Role of Fasted Exercise on Improving Cardiometabolic Health

Study Overview
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Brief Summary
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The aim of this randomised control trial is to investigate the role of fasted exercise on cardiometabolic health. Participants will be assigned to one of three conditions, fasted exercise, fed exercise and control (no exercise). Participants in the exercise groups will complete four weeks of moderate intensity cycling exercise, three times per week, either in the fasted or fed state according to their group assignment. Experimental trials involving anthropometric and cardiometabolic disease risk factor measurements as well as metabolic responses to a subsequent meal ingestion following exercise will be compared pre-intervention and post intervention.

Detailed Description
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The aim of this study is to investigate the effect of fasted exercise on cardiometabolic health and the potential mediatory role of sirtuins. The objectives are to investigate: The effect of a single bout of fasted exercise on acute metabolic responses following a high fat meal. The effect of four weeks of fasted exercise training on cardiovascular and metabolic disease risk factors. The effect of four weeks of fasted exercise training on circulating levels and subcutaneous adipose tissue gene expression of SIRT1, SIRT3 and SIRT6. A randomised control trial will be conducted with volunteers allocated under the conditions of a) no exercise (control), b) fasted exercise training (FASTEX) and c) fed exercise training (FEDEX). The pre- and post-intervention visits will consist of 50 minutes of cycling at a moderate exercise intensity for both the FASTEX and FEDEX groups. The control group would not perform any exercise. The FASTEX group will perform the exercise in the fasted state, whilst the FEDEX and control groups will be fed a standardised breakfast meal one hour in advance of the exercise period. Following the exercise period, the participants will be fed a high fat meal and metabolic responses to the meal will be measured for four hours. Multiple blood samples will be obtained as well as a sample of subcutaneous adipose (fat) tissue. The FASTEX and FEDEX groups will then complete four weeks of moderate intensity continuous exercise training, either fasted or fed according to their group, on three days per week whilst the control group will maintain their normal sedentary lifestyle. All participants will return to the laboratory for post-intervention testing at the end of the four weeks with the same protocols and measurements as the pre-intervention testing.

Official Title
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Investigating the Role of Fasted Exercise on Improving Cardiometabolic Health; a Potential Mediatory Role of Sirtuins

Conditions
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Cardiovascular Diseases, Diabetes Mellitus, Type 2, Obesity

Intervention / Treatment
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* Other: Exercise training in the fasted state
* Other: Exercise training in the fed state


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Non-smokers Physically inactive (partake in no more than one exercise session per week on average) Body mass index >18.5 kg/m2 Healthy as assessed by medical screening questionnaire Prior recipient of local anaesthetic with no known adverse effects, no known hypersensitivity or no other health issue that may constrain the administration of lidocaine hydrochloride Free from musculoskeletal injury and able to perform cycling exercise Capacity to give informed consent Exclusion Criteria: Regular exerciser BMI < 18.5 kg/m2 Pregnant Allergy or intolerances to test meal products/ingredients (such as wheat or dairy products). Recent major body weight change (+/- 3 kg in the past month) Known hypersensitivity to Lidocaine Hydrochloride Cardiovascular disease - complete heart block or hypovolaemia Adam's-Stokes Syndrome Wolff-Parkinson-White Syndrome Porphyria Epilepsy Myasthenia Gravis Other chronic medical condition or diagnosis including respiratory (eg asthma), endocrine, cardiovascular, neuromuscular disorders. Taking medications or receiving treatment that may constrain the administration of lidocaine or local anaesthesia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

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: Parallel Assignment
Interventional Model Description: Randomised control
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fasted exercise<br>Exercise training in the fasted state | Other: Exercise training in the fasted state<br>* Four weeks of moderate intensity cycling exercise, three times a week without eating breakfast meal<br>|
| Active Comparator: Fed exercise<br>Exercise training in the fed state | Other: Exercise training in the fed state<br>* Four weeks of moderate intensity cycling exercise, three times a week, after eating breakfast meal<br>|
| No Intervention: Control<br>No exercise training | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in circulating concentrations of key metabolic markers following a high fat lunch meal | Serum concentrations of clinical chemistry blood analytes (glucose, triglycerides, cholesterol) | 9 blood samples collected at pre-meal ingestion then every 30 min after ingestion for four hours | 
| Changes in circulating concentrations of key metabolic markers during the experimental trial day | Serum concentrations of clinical chemistry blood analytes (glucose, triglycerides, cholesterol) | 12 blood samples collected at 0 (baseline), 75 (pre-exercise), 125 (immediately post-exercise), 155 min (pre-meal ingestion) then every 30 min after ingestion for four hours | 
| Area under the circulating concentration versus time curve (AUC) of key metabolic markers following a high fat lunch meal | Total responses of clinical chemistry blood analytes (glucose, triglycerides, cholesterol) | 4.5 hours | 
| Changes in cardiovascular and metabolic disease biochemistry risk factors | Fasted serum concentrations of clinical chemistry blood analytes (glucose, blood lipids, inflammatory markers) | 4 weeks (pre and post intervention) | 
| Changes in cardiovascular disease physiological risk factors | Systolic and diastolic blood pressure and calculation of mean arterial pressure using systolic and diastolic values | 4 weeks (pre and post intervention) | 
| Changes in concentration of sirtuin molecules | Serum concentrations of sirtuins | 4 weeks (pre and post intervention) | 
| Changes in sirtuin molecule gene expression | Adipose tissue gene expression of sirtuins | 4 weeks (pre and post intervention) | 
| Changes in sirtuin molecule tissue expression | Adipose tissue expression and cellular localisation of sirtuins | 4 weeks (pre and post intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cardiovascular and metabolic disease anthropometric risk factors | Waist circumference, hip circumference and waist:hip ratio | 4 weeks (pre and post intervention) | 
| Change in body composition | Body fat percentage measured using bioelectrical impedance analysis | 4 weeks (pre and post intervention) | 
| Change in body mass | Body mass in kilograms | 4 weeks (pre and post intervention) | 
| Change in substrate oxidation during the experimental trial day | Carbohydrate and fat oxidation through indirect calorimetry | 17 measurements at 0 (baseline), 15 (post-breakfast meal period), 45 (30 min post-breakfast meal period), 75 (pre-exercise), every 10 min during exercise, 155 (pre-meal ingestion), then every 30 min for four hours. | 
| Heart rate response to exercise | Heart rate during exercise in the experimental trial using telemetry | At rest before exercise then every 5 min during 50 min cycle exercise | 
| Perceived exertion | Rating of perceived exertion of exercise in the experimental trial using Borg scale | Every 5 min during 50 min cycle exercise | 
| Change in physical activity levels | Physical activity energy expenditure during the intervention period | Daily for 4 weeks | 
| Change in physical activity duration | Amount of time spent performing physical activity at different intensities (low, moderate, high) during the intervention period | Daily for 4 weeks | 
| Change in energy intake | Energy intake using weighed food diary record during the intervention period | Daily for 4 weeks | 
| Change in dietary nutritional intake | Macronutrient (carbohydrate, fat, protein) composition of food intake using weighed food diary record during the intervention period | Daily for 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular disease, Diabetes Mellitus, Obesity, Cardiometabolic health, Exercise, Fasted, Sirtuins