Interactions of Medicine and Exercise With Meal Timing

Study Overview
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Brief Summary
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To analyze the effects of altering the time of ingestion of participants' habitual medication (i.e., metformin, statins, ARAII/IACE) and meals around the time of exercise training (exercise fasted or fed) on the improvement of metabolic syndrome factors (hypertension, insulin sensitivity, dyslipidemia, and obesity). There will be a preliminary study of the effects of training time-of-day on the primary study outcomes.

Detailed Description
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Objective: The purpose is to study in a group of adults with metabolic syndrome and obesity, the effects of altering timing between exercise training, meals, and their habitual medication on the improvement in the factors that compose the metabolic syndrome (i.e., hypertension, insulin resistance, central obesity, and dyslipidemia). The main objective is to find the most productive combination between exercise training and the timing of their habitual pharmacological treatment, and meal ingestion for lowering those factors. Methods and design: Cross-over randomized double-blinded, pretest-posttest control group experimental design. The project will be developed in a single center with the collaboration of the regional public health system (SECAM). There will be a preliminary study of the effects of training time-of-day on three parallel groups of individuals. Subjects: Will be referred by their primary care physicians to our study unit or recruited by advertisements in local media. Up to 180 subjects, all of them with metabolic syndrome will be recruited (>25% women). Measurements: Specifically, we will study if the cardiovascular and metabolic adaptations to aerobic training that result in amelioration of metabolic syndrome factors are potentiated by correct timming of training, meals, and medicine around exercise training time.

Official Title
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Optimizing Exercise Training Effects on Metabolic Syndrome Factors by Altering the Timing of Medication and Meal Ingestion

Conditions
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Metabolic Syndrome, Protection Against, Exercise Training, Metformin, Statins, Angiotensin-Converting-Enzyme Inhibitor, Fasting, Intermittent, Angiotensin Hypertension

Intervention / Treatment
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* Drug: EXERCISE TRAINING WITH OR WITHOUT MEDICATION


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metabolic syndrome patients diagnosed according to The International diabetes federation consensus of 2009 (Alberti, et al., Circulation). Exclusion Criteria: Cardiovascular disease or musculo-skeletal that prevents them from being able to perform intense exercise. Respiratory failure Liver o renal disease Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Cross-over randomized, pretest-posttest control group experimental design.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: NO EXERCISE TRAINING<br>25-32 individuals with metabolic syndrome that will remain sedentary during the 4 months of treatment taking their habitual medication (i.e., blood pressure, glucose, cholesterol, and triglycerides lowering drugs) and meals at the habitual time (CONTROL GROUP). | |
| Experimental: EXERCISE TRAINING FED<br>2 groups of 25-32 individuals with metabolic syndrome that will exercise-train during 16 weeks after ingesting a liquid test meal (500 calls, 50% fat) 30 min before exercise (EXERCISE TRAINING FED). | Drug: EXERCISE TRAINING WITH OR WITHOUT MEDICATION<br>* A group will train 30 min after taking their habitual dose of medicine (MEDICATED train) while another group will train after taking a placebo (NON-MEDICATED train) and will receive their medication after training.<br>* Other names: Exercise timing with respect to medication (metformin, statins, ARAII/ACEI);|
| Experimental: EXERCISE TRAINING FASTED<br>2 groups of 25-32 individuals with metabolic syndrome that will exercise-train during 16 weeks after ingestion of a placebo meal (0 kcals) 30 min before exercise (EXERCISE TRAINING FAST). | Drug: EXERCISE TRAINING WITH OR WITHOUT MEDICATION<br>* A group will train 30 min after taking their habitual dose of medicine (MEDICATED train) while another group will train after taking a placebo (NON-MEDICATED train) and will receive their medication after training.<br>* Other names: Exercise timing with respect to medication (metformin, statins, ARAII/ACEI);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity assessed using intravenous glucose tolerance test | Curves of insulin-mediated glucose clearance, inhibition of lipolysis, and liver glucose output measured with the use of stable isotope infusion. | 12 months | 
| Post-prandial lipemia assessed by an oral fat tolerance test | Rates of appearance and clearance of liver VLDL-TG, Apolipoprotein B, and fatty acids using stable isotopes. | 12 months | 
| Blood pressure assessed by ECG-gated automated sphygmomanometer | Determined immediately after treatments and during the following 24-h using ambulatory blood pressure Holter-type monitors. | 12 months | 
| Glycemic control assessed by 24-h continuous interstitial glucose monitoring | Determined by a patch glucose sensor paired with a glucose monitor. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition. | Determined by bioelectrical impedance to calculate body fat mass and fat free mass. | 12 months | 
| Body mass index | Determined by body weight (kg) and height (m) to calculate body mass index (kg/m2) | 12 months | 
| Maximal oxygen consumption during a graded exercise test to exhaustion, assessed by indirect calorimetry | Calculation of cardiorespitarory fitness | 12 months | 
| Resting metabolic rate assessed by indirect calorimetry while lying after an overnight fast | Using indirect calorimetry and a ventilated canopy system | 12 months | 
| Maximal rate of fat oxidation assessed by indirect calorimetry during a submaximal exercise test. | Calculated in grams per min during the incremental cycle ergometer test with the use of indirect calorimetry system | 12 months | 
| 24-hour monitoring of blood concentrations of metformin, statins, and angiotensin blockers assessed using gas chromatography-mass spectrometry. | To study the pharmacokinetics of the habitual medicines used by our subjects during the different experimental conditions | 36 months | 
| The activity of intramuscular proteins (enzymes) involved in energetics assessed using western blots. | Measured in skeletal muscle obtained by percutaneous muscle biopsy. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiorespiratory fitness, Insulin sensitivity, Dyslipidemia, Hypertension