotein B following the extreme exercise prescription
Changes in fasting apolipoprotein B in grams per liter
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting adiponectin following the extreme exercise prescription
Changes in fasting adiponectin in micrograms per milliliter
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting leptin following the extreme exercise prescription
Changes in fasting leptin in nanograms per milliliter
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting C-reactive protein following the extreme exercise prescription
Changes in fasting C-reactive protein in milligrams per liter
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting interleukin-6 following the extreme exercise prescription
Changes in fasting interleukin-6 in picograms per milliliter
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting tumor necrosis factor alpha following the extreme exercise prescription
Changes in fasting tumor necrosis factor alpha in picograms per milliliter
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in resting systolic blood pressure following the extreme exercise prescription
Changes in resting systolic blood pressure in millimeters of mercury
Measured: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in resting diastolic blood pressure following the extreme exercise prescription
Changes in resting diastolic blood pressure in millimeters of mercury
Measured: Before and the day (or next day) following the extreme exercise prescription
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2023
- Study start7 Jun 2018
- Primary completion13 Aug 2019
- Study completion13 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Natalie Alméras, Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
- Investigators
- Natalie Alméras, Ph.D., Principal investigator, Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05895916
- Sponsor's protocol ID
- 4E study
- Status last verified
- May 2023
- First submitted
- 17 May 2023
- Last updated
- 9 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kraus WE, Bittner V, Appel L, Blair SN, Church T, Despres JP, Franklin BA, Miller TD, Pate RR, Taylor-Piliae RE, Vafiadis DK, Whitsel L; American Heart Association Physical Activity Committee of the Council on Lifestyle and Metabolic Health, Council on Clinical Cardiology, Council on Hypertension, and Council on Cardiovascular and Stroke Nursing. The National Physical Activity Plan: a call to action from the American Heart Association: a science advisory from the American Heart Association. Circulation. 2015 May 26;131(21):1932-40. doi: 10.1161/CIR.0000000000000203. Epub 2015 Apr 27. No abstract available.
PubMed 25918126Luke A, Cooper RS. Physical activity does not influence obesity risk: time to clarify the public health message. Int J Epidemiol. 2013 Dec;42(6):1831-6. doi: 10.1093/ije/dyt159. No abstract available.
PubMed 24415616Malhotra A, Noakes T, Phinney S. It is time to bust the myth of physical inactivity and obesity: you cannot outrun a bad diet. Br J Sports Med. 2015 Aug;49(15):967-8. doi: 10.1136/bjsports-2015-094911. Epub 2015 Apr 22. No abstract available.
PubMed 25904145Blair SN, Archer E, Hand GA. Commentary: Luke and Cooper are wrong: physical activity has a crucial role in weight management and determinants of obesity. Int J Epidemiol. 2013 Dec;42(6):1836-8. doi: 10.1093/ije/dyt160. No abstract available.
PubMed 24415617Blair SN. Physical inactivity and obesity is not a myth: Dr. Steven Blair comments on Dr. Aseem Malhotra's editorial. Br J Sports Med. 2015 Aug;49(15):968-9. doi: 10.1136/bjsports-2015-094989. Epub 2015 Jun 10. No abstract available.
PubMed 26062953Despres JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis. 1990 Jul-Aug;10(4):497-511. doi: 10.1161/01.atv.10.4.497.
PubMed 2196040Despres JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodes-Cabau J, Bertrand OF, Poirier P. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1039-49. doi: 10.1161/ATVBAHA.107.159228. Epub 2008 Mar 20.
PubMed 18356555Despres JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012 Sep 4;126(10):1301-13. doi: 10.1161/CIRCULATIONAHA.111.067264. No abstract available.
PubMed 22949540Borel AL, Nazare JA, Smith J, Almeras N, Tremblay A, Bergeron J, Poirier P, Despres JP. Visceral and not subcutaneous abdominal adiposity reduction drives the benefits of a 1-year lifestyle modification program. Obesity (Silver Spring). 2012 Jun;20(6):1223-33. doi: 10.1038/oby.2011.396. Epub 2012 Jan 19.
PubMed 22262155Ross R, Dagnone D, Jones PJ, Smith H, Paddags A, Hudson R, Janssen I. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Ann Intern Med. 2000 Jul 18;133(2):92-103. doi: 10.7326/0003-4819-133-2-200007180-00008.
PubMed 10896648Despres JP. Obesity and cardiovascular disease: weight loss is not the only target. Can J Cardiol. 2015 Feb;31(2):216-22. doi: 10.1016/j.cjca.2014.12.009. Epub 2014 Dec 11.
PubMed 25661557Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
PubMed 11832527Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. doi: 10.1056/NEJM200105033441801.
PubMed 11333990Despres JP. Exercise and energy balance: going to extremes to show that body weight is not the best outcome. Am J Clin Nutr. 2015 Dec;102(6):1303-4. doi: 10.3945/ajcn.115.124560. Epub 2015 Nov 11. No abstract available.
PubMed 26561630Rosenkilde M, Morville T, Andersen PR, Kjaer K, Rasmusen H, Holst JJ, Dela F, Westerterp K, Sjodin A, Helge JW. Inability to match energy intake with energy expenditure at sustained near-maximal rates of energy expenditure in older men during a 14-d cycling expedition. Am J Clin Nutr. 2015 Dec;102(6):1398-405. doi: 10.3945/ajcn.115.109918. Epub 2015 Oct 21.
PubMed 26490491
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extreme Exercise and Energy Expenditure (4E) Study
- ClinicalTrials.gov ID
- NCT05895916
- Acronym / sponsor ID
- 4E study
- Keywords
- cardiac fat, cardiometabolic health, cardiorespiratory fitness, ectopic fat, energy balance, exercise, liver fat, obesity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Institut universitaire de cardiologie et de pneumologie de Québec, University LavalUniversity, hospital or other
- Study start
- 7 Jun 2018 (actual)
- Primary completion
- 13 Aug 2019 (actual)
- Study completion
- 13 Aug 2019 (actual)
- First posted
- 9 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to provide evidence, through an extreme exercise prescription (1,144 km of road cycling on seven consecutive days), that weight loss is not the appropriate outcome to evaluate the effects of exercise on abdominal adiposity and ectopic fat depots (e.g. liver fat and epi/pericardial fat) in eleven recreational middle-aged male cyclists (aged 50 to 66 years) without symptoms of cardiovascular disease. The main questions it aims to answer are:
- If energy intake is substantially increased to compensate energy expenditure and prevent weight loss following an extreme exercise prescription, will significant changes in body composition and body fat distribution be observed?
- Will these changes translate into improvements in the cardiometabolic health profile even in the absence of weight loss?
Participants will be asked to partake in several evaluations: fasting plasma lipoprotein-lipid profile and inflammation markers, glycated hemoglobin, cardiorespiratory fitness, submaximal exercise test including measurement of energy expenditure, resting and exercise blood pressure and heart rate, evaluation of regional adiposity, liver fat content, epi/pericardial fat, nutritional quality, and level of physical activity. After baseline evaluations, participants will be asked to alternately bike 208 km and 104 km per day on a pre-specified course for seven consecutive days. They will be accompanied during each of the seven bike rides by research professionals in a recreational vehicle. Participants' weight, body composition and waist circumference will be measured under standardized conditions in the morning after an overnight fast and after the exercise. Their heart rate will be continuously monitored, and participants will wear accelerometers to estimate their daily exercise-related energy expenditure. Foods and fluids will be provided to participants and recorded. At the end of the 1,144 km/ 7-days bike ride, baseline evaluations will be repeated with the exception of the maximal exercise treadmill test, nutritional quality, and level of physical activity. To facilitate the conduct of the protocol, the eleven participants will be evaluated and followed in two distinct groups.
Detailed description
Although there is robust evidence that a physically active lifestyle including regular leisure time physical activity and exercise (>150 min per week of moderate to vigorous exercise per week) is associated with a reduced mortality risk and improved cardiometabolic health, some scientists have promoted the notion (which has certainly been taken up by the lay press) that if one wants to lose weight, focus should be placed on caloric restriction rather than on exercise. Several academic debates have been held on this issue which have left some health professionals and the public confused and perplexed.
The investigators' research group has been active in this area on several fronts. First, the investigators have pioneered the notion that in cardiovascular and "metabolic" medicine, the health risk of overweight and obesity was not appropriately assessed by an index based on body weight (body mass index, which is expressed in kg/m^2). For instance, using imaging technology (computed tomography), the investigators were among the first, more than 30 years ago, to begin to extensively study regional body fat distribution, showing that excess visceral adipose tissue accumulation was more closely related to an atherogenic and diabetogenic cardiometabolic risk profile than excess body weight or total body fat. As sedentary individuals with a diet of poor nutritional value (rich in processed fat and added sugar - promoting preferential visceral fat deposition) are also often characterized by a lower muscle mass and by high levels of abdominal visceral fat, several lifestyle intervention studies that the investigators and others have conducted in sedentary males with visceral obesity have shown that with regular exercise, one could lose visceral adipose tissue while gaining muscle mass, which would lead to trivial or sometimes no changes in body weight. Thus, if body composition is altered by an energy deficit produced by regular exercise, the investigators have proposed that weight loss may sometime be misleading as an outcome as it may not always reflect favorable changes in body composition (muscle mass increasing) and in visceral adiposity and levels of ectopic fat (decreasing). On that basis, the investigators have proposed that changes in waist circumference could be more useful than body weight loss in the evaluation of the benefits of a lifestyle modification program involving regular endurance exercise such as brisk walking, jogging, or biking. For instance, the investigators have previously reported that waist circumference was rather sensitive to lifestyle changes involving regular physical activity/exercise. Accordingly, lifestyle intervention studies have shown that a reduction of 4 cm in waist girth was predictive of a 58% reduction in the risk of developing type 2 diabetes among individuals who were initially characterized by abdominal obesity and glucose intolerance.
Thus, there is a need to propose a paradigm shift among health professionals to evaluate the impact of lifestyle intervention programs involving physical activity/exercise in high-risk overweight obese individuals with visceral obesity: Weight loss is no longer the optimal or most clinically relevant outcome - losses of visceral adiposity and ectopic fat may be more relevant clinically.
In 2015, a member of the investigators' team was asked to write an editorial on a spectacular study which provided very relevant data to the debate about diet vs. exercise and weight loss. In that impressive exercise study, recreational middle-aged cyclists were required to bike 2,700 km over 14 days and asked to try to match their energy intake to their very large energy expenditure, the objective being not to lose weight over the course of the intervention. Thus, the daily exercise "prescription" was huge as the authors wanted to test the ability of these elderly and fit recreational cyclists to match their energy intake to their energy expenditure. The most striking and important finding of this unusual study is that despite the huge energy expenditure associated with the 2,700 km bike expedition, participants did not lose weight. However, such lack of change in body weight was completely misleading in terms of energy balance and changes in body composition. Indeed, the cyclists lost 2.2 kg of body fat while gaining 2.5 kg of fat-free mass, a remarkable finding considering that such changes were observed over a period of only two weeks.
Results of this study provide additional evidence that body weight is a poor outcome to assess the effect of a physical activity/exercise program. In the investigators' previously published exercise training studies, a common observation has been the disconnect between changes in body weight and changes in body composition, the latter being sometime observed even in the absence of weight loss. As weight poorly tracks changes in body composition induced by exercise, no wonder why exercise is indeed perceived as not being helpful to lose weight by some health professionals. The investigators propose that body weight is a misleading outcome when comes the time to evaluate the clinical benefits of exercise in individuals with overweight/obese.
One remaining and clinically important issue remains to be addressed regarding the effects of a large volume of exercise not inducing weight loss: to what extent substantial changes in visceral/ectopic fat could have been observed had imaging data been available? In addition, it would have been interesting for the 2,700 km bike intervention study to report changes in waist circumference, this metric being more sensitive to regular exercise than body weight. In the investigators' previous intervention studies, it has been their experience to find participants losing quite a bit of visceral fat and dropping their waistline by several centimeters, while not losing any body weight.
Thus, on the basis of the above observations, the investigators put forward the hypotheses that:
- a very large volume of exercise (1,144 km of bicycle performed for 7 consecutive days) will induce major changes in body composition and in levels of visceral adipose tissue/ectopic fat in a sample of middle-aged recreational cyclists who will be asked to match their energy intake to their very large energy expenditure during the course of the one-week extreme exercise intervention. Thus, in a study where, by design, no weight loss is planned nor wanted, the investigators expect to see major changes in body composition (slight increase in muscle mass and substantial reductions in the size of visceral adipose tissue and ectopic fat depots);
- changes in levels of visceral adipose tissue and ectopic fat will be better reflected by changes in waist circumference - which should decrease in the absence of body weight loss.
The investigators recognize that this is an extreme exercise prescription that has little relevance to public health. However, results of this study will be very important in shedding light on the importance of shifting our attention from body weight loss to other, more clinically relevant fat depots. Thus, the purpose of the study is to provide evidence, through an extreme exercise prescription, that weight loss is not the appropriate outcome to evaluate the effects of exercise on visceral adiposity and ectopic fat depots (e.g. liver fat and epi/pericardial fat) which will likely be mobilized to a very significant extent in only one week.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Extreme exercise group | Experimental | Behavioral: High-volume road cycling1,144 km of road cycling on seven consecutive days |
Who may qualify
- Ages
- 50 to 66 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male
- Between the ages of 50 and 66 years
- Asymptomatic for cardiovascular disease
- Reporting at least 5,000 km per year of road cycling at an average pace of about 30 km/h
Key exclusion criteria (5 listed)
- Retired competitive athletes/competitive athletes
- Undergoing hormonal or corticosteroid therapy
- Presenting a cancer not in remission
- Presenting an absolute contraindication to MRI
- Presenting an absolute contraindication to maximal cardiopulmonary exercise testing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-volume road cycling1,144 km of road cycling performed on seven consecutive days with an increase in energy intake to maintain a stable body weight | Behavioural | Extreme exercise group |
Primary outcome
Changes from baseline in body weight assessed by direct segmental multi-frequency bioimpedance analysis following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes in body weight in kilograms
Changes from baseline in fat mass assessed by direct segmental multi-frequency bioimpedance analysis following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes in fat mass in kilograms
Changes from baseline in fat-free mass assessed by direct segmental multi-frequency bioimpedance analysis following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes in fat-free mass in kilograms
Changes from baseline in body water assessed by direct segmental multi-frequency bioimpedance analysis following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes in body water in kilograms
Changes from baseline in waist circumference assessed using a standardized measuring tape following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes in waist circumference in centimeters
Changes from baseline in visceral adipose tissue assessed using magnetic resonance imaging following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes in visceral adipose tissue in milliliters
Changes from baseline in subcutaneous adipose tissue assessed using magnetic resonance imaging following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes in subcutaneous adipose tissue in milliliters
Changes from baseline in epicardial adipose tissue assessed using magnetic resonance imaging following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes in epicardial adipose tissue in milliliters
Changes from baseline in pericardial adipose tissue assessed using magnetic resonance imaging following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes in pericardial adipose tissue in milliliters
Changes from baseline in liver fat content assessed using magnetic resonance imaging with spectroscopy following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes in liver fat content in percentage
14 secondary outcomes
Changes from baseline in fasting total cholesterol following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting LDL cholesterol following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting HDL cholesterol following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting plasma triglycerides following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting glycated hemoglobin following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting apolipoprotein A1 following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting apolipoprotein B following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting adiponectin following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting leptin following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting C-reactive protein following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting interleukin-6 following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in fasting tumor necrosis factor alpha following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in resting systolic blood pressure following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Changes from baseline in resting diastolic blood pressure following the extreme exercise prescription
Time frame: Before and the day (or next day) following the extreme exercise prescription
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2023.
- Background: PubMed 25918126Kraus WE, Bittner V, Appel L, Blair SN, Church T, Despres JP, Franklin BA, Miller TD, Pate RR, Taylor-Piliae RE, Vafiadis DK, Whitsel L; American Heart Association Physical Activity Committee of the Council on Lifestyle and Metabolic Health, Council on Clinical Cardiology, Council on Hypertension, and Council on Cardiovascular and Stroke Nursing. The National Physical Activity Plan: a call to action from the American Heart Association: a science advisory from the American Heart Association. Circulation. 2015 May 26;131(21):1932-40. doi: 10.1161/CIR.0000000000000203. Epub 2015 Apr 27. No abstract available.
- Background: PubMed 24415616Luke A, Cooper RS. Physical activity does not influence obesity risk: time to clarify the public health message. Int J Epidemiol. 2013 Dec;42(6):1831-6. doi: 10.1093/ije/dyt159. No abstract available.
- Background: PubMed 25904145Malhotra A, Noakes T, Phinney S. It is time to bust the myth of physical inactivity and obesity: you cannot outrun a bad diet. Br J Sports Med. 2015 Aug;49(15):967-8. doi: 10.1136/bjsports-2015-094911. Epub 2015 Apr 22. No abstract available.
- Background: PubMed 24415617Blair SN, Archer E, Hand GA. Commentary: Luke and Cooper are wrong: physical activity has a crucial role in weight management and determinants of obesity. Int J Epidemiol. 2013 Dec;42(6):1836-8. doi: 10.1093/ije/dyt160. No abstract available.
- Background: PubMed 26062953Blair SN. Physical inactivity and obesity is not a myth: Dr. Steven Blair comments on Dr. Aseem Malhotra's editorial. Br J Sports Med. 2015 Aug;49(15):968-9. doi: 10.1136/bjsports-2015-094989. Epub 2015 Jun 10. No abstract available.
- Background: PubMed 2196040Despres JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis. 1990 Jul-Aug;10(4):497-511. doi: 10.1161/01.atv.10.4.497.
- Background: PubMed 18356555Despres JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodes-Cabau J, Bertrand OF, Poirier P. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1039-49. doi: 10.1161/ATVBAHA.107.159228. Epub 2008 Mar 20.
- Background: PubMed 22949540Despres JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012 Sep 4;126(10):1301-13. doi: 10.1161/CIRCULATIONAHA.111.067264. No abstract available.
- Background: PubMed 22262155Borel AL, Nazare JA, Smith J, Almeras N, Tremblay A, Bergeron J, Poirier P, Despres JP. Visceral and not subcutaneous abdominal adiposity reduction drives the benefits of a 1-year lifestyle modification program. Obesity (Silver Spring). 2012 Jun;20(6):1223-33. doi: 10.1038/oby.2011.396. Epub 2012 Jan 19.
- Background: PubMed 10896648Ross R, Dagnone D, Jones PJ, Smith H, Paddags A, Hudson R, Janssen I. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Ann Intern Med. 2000 Jul 18;133(2):92-103. doi: 10.7326/0003-4819-133-2-200007180-00008.
- Background: PubMed 25661557Despres JP. Obesity and cardiovascular disease: weight loss is not the only target. Can J Cardiol. 2015 Feb;31(2):216-22. doi: 10.1016/j.cjca.2014.12.009. Epub 2014 Dec 11.
- Background: PubMed 11832527Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Natalie Alméras, Ph.D. principal investigator
Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-volume road cycling in people with Cardiovascular Diseases and Obesity, Visceral, run by Institut universitaire de cardiologie et de pneumologie de Québec, University Laval at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes from baseline in body weight assessed by direct segmental multi-frequency bioimpedance analysis following the extreme exercise prescription (time frame: Before and the day (or next day) following the extreme exercise prescription). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05895916, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2023.