METSYND: Exercise Training Effects on Metabolic Syndrome: Interactions With Medication
Sponsor
University of Castilla-La Mancha (Other)
Overall Status
Completed
CT.gov ID
NCT03019796
Collaborator
Ministerio de Economía y Competitividad, Spain (Other)
40
1
2
61
0.7
Study Details
Study Description
Brief Summary
To analyze the effects of different exercise training modalities (continuous, intervallic, and resistance training) on cardiorespiratory and metabolic fitness of metabolic syndrome patients when this training interacts with their habitual medication.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
Objective: The purpose is to study in a group of adults with metabolic syndrome and obesity, the effects of different modalities of exercise training on cardiorespiratory and metabolic fitness. The main objective is to weight the effects of exercise training separately and in conjunction with the subject's habitual pharmacological treatment to identify the best combination of drug and exercise.
Methods and design: Randomized, pretest-posttest control group experimental design. Project developed in a single center with the collaboration of the regional public health system.
Subjects: Will be referred by their primary care physicians to our study unit. Up to 40 subjects all of them with metabolic syndrome will be recruited (at least 20% women).
Measurements:
-
Specifically, the investigators, will study cardiovascular adaptations that increase, i) maximal aerobic capacity measured by VO2max, ii) anaerobic and respiratory compensation point ventilatory thresholds, iii) arterial stiffness, measured by pulse wave velocity (SphygmoCor System), v) central and peripheral blood pressure, and iv) biological markers of endothelial dysfunction using reactive hyperemia with a laser Doppler fluxmeter in central and peripheral blood vessels.
-
The metabolic adaptations under study will include, i) insulin sensitivity by HOMA-IR,
- fat oxidation by indirect calorimetry
Study Design
Study Type:
Interventional
Actual Enrollment
:
40 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Effects of Exercise Training as a Non-pharmacological Treatment for Metabolic Syndrome and Its Interactions With Subjects Habitual Medications.
Actual Study Start Date
:
Jul 1, 2015
Actual Primary Completion Date
:
Apr 1, 2018
Actual Study Completion Date
:
Aug 1, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PLACEBO FIRST THEN MEDICATED Subjects first receive the PLACEBO tablet during 72 hours (full withdrawal). After a week of taking again their medication (MEDICATION TRIAL), they will be tested again. This procedure will be repeated before and after 4 months of aerobic training. |
Drug: MEDICATION AND EXERCISE TRAINING
PARTICIPANTS WILL BE (IN A RANDOMIZED BLINDED FASHION) WITHDRAWN OF THEIR HYPERTENSIVE MEDICATION (I.E., PLACEBO) IN ONE OCCASION AND TESTED WITH THEIR MEDICATION IN ANOTHER, WITH A WEEK WASHOUT PERIOD.
THIS TESTING WILL BE REPEATED AFER 4 MONTHS OF EXERCISE TRAINING (48 SESSIONS OF 43 MIN EACH ONE).
|
| Experimental: MEDICATED FIRST THEN PLACEBO Subjects first receive their antihypertensive MEDICATION tablet (habitual dose prescribed by their primary care doctors). After a week they will take a PLACEBO tablet for 72 hours and will be tested again. This procedure will be repeated before and after 4 months of aerobic training. |
Drug: MEDICATION AND EXERCISE TRAINING
PARTICIPANTS WILL BE (IN A RANDOMIZED BLINDED FASHION) WITHDRAWN OF THEIR HYPERTENSIVE MEDICATION (I.E., PLACEBO) IN ONE OCCASION AND TESTED WITH THEIR MEDICATION IN ANOTHER, WITH A WEEK WASHOUT PERIOD.
THIS TESTING WILL BE REPEATED AFER 4 MONTHS OF EXERCISE TRAINING (48 SESSIONS OF 43 MIN EACH ONE).
|
Outcome Measures
Primary Outcome Measures
- Systolic Blood Pressure [Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours.]
Determined using a ECG-gated automated sphygmomanometer. Value is the difference between the placebo and antihypertensive medication.
- Diastolic Blood Pressure [Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours.]
Determined using a ECG-gated automated sphygmomanometer. Value is the difference between the placebo and antihypertensive medication.
- Mean Arterial Pressure [Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours.]
Determined using a ECG-gated automated sphygmomanometer. Value is the difference between the placebo and antihypertensive medication.
Secondary Outcome Measures
- Maximal Oxygen Consumption Rate During Exercise (VO2max). [Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours.]
Index of cardiorespiratory fitness assessed during an incremental cycle-ergometer test using an indirect calorimetry system. Value is the difference between the placebo and antihypertensive medication.
- Maximal Rate of Fat Oxidation. [Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours.]
Calculated in grams per min during the incremental cycloergometer test wih the use of indirect calorimetry system. Value is the difference between the placebo and antihypertensive medication.
- Body Weight [Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours.]
Nude body weight. Value is the difference between the placebo and antihypertensive medication.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Metabolic syndrome patients diagnosed according to the International diabetes federation consensus of 2009 (Alberti, et al., Circulation).
-
18-65 years old
Exclusion Criteria:
Cardiovascular disease or musculo-skeletal that prevents them from being able to perform intense exercise.
-
Respiratory failure
-
Patient ends
-
Pregnancy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Castilla-La Mancha (Exercise Physiology Lab) | Toledo | Spain | 45071 |
Sponsors and Collaborators
- University of Castilla-La Mancha
- Ministerio de Economía y Competitividad, Spain
Investigators
- Principal Investigator: Ricardo Mora-Rodriguez, PhD, University of Castilla-La Mancha
Study Documents (Full-Text)
More Information
Publications
- Díez-Fernández A, Sánchez-López M, Mora-Rodríguez R, Notario-Pacheco B, Torrijos-Niño C, Martínez-Vizcaíno V. Obesity as a mediator of the influence of cardiorespiratory fitness on cardiometabolic risk: a mediation analysis. Diabetes Care. 2014;37(3):855-62. doi: 10.2337/dc13-0416. Epub 2013 Nov 6.
- Martínez-Vizcaíno V, Sánchez-López M, Notario-Pacheco B, Salcedo-Aguilar F, Solera-Martínez M, Franquelo-Morales P, López-Martínez S, García-Prieto JC, Arias-Palencia N, Torrijos-Niño C, Mora-Rodríguez R, Rodríguez-Artalejo F. Gender differences on effectiveness of a school-based physical activity intervention for reducing cardiometabolic risk: a cluster randomized trial. Int J Behav Nutr Phys Act. 2014 Dec 10;11:154. doi: 10.1186/s12966-014-0154-4.
- Morales-Palomo F, Ramirez-Jimenez M, Ortega JF, Pallares JG, Mora-Rodriguez R. Cardiovascular Drift during Training for Fitness in Patients with Metabolic Syndrome. Med Sci Sports Exerc. 2017 Mar;49(3):518-526. doi: 10.1249/MSS.0000000000001139.
- Mora-Rodriguez R, Ortega JF, Guio de Prada V, Fernández-Elías 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.
- Mora-Rodriguez R, Ortega JF, Hamouti N, Fernandez-Elias VE, Cañete Garcia-Prieto J, Guadalupe-Grau A, Saborido A, Martin-Garcia M, Guio de Prada V, Ara I, Martinez-Vizcaino V. Time-course effects of aerobic interval training and detraining in patients with metabolic syndrome. Nutr Metab Cardiovasc Dis. 2014 Jul;24(7):792-8. doi: 10.1016/j.numecd.2014.01.011. Epub 2014 Jan 29.
- Ortega JF, Fernández-Elías VE, Hamouti N, Pallarés JG, Mora-Rodriguez R. Higher insulin-sensitizing response after sprint interval compared to continuous exercise. Int J Sports Med. 2015 Mar;36(3):209-14. doi: 10.1055/s-0034-1389942. Epub 2014 Nov 6.
- Ortega JF, Fernández-Elías VE, Hamouti N, Pallares JG, Mora-Rodriguez R. Higher Insulin-sensitizing Response after Sprint Interval Compared to Continuous Exercise. Int J Sports Med. 2015 Mar;36(3):e4. doi: 10.1055/s-0035-1548800. Epub 2015 Mar 26.
- Ortega JF, Hamouti N, Fernández-Elías VE, de Prada MV, Martínez-Vizcaíno V, Mora-Rodríguez 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.
- Ortega JF, Hamouti N, Fernández-Elías VE, Mora-Rodriguez R. Comparison of glucose tolerance tests to detect the insulin sensitizing effects of a bout of continuous exercise. Appl Physiol Nutr Metab. 2014 Jul;39(7):787-92. doi: 10.1139/apnm-2013-0507. Epub 2014 Apr 11.
- Ortega JF, Morales-Palomo F, Fernandez-Elias V, Hamouti N, Bernardo FJ, Martin-Doimeadios RC, Nelson RK, Horowitz JF, Mora-Rodriguez R. Dietary supplementation with omega-3 fatty acids and oleate enhances exercise training effects in patients with metabolic syndrome. Obesity (Silver Spring). 2016 Aug;24(8):1704-11. doi: 10.1002/oby.21552. Epub 2016 Jun 29.
Responsible Party:
University of Castilla-La Mancha
ClinicalTrials.gov Identifier:
NCT03019796
Other Study ID Numbers:
- 0112001154 DEP2014-52930-R
First Posted:
Jan 13, 2017
Last Update Posted:
Jun 14, 2021
Last Verified:
May 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | All participants underwent four trials in a full cross-over randomized fashion. Subject tested before and after 4 months of training. At baseline subjects were tested on two occasions, one with and one without medication separated 72 hours. Post-training testing was similarly conducted with and without medication separated 72 hours. |
| Arm/Group Title | MEDICATED FIRST THEN PLACEBO | PLACEBO FIRST THEN MEDICATED |
|---|---|---|
| Arm/Group Description | Subjects will remain taking their habitual antihypertensive medication during this time. After this first test, they will receive placebo during 72 h and will be tested again. | Subjects will be withdrawn from their habitual antihypertensive medication during 72 hours, which will be substituted by a placebo. Then their habitual medication will be restated and they will be tested again. |
| Period Title: First Intervention Drug Tests | ||
| STARTED | 20 | 20 |
| COMPLETED | 20 | 20 |
| NOT COMPLETED | 0 | 0 |
| Period Title: First Intervention Drug Tests | ||
| STARTED | 20 | 20 |
| COMPLETED | 19 | 19 |
| NOT COMPLETED | 1 | 1 |
| Period Title: First Intervention Drug Tests | ||
| STARTED | 19 | 19 |
| COMPLETED | 19 | 19 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | PRE-POST TRAINING |
|---|---|
| Arm/Group Description | In this cross over design, participants will be tested PRE and POST 4 months of endurance training. They will be tested while taking their habitual medication on one occasion and in the other, the investigators will withhold their medication during 72 h to achieve 4 conditions: Untrained, no medicated. Untrained, medicated. a) Trained, no medicated. b) Trained, medicated. |
| Overall Participants | 40 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
58.7
(5.5)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
8
20%
|
| Male |
32
80%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
40
100%
|
| Not Hispanic or Latino |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
40
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| Spain |
40
100%
|
Outcome Measures
| Title | Systolic Blood Pressure |
|---|---|
| Description | Determined using a ECG-gated automated sphygmomanometer. Value is the difference between the placebo and antihypertensive medication. |
| Time Frame | Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants underwent four trials in a full cross-over randomized fashion |
| Arm/Group Title | MEDICATED | PLACEBO |
|---|---|---|
| Arm/Group Description | Subjects will take their habitual dose of antihypertensive medication. | Subjects will be withdrawn from their habitual antihypertensive medication during 72 hours, which will be substituted by a placebo. |
| Measure Participants | 38 | 38 |
| BEFORE TRAINING |
126
(13)
|
134
(11)
|
| AFTER TRAINING |
124
(13)
|
133
(12)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MEDICATED, PLACEBO |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.040 |
| Comments | ||
| Method | ANOVA | |
| Comments | repeated measures | |
| Title | Diastolic Blood Pressure |
|---|---|
| Description | Determined using a ECG-gated automated sphygmomanometer. Value is the difference between the placebo and antihypertensive medication. |
| Time Frame | Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MEDICATED | PLACEBO |
|---|---|---|
| Arm/Group Description | Subjects will be tested while taking their habitual antihypertensive medication. | Subjects will be withdrawn from their habitual antihypertensive medication during 72 hours, which will be substituted by a placebo. |
| Measure Participants | 38 | 38 |
| BEFORE TRAINING |
75
(8)
|
79
(8)
|
| AFTER TRAINING |
72
(7)
|
77
(7)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MEDICATED, PLACEBO |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.054 |
| Comments | ||
| Method | ANOVA | |
| Comments | repeated measures | |
| Title | Mean Arterial Pressure |
|---|---|
| Description | Determined using a ECG-gated automated sphygmomanometer. Value is the difference between the placebo and antihypertensive medication. |
| Time Frame | Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MEDICATED | PLACEBO |
|---|---|---|
| Arm/Group Description | Subjects will be tested while taking their habitual antihypertensive medication. | Subjects will be withdrawn from their habitual antihypertensive medication during 72 hours, which will be substituted by a placebo. |
| Measure Participants | 38 | 38 |
| BEFORE TRAINING |
92
(9)
|
97
(8)
|
| AFTER TRAINING |
89
(8)
|
96
(8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MEDICATED, PLACEBO |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.040 |
| Comments | ||
| Method | ANOVA | |
| Comments | REPEATED MEASURES | |
| Title | Maximal Oxygen Consumption Rate During Exercise (VO2max). |
|---|---|
| Description | Index of cardiorespiratory fitness assessed during an incremental cycle-ergometer test using an indirect calorimetry system. Value is the difference between the placebo and antihypertensive medication. |
| Time Frame | Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MEDICATED | PLACEBO |
|---|---|---|
| Arm/Group Description | Subjects will be tested while taking their habitual antihypertensive medication. | Subjects will be withdrawn from their habitual antihypertensive medication during 72 hours, which will be substituted by a placebo. |
| Measure Participants | 38 | 38 |
| BEFORE TRAINING |
2.26
(0.58)
|
2.26
(0.58)
|
| AFTER TRAINING |
2.49
(0.55)
|
2.49
(0.55)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MEDICATED, PLACEBO |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.321 |
| Comments | ||
| Method | ANOVA | |
| Comments | REPEATED MEASURES | |
| Title | Maximal Rate of Fat Oxidation. |
|---|---|
| Description | Calculated in grams per min during the incremental cycloergometer test wih the use of indirect calorimetry system. Value is the difference between the placebo and antihypertensive medication. |
| Time Frame | Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MEDICATED | PLACEBO |
|---|---|---|
| Arm/Group Description | Subjects will be tested while taking their habitual antihypertensive medication. | Subjects will be withdrawn from their habitual antihypertensive medication during 72 hours, which will be substituted by a placebo. |
| Measure Participants | 38 | 38 |
| BEFORE TRAINING |
0.24
(0.10)
|
0.24
(0.10)
|
| AFTER TRAINING |
0.28
(0.15)
|
0.28
(0.15)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MEDICATED |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.401 |
| Comments | ||
| Method | ANOVA | |
| Comments | REPEATED MEASURES | |
| Title | Body Weight |
|---|---|
| Description | Nude body weight. Value is the difference between the placebo and antihypertensive medication. |
| Time Frame | Subject tested before and after 4 months of training. At baseline tested with and without medication separated 72 hours. Post training tested with and without medication separated 72 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MEDICATED | PLACEBO |
|---|---|---|
| Arm/Group Description | Subjects will be tested while taking their habitual antihypertensive medication. | Subjects will be withdrawn from their habitual antihypertensive medication during 72 hours, which will be substituted by a placebo. |
| Measure Participants | 38 | 38 |
| BEFORE TRAINING |
92.1
(13.6)
|
92.5
(13.6)
|
| AFTER TRAINING |
90.0
(13.2)
|
90.8
(13.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MEDICATED |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.021 |
| Comments | ||
| Method | ANOVA | |
| Comments | REPEATED MEASURES | |
Adverse Events
| Time Frame | 4 months of the intervention | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | No adverse events were recorded | |||
| Arm/Group Title | MEDICATED vs NO MEDICATED BEFORE TRAINING | MEDICATED vs NO MEDICATED AFTER EXERCISE TRAINING | ||
| Arm/Group Description | Subjects will be tested twice one taking their habitual dose of medication, and in the other, the investigators will withhold their medication during 72 h. Untrained, no medicated. Untrained, medicated. | After 4 months of endurance training subjects will be tested twice one taking their habitual dose of medication, and in the other, the investigators will withhold their medication during 72 h. c) Trained, no medicated. d) Trained, medicated. | ||
All Cause Mortality |
||||
| MEDICATED vs NO MEDICATED BEFORE TRAINING | MEDICATED vs NO MEDICATED AFTER EXERCISE TRAINING | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/40 (0%) | 0/40 (0%) | ||
Serious Adverse Events |
||||
| MEDICATED vs NO MEDICATED BEFORE TRAINING | MEDICATED vs NO MEDICATED AFTER EXERCISE TRAINING | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/40 (0%) | 0/40 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| MEDICATED vs NO MEDICATED BEFORE TRAINING | MEDICATED vs NO MEDICATED AFTER EXERCISE TRAINING | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/40 (0%) | 0/40 (0%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Proffessor |
|---|---|
| Organization | University of Castilla-La Mancha |
| Phone | 925268800 |
| ricardo.mora@uclm.es |
Responsible Party:
University of Castilla-La Mancha
ClinicalTrials.gov Identifier:
NCT03019796
Other Study ID Numbers:
- 0112001154 DEP2014-52930-R
First Posted:
Jan 13, 2017
Last Update Posted:
Jun 14, 2021
Last Verified:
May 1, 2021