Clinical trial NCT04477590: Interactions of Medicine and Exercise With Meal Timing
Official title: Optimizing Exercise Training Effects on Metabolic Syndrome Factors by Altering the Timing of Medication and Meal Ingestion
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Metabolic Syndrome, Protection Against
Exercise Training
Metformin
Statins
Angiotensin-Converting-Enzyme Inhibitor
Fasting, Intermittent
Angiotensin Hypertension
Keywords: Cardiorespiratory fitness
Insulin sensitivity
Dyslipidemia
Hypertension
Lead sponsor: University of Castilla-La Mancha
Sponsor class: OTHER
Collaborators: name: Ministerio de Economía y Competitividad, Spain
name: Servicio de Salud de Castilla-La Mancha
First posted: 2020-07-20
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Cross-over randomized, pretest-posttest control group experimental design.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Insulin sensitivity assessed using intravenous glucose tolerance test
timeFrame: 12 months
measure: Post-prandial lipemia assessed by an oral fat tolerance test
timeFrame: 12 months
measure: Blood pressure assessed by ECG-gated automated sphygmomanometer
timeFrame: 12 months
measure: Glycemic control assessed by 24-h continuous interstitial glucose monitoring
timeFrame: 36 months
Secondary outcomes:
measure: Body composition.
timeFrame: 12 months
measure: Body mass index
timeFrame: 12 months
measure: Maximal oxygen consumption during a graded exercise test to exhaustion, assessed by indirect calorimetry
timeFrame: 12 months
measure: Resting metabolic rate assessed by indirect calorimetry while lying after an overnight fast
timeFrame: 12 months
measure: Maximal rate of fat oxidation assessed by indirect calorimetry during a submaximal exercise test.
timeFrame: 12 months
measure: 24-hour monitoring of blood concentrations of metformin, statins, and angiotensin blockers assessed using gas chromatography-mass spectrometry.
timeFrame: 36 months
measure: The activity of intramuscular proteins (enzymes) involved in energetics assessed using western blots.
timeFrame: 36 months
Other outcomes:
Locations:
city: Toledo
country: Spain
facility: University of Castilla-La Mancha (Exercise Physiology Lab)
Study officials:
affiliation: University of Castilla-La Mancha
name: RICARDO M Mora-Rodriguez, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ortega JF, Hamouti N, Fernandez-Elias VE, de Prada MV, Martinez-Vizcaino V, Mora-Rodriguez R. Metformin does not attenuate the acute insulin-sensitizing effect of a single bout of exercise in individuals with insulin resistance. Acta Diabetol. 2014 Oct;51(5):749-55. doi: 10.1007/s00592-014-0580-4. Epub 2014 Mar 29.
citation: Mora-Rodriguez R, Ortega JF, Guio de Prada V, Fernandez-Elias VE, Hamouti N, Morales-Palomo F, Martinez-Vizcaino V, Nelson RK. Effects of Simultaneous or Sequential Weight Loss Diet and Aerobic Interval Training on Metabolic Syndrome. Int J Sports Med. 2016 Apr;37(4):274-81. doi: 10.1055/s-0035-1564259. Epub 2015 Dec 14.
citation: Alvarez-Jimenez L, Moreno-Cabanas A, Ramirez-Jimenez M, Morales-Palomo F, Ortega JF, Mora-Rodriguez R. Effects of statins and exercise on postprandial lipoproteins in metabolic syndrome vs metabolically healthy individuals. Br J Clin Pharmacol. 2021 Mar;87(3):955-964. doi: 10.1111/bcp.14447. Epub 2020 Jul 12.
citation: Mora-Rodriguez R, Ortega JF, Morales-Palomo F, Ramirez-Jimenez M, Moreno-Cabanas A. Effects of statin therapy and exercise on postprandial triglycerides in overweight individuals with hypercholesterolaemia. Br J Clin Pharmacol. 2020 Jun;86(6):1089-1099. doi: 10.1111/bcp.14217. Epub 2020 Feb 18.
citation: Morales-Palomo F, Ramirez-Jimenez M, Ortega JF, Moreno-Cabanas A, Mora-Rodriguez R. Exercise Training Adaptations in Metabolic Syndrome Individuals on Chronic Statin Treatment. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz304. doi: 10.1210/clinem/dgz304.
citation: Guio de Prada V, Ortega JF, Morales-Palomo F, Ramirez-Jimenez M, Moreno-Cabanas A, Mora-Rodriguez R. Women with metabolic syndrome show similar health benefits from high-intensity interval training than men. PLoS One. 2019 Dec 10;14(12):e0225893. doi: 10.1371/journal.pone.0225893. eCollection 2019.
citation: Moreno-Cabanas A, Ortega JF, Morales-Palomo F, Ramirez-Jimenez M, Mora-Rodriguez R. Importance of a verification test to accurately assess V̇O2 max in unfit individuals with obesity. Scand J Med Sci Sports. 2020 Mar;30(3):583-590. doi: 10.1111/sms.13602. Epub 2019 Dec 11.
citation: Morales-Palomo F, Ramirez-Jimenez M, Ortega JF, Mora-Rodriguez R. Effectiveness of Aerobic Exercise Programs for Health Promotion in Metabolic Syndrome. Med Sci Sports Exerc. 2019 Sep;51(9):1876-1883. doi: 10.1249/MSS.0000000000001983.
citation: Mora-Rodriguez R, Ortega JF, Ramirez-Jimenez M, Moreno-Cabanas A, Morales-Palomo F. Insulin sensitivity improvement with exercise training is mediated by body weight loss in subjects with metabolic syndrome. Diabetes Metab. 2020 Jun;46(3):210-218. doi: 10.1016/j.diabet.2019.05.004. Epub 2019 May 31.
citation: Mora-Rodriguez R, Ortega JF, Morales-Palomo F, Ramirez-Jimenez M. Weight loss but not gains in cardiorespiratory fitness after exercise-training predicts improved health risk factors in metabolic syndrome. Nutr Metab Cardiovasc Dis. 2018 Dec;28(12):1267-1274. doi: 10.1016/j.numecd.2018.08.004. Epub 2018 Aug 23.
citation: Ramirez-Jimenez M, Morales-Palomo F, Ortega JF, Mora-Rodriguez R. Effects of intense aerobic exercise and/or antihypertensive medication in individuals with metabolic syndrome. Scand J Med Sci Sports. 2018 Sep;28(9):2042-2051. doi: 10.1111/sms.13218. Epub 2018 Jun 4.