<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02265107</url>
  </required_header>
  <id_info>
    <org_study_id>PRC-FMD-2014</org_study_id>
    <nct_id>NCT02265107</nct_id>
  </id_info>
  <brief_title>Effects of Exercise Training on Vascular Endothelial Function of Patients Submitted to Coronary Artery Bypass Graft</brief_title>
  <official_title>Effects of Exercise Training on Vascular Endothelial Function of Patients Submitted to Coronary Artery Bypass Graft</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Federal do Rio Grande (FURG)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universidade Federal do Rio Grande (FURG)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Objective: To observe the effects of exercise training on vascular endothelial function in&#xD;
      patients undergoing coronary artery bypass graft (CABG) alone in phase III after six months&#xD;
      of Cardiac rehabilitation programs (CRP).&#xD;
&#xD;
      Methods: the investigators contacted all patients undergoing CABG alone in period of 1 year&#xD;
      to participate in a CRP with duration of six months with three weekly sessions of 1 and half&#xD;
      hour of the duration. All patients underwent biochemical blood tests, muscle strength testing&#xD;
      of one repetition maximum (1-RM test) for upper and lower limbs, 6-minute walk test (6MWT),&#xD;
      and evaluation of endothelial function (using flow-mediated vasodilation).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction The cardiac rehabilitation optimizes a cardiac patient's physical,&#xD;
      psychological, and social functioning, in addition to stabilizing, slowing, or even reversing&#xD;
      the progression of the underlying atherosclerotic processes, thereby reducing morbidity and&#xD;
      mortality. Patients who recently had had a myocardial infarction; or had undergone coronary&#xD;
      artery bypass graft; or who had undergone percutaneous coronary interventions; or who are&#xD;
      heart transplantation candidates or recipients; or have stable chronic heart failure,&#xD;
      peripheral arterial disease with claudication, or other forms of CVD are candidates eligible&#xD;
      for cardiac rehabilitation services ( , ).&#xD;
&#xD;
      Recently, studies randomized clinical trials have reported the efficacy of the exercise&#xD;
      training (ET) independently of format of exercise: aerobic, resistance, or combined exercise&#xD;
      training in patients with coronary artery disease ( , ) and, others studies investigated the&#xD;
      effects of ET on vascular endothelial function in patients with stable coronary artery&#xD;
      disease ( ), ischemic heart disease ( ), recent myocardial infarction (4), and chronic heart&#xD;
      failure (3, , ). ET is associated with an improvement in endothelial function, oxidative&#xD;
      stress, and inflammation. Furthermore, the ET promotes beneficial effects on cardiovascular&#xD;
      outcomes and decreases hospitalizations.&#xD;
&#xD;
      Arterial endothelium function evaluated by flow-mediated vasodilation (FMD) is a predictor of&#xD;
      long-term adverse cardiovascular outcomes in healthy subjects ( ). Vascular endothelial&#xD;
      dysfunction is an independent risk factor for cardiovascular events and provides important&#xD;
      prognostic data in addition to the more traditional risk factors ( ). Endothelial dysfunction&#xD;
      plays an important role in patients with coronary atherosclerosis (both acute and chronic&#xD;
      myocardial ischemia) and heart failure (3,5, ). Therefore, we aim to investigate the effect&#xD;
      of combined exercise training on vascular endothelial function in sedentary patients&#xD;
      submitted to coronary artery bypass graft (CABG) in late phase.&#xD;
&#xD;
      Methods The protocol was approved by the local ethics committee of Associação de Caridade&#xD;
      Santa Casa do Rio Grande Hospital, Rio Grande/RS - Brazil, under the protocol number&#xD;
      003/2013. This study was non-randomized clinical trial. The written informed consent was&#xD;
      obtained from all patients before of the onset of ET. The investigators invited all&#xD;
      consecutive patients submitted to CABG alone at Cardiologic Hospital Doctor Pedro Bertoni of&#xD;
      the Associação de Caridade Santa Casa do Rio Grande in the period of October, 2011 until&#xD;
      October, 2012, who resided in the city of the Rio Grande (RS/Brazil), to participate of the&#xD;
      ET. The investigators excluded the patients that performed others cardiologic procedures with&#xD;
      the CABG. All patients were evaluated by cardiologist, and were ranked in Functional&#xD;
      Classification of New York Heart Association (NYHA) such class I and II. Initially,&#xD;
      twenty-four patients accepted and start to participate of ET, but only nine patients&#xD;
      completed the program until the end.&#xD;
&#xD;
      The program of exercise training (ET) was employed for 6 consecutive months with 3 sessions&#xD;
      per week. The training of physical activity consisted of a combination of aerobic and&#xD;
      resistance exercises for upper and lower limbs. Each session included: (1) 5-minute warm-up,&#xD;
      (2) 30 minutes of aerobic exercise (performed in treadmills and stationary bikes); (3) 20&#xD;
      minutes of resistance exercises with dumbbells for upper limbs and ankle support for lower&#xD;
      limbs (exercises preformed in diagonals) that consisted of 6 sets of 10 resistance exercises&#xD;
      repeated for upper limbs, and the same number of sets for lower limbs; and (4) 5-minute&#xD;
      cool-down, totaling ninety minutes of session per day (90min/day) and, two hundred and&#xD;
      seventy minutes per week (270min/week) ( ). Initialy, in aerobic exercises, the maximal HR to&#xD;
      be achieved was established between 30-40% of HR at rest and, the aerobic exercise was&#xD;
      limited by symptoms reported by patients. The initial weight of the dumbbells and ankle were&#xD;
      established between 30-40% of one-repetition maximum test (1-RM test) and, gradually&#xD;
      increased according to the symptoms reported by patients, without compensation of the trunk&#xD;
      to perform the exercises, no history of muscle pain, and no muscle fatigue to complete all&#xD;
      sessions. Heart rate (HR), respiratory rate (RR), saturation pulse of oxygen, and blood&#xD;
      pressure were measured at the beginning, middle and end of each session. The intensity and&#xD;
      the velocity of the exercise program were progressively increased.&#xD;
&#xD;
      The baseline assessment was performed before the beginning of ET and, consisted of: blood&#xD;
      chemistry (glycemia, insulin, glycohemoglobin, total-, high-, and low-density lipoprotein&#xD;
      cholesterol, triglycerides); body mass index; strength of upper and lower limbs by 1-RM test&#xD;
      of biceps brachialis and quadriceps, respectively; evaluation of functional capacity and;&#xD;
      evaluation of vascular endothelial function.&#xD;
&#xD;
      Cholesterol, triglycerides, high-density lipoproteins (HDLc) and, glucose urea were measured&#xD;
      using LAB TEST commercial kits (Lagoa Santa, MG, Brazil) and analyzed in LAB MAX 240® (Tokyo,&#xD;
      Japan) equipment. The low density lipoproteins (LDLc) was calculated by Friedewald's formula.&#xD;
      Glucose levels were measured by Trinder assay (calorimetry) in the equipment LAB MAX 240®&#xD;
      (Tokyo, Japan). The insulin was assessed by chemiluminescence method using the Immulite® DPC&#xD;
      equipment (Diagnostic Products Corporation - DPC, Los Angeles, CA, USA). The glycosylated&#xD;
      hemoglobin (HbA1c) was determined by enzymatic method using the equipment LAB MAX 240®&#xD;
      (Tokyo, Japan).&#xD;
&#xD;
      The 6-minutes walking test (6MWT) is used to assess the functional capacity of the&#xD;
      individual, which is extremely important to evaluate tolerance and exercise capacities for&#xD;
      the evaluation clinical and prognosis of patients with cardiovascular and pulmonary diseases&#xD;
      ( , ). The 6MWT was performed on the first day in a linear corridor with 40 meters of length,&#xD;
      and the researcher performed the test giving verbal commands to the patient, which should be&#xD;
      done the best speed supported by him, and the researcher asked to the patient what their&#xD;
      physical sensations. Data were collected before, at 3 minutes and at the end of the test for&#xD;
      respiratory rate (RR), heart rate (HR), saturation pulse in portable pulse oximeter (Nonin®,&#xD;
      model 9500, Plymouth, USA), and blood pressure systemic.&#xD;
&#xD;
      Flow-mediated vasodilation (FMD) was measured to evaluating arterial endothelium-dependent&#xD;
      vasodilation using a high-resolution vascular ultrasound (Logiq P6, GE Healtcare, GE&#xD;
      Ultrasound Korea Ltda.) according to American Heart Association Guideline ( ) with&#xD;
      adjustments ( , ). Settings of depth and gain imaging were kept constant throughout the&#xD;
      study. Briefly, changing in brachial artery diameter after 60 s of reactive hyperemia, after&#xD;
      deflation of a cuff placed around the upper arm and inflated to 50 mmHg above the systolic&#xD;
      blood pressure during five min, was compared with a baseline measurement. To evaluate basal&#xD;
      blood flow and flow immediately after cuff release obtained no later than 15 s after cuff&#xD;
      deflation we used a pulsed-wave Doppler velocity signals (assessed using Doppler bean-vessel&#xD;
      angle ≤60º). The increased diameter after a sublingual nitroglycerin spray (0.4 mg) was used&#xD;
      as a measurement of endothelium-independent vasodilation. The vessel diameter responses to&#xD;
      reactive hyperemia and to nitroglycerin were expressed as the percentage changing relative to&#xD;
      diameter immediately before cuff inflation and to diameter immediately before drug&#xD;
      administration. Measurements of brachial artery diameter were accomplished off line by two&#xD;
      evaluators using a semiautomatic quantitative analysis system after interventions. The second&#xD;
      evaluator performing measures was blind to first evaluator's measures. Differences larger&#xD;
      than 0.01 mm between assessors (mean vessel diameter) repeated were repeated. All data were&#xD;
      measured twice, and final values were present as mean.&#xD;
&#xD;
      A nutritional counseling was performed, in wich the patients were instructed to avoid&#xD;
      consumption of saturated fat and high-calorie foodstuff, to intake of dietary fiber, to&#xD;
      maintain good hydration and to implement a fractionation of meals throughout the day, besides&#xD;
      to receive instructions of food preparation, according to &quot;I Diretriz sobre o Consumo de&#xD;
      Gorduras e Saúde Cardiovascular&quot; in &quot;Arquivos Brasileiros de Cardiologia&quot; of the &quot;Sociedade&#xD;
      Brasileira de Cardiologia&quot; ( ).&#xD;
&#xD;
      All tests were repeated after 6 months, and the results were compared to baseline tests. The&#xD;
      training program was stopped at this point.&#xD;
&#xD;
      The data are presented as the means ± SD. Distribution of variables was tested by Shapiro&#xD;
      Wilk normality test. Baseline values were compared to values after 6 months of training&#xD;
      program by use paired t-test. A value of P&lt;0.05 was considered statistically significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Vascular endothelial function</measure>
    <time_frame>after 6 months</time_frame>
  </primary_outcome>
  <other_outcome>
    <measure>6-minute walk test</measure>
    <time_frame>6 months</time_frame>
    <description>The 6-minutes walking test (6MWT) is used to assess the functional capacity of the individual</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Vasodilation</condition>
  <arm_group>
    <arm_group_label>cardiac rehabilitation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>We invited all consecutive patients submitted to CABG alone at Cardiologic Hospital Doctor Pedro Bertoni of the Associação de Caridade Santa Casa do Rio Grande in the period of October, 2011 until October, 2012, who resided in the city of the Rio Grande (RS/Brazil), to participate of the exercise training (ET). All patients were evaluated by cardiologist, and were ranked in Functional Classification of New York Heart Association (NYHA) such class I and II. Initially, twenty-four patients accepted and start to participate of ET, but only nine patients completed the program until the end.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>exercise training</intervention_name>
    <description>The program of exercise training (ET) was employed for 6 consecutive months with 3 sessions per week. The training of physical activity consisted of a combination of aerobic and resistance exercises for upper and lower limbs. Each session included: (1) 5-minute warm-up, (2) 30 minutes of aerobic exercise (performed in treadmills and stationary bikes); (3) 20 minutes of resistance exercises with dumbbells for upper limbs and ankle support for lower limbs (exercises preformed in diagonals) that consisted of 6 sets of 10 resistance exercises repeated for upper limbs, and the same number of sets for lower limbs; and (4) 5-minute cool-down, totaling ninety minutes of session per day (90min/day) and, two hundred and seventy minutes per week (270min/week).</description>
    <arm_group_label>cardiac rehabilitation</arm_group_label>
    <other_name>cardiac rehabilitation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  resided in the city of the Rio Grande (RS/Brazil);&#xD;
&#xD;
          -  age over 18 years-old;&#xD;
&#xD;
          -  evaluation and medical authorization.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  the patients that performed others cardiologic procedures with the Coronary Artery&#xD;
             Bypass Graft&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Priscila Aikawa</name>
      <address>
        <city>Rio Grande</city>
        <state>Rio Grande do Sul</state>
        <zip>96200-320</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <link>
    <url>http://www.scielo.br/scielo.php?script=sci_arttext&amp;pid=S1517-86922014000100055</url>
    <description>Additional reference</description>
  </link>
  <link>
    <url>http://www.physiomics.eu/media/37024/am_j_physiol_heart_circ_physiol_300_h2_h12__2011.pdf</url>
    <description>Additional reference</description>
  </link>
  <link>
    <url>http://publicacoes.cardiol.br/consenso/2013/Diretriz_Gorduras.pdf</url>
    <description>Additional reference</description>
  </link>
  <link>
    <url>http://bmjopen.bmj.com/content/4/5/e005268.full</url>
    <description>Additional reference</description>
  </link>
  <reference>
    <citation>Leon AS, Franklin BA, Costa F, Balady GJ, Berra KA, Stewart KJ, Thompson PD, Williams MA, Lauer MS; American Heart Association; Council on Clinical Cardiology (Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention); Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity); American association of Cardiovascular and Pulmonary Rehabilitation. Cardiac rehabilitation and secondary prevention of coronary heart disease: an American Heart Association scientific statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity), in collaboration with the American association of Cardiovascular and Pulmonary Rehabilitation. Circulation. 2005 Jan 25;111(3):369-76. doi: 10.1161/01.CIR.0000151788.08740.5C. Erratum In: Circulation. 2005 Apr 5;111(13):1717.</citation>
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    <citation>Vuckovic KM, Piano MR, Phillips SA. Effects of exercise interventions on peripheral vascular endothelial vasoreactivity in patients with heart failure with reduced ejection fraction. Heart Lung Circ. 2013 May;22(5):328-40. doi: 10.1016/j.hlc.2012.12.006. Epub 2013 Jan 20.</citation>
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    <citation>Taylor RS, Brown A, Ebrahim S, Jolliffe J, Noorani H, Rees K, Skidmore B, Stone JA, Thompson DR, Oldridge N. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med. 2004 May 15;116(10):682-92. doi: 10.1016/j.amjmed.2004.01.009.</citation>
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    <citation>Luk TH, Dai YL, Siu CW, Yiu KH, Chan HT, Lee SW, Li SW, Fong B, Wong WK, Tam S, Lau CP, Tse HF. Effect of exercise training on vascular endothelial function in patients with stable coronary artery disease: a randomized controlled trial. Eur J Prev Cardiol. 2012 Aug;19(4):830-9. doi: 10.1177/1741826711415679. Epub 2011 Jul 1.</citation>
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  <reference>
    <citation>Morikawa Y, Mizuno Y, Harada E, Katoh D, Kashiwagi Y, Morita S, Yoshimura M, Uemura S, Saito Y, Yasue H. Aerobic interval exercise training in the afternoon reduces attacks of coronary spastic angina in conjunction with improvement in endothelial function, oxidative stress, and inflammation. Coron Artery Dis. 2013 May;24(3):177-82. doi: 10.1097/MCA.0b013e32835cbef5.</citation>
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    <citation>Anagnostakou V, Chatzimichail K, Dimopoulos S, Karatzanos E, Papazachou O, Tasoulis A, Anastasiou-Nana M, Roussos C, Nanas S. Effects of interval cycle training with or without strength training on vascular reactivity in heart failure patients. J Card Fail. 2011 Jul;17(7):585-91. doi: 10.1016/j.cardfail.2011.02.009. Epub 2011 Apr 22.</citation>
    <PMID>21703531</PMID>
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    <citation>Credeur DP, Mariappan N, Francis J, Thomas D, Moraes D, Welsch MA. Vasoreactivity before and after handgrip training in chronic heart failure patients. Atherosclerosis. 2012 Nov;225(1):154-9. doi: 10.1016/j.atherosclerosis.2012.08.013. Epub 2012 Sep 16.</citation>
    <PMID>23010159</PMID>
  </reference>
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    <citation>Shechter M, Shechter A, Koren-Morag N, Feinberg MS, Hiersch L. Usefulness of brachial artery flow-mediated dilation to predict long-term cardiovascular events in subjects without heart disease. Am J Cardiol. 2014 Jan 1;113(1):162-7. doi: 10.1016/j.amjcard.2013.08.051. Epub 2013 Oct 5.</citation>
    <PMID>24169007</PMID>
  </reference>
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    <citation>Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation. 2005 Jan 25;111(3):363-8. doi: 10.1161/01.CIR.0000153339.27064.14. No abstract available.</citation>
    <PMID>15668353</PMID>
  </reference>
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    <citation>Fiorina C, Vizzardi E, Lorusso R, Maggio M, De Cicco G, Nodari S, Faggiano P, Dei Cas L. The 6-min walking test early after cardiac surgery. Reference values and the effects of rehabilitation programme. Eur J Cardiothorac Surg. 2007 Nov;32(5):724-9. doi: 10.1016/j.ejcts.2007.08.013. Epub 2007 Sep 18.</citation>
    <PMID>17881241</PMID>
  </reference>
  <reference>
    <citation>Signori LU, Quadros AS, Sbruzzi G, Dipp T, Lopes RD, Schaan BD. Endothelial function in patients with slow coronary flow and normal coronary angiography. Clinics (Sao Paulo). 2012;67(6):677-80. doi: 10.6061/clinics/2012(06)22. No abstract available.</citation>
    <PMID>22760911</PMID>
  </reference>
  <reference>
    <citation>Lee KW, Blann AD, Jolly K, Lip GY; BRUM Investigators. Plasma haemostatic markers, endothelial function and ambulatory blood pressure changes with home versus hospital cardiac rehabilitation: the Birmingham Rehabilitation Uptake Maximisation Study. Heart. 2006 Dec;92(12):1732-8. doi: 10.1136/hrt.2006.092163. Epub 2006 Jun 28.</citation>
    <PMID>16807272</PMID>
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    <citation>Hambrecht R, Wolf A, Gielen S, Linke A, Hofer J, Erbs S, Schoene N, Schuler G. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med. 2000 Feb 17;342(7):454-60. doi: 10.1056/NEJM200002173420702.</citation>
    <PMID>10675425</PMID>
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    <citation>Gokce N, Vita JA, Bader DS, Sherman DL, Hunter LM, Holbrook M, O'Malley C, Keaney JF Jr, Balady GJ. Effect of exercise on upper and lower extremity endothelial function in patients with coronary artery disease. Am J Cardiol. 2002 Jul 15;90(2):124-7. doi: 10.1016/s0002-9149(02)02433-5.</citation>
    <PMID>12106840</PMID>
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    <citation>Edwards DG, Schofield RS, Lennon SL, Pierce GL, Nichols WW, Braith RW. Effect of exercise training on endothelial function in men with coronary artery disease. Am J Cardiol. 2004 Mar 1;93(5):617-20. doi: 10.1016/j.amjcard.2003.11.032.</citation>
    <PMID>14996592</PMID>
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    <citation>Ades PA. Cardiac rehabilitation and secondary prevention of coronary heart disease. N Engl J Med. 2001 Sep 20;345(12):892-902. doi: 10.1056/NEJMra001529. No abstract available.</citation>
    <PMID>11565523</PMID>
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    <citation>Opasich C, De Feo S, Pinna GD, Furgi G, Pedretti R, Scrutinio D, Tramarin R. Distance walked in the 6-minute test soon after cardiac surgery: toward an efficient use in the individual patient. Chest. 2004 Dec;126(6):1796-801. doi: 10.1378/chest.126.6.1796.</citation>
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    <citation>Opasich C, Pinna GD, Mazza A, Febo O, Riccardi PG, Capomolla S, Cobelli F, Tavazzi L. Reproducibility of the six-minute walking test in patients with chronic congestive heart failure: practical implications. Am J Cardiol. 1998 Jun 15;81(12):1497-500. doi: 10.1016/s0002-9149(98)00218-5.</citation>
    <PMID>9645905</PMID>
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    <citation>Lee DH, Buth KJ, Martin BJ, Yip AM, Hirsch GM. Frail patients are at increased risk for mortality and prolonged institutional care after cardiac surgery. Circulation. 2010 Mar 2;121(8):973-8. doi: 10.1161/CIRCULATIONAHA.108.841437. Epub 2010 Feb 16.</citation>
    <PMID>20159833</PMID>
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    <citation>Kim C, Kim BO, Lim KB, Kim YJ, Park YB. The Effect of Power-walking in Phase 2 Cardiac Rehabilitation Program. Ann Rehabil Med. 2012 Feb;36(1):133-40. doi: 10.5535/arm.2012.36.1.133. Epub 2012 Feb 29.</citation>
    <PMID>22506246</PMID>
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    <citation>Pavy B, Caillon M. [Effects of a cardiac rehabilitation programme in coronary patient according to age]. Ann Cardiol Angeiol (Paris). 2012 Nov;61(5):338-44. doi: 10.1016/j.ancard.2012.08.038. Epub 2012 Aug 30. French.</citation>
    <PMID>23021239</PMID>
  </reference>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>October 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>October 16, 2014</last_update_submitted>
  <last_update_submitted_qc>October 16, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 17, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidade Federal do Rio Grande (FURG)</investigator_affiliation>
    <investigator_full_name>Priscila Aikawa</investigator_full_name>
    <investigator_title>Priscila Aikawa PhD</investigator_title>
  </responsible_party>
  <keyword>endothelial function</keyword>
  <keyword>physical training</keyword>
  <keyword>exercise</keyword>
  <keyword>coronary artery bypass</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02265107
org study id: PRC-FMD-2014
nct id: NCT02265107
lead sponsor: 
has dmc: No
Objective: To observe the effects of exercise training on vascular endothelial function in
      patients undergoing coronary artery bypass graft (CABG) alone in phase III after six months
      of Cardiac rehabilitation programs (CRP).

      Methods: the investigators contacted all patients undergoing CABG alone in period of 1 year
      to participate in a CRP with duration of six months with three weekly sessions of 1 and half
      hour of the duration. All patients underwent biochemical blood tests, muscle strength testing
      of one repetition maximum (1-RM test) for upper and lower limbs, 6-minute walk test (6MWT),
      and evaluation of endothelial function (using flow-mediated vasodilation).
Introduction The cardiac rehabilitation optimizes a cardiac patient's physical,
      psychological, and social functioning, in addition to stabilizing, slowing, or even reversing
      the progression of the underlying atherosclerotic processes, thereby reducing morbidity and
      mortality. Patients who recently had had a myocardial infarction; or had undergone coronary
      artery bypass graft; or who had undergone percutaneous coronary interventions; or who are
      heart transplantation candidates or recipients; or have stable chronic heart failure,
      peripheral arterial disease with claudication, or other forms of CVD are candidates eligible
      for cardiac rehabilitation services ( , ).

      Recently, studies randomized clinical trials have reported the efficacy of the exercise
      training (ET) independently of format of exercise: aerobic, resistance, or combined exercise
      training in patients with coronary artery disease ( , ) and, others studies investigated the
      effects of ET on vascular endothelial function in patients with stable coronary artery
      disease ( ), ischemic heart disease ( ), recent myocardial infarction (4), and chronic heart
      failure (3, , ). ET is associated with an improvement in endothelial function, oxidative
      stress, and inflammation. Furthermore, the ET promotes beneficial effects on cardiovascular
      outcomes and decreases hospitalizations.

      Arterial endothelium function evaluated by flow-mediated vasodilation (FMD) is a predictor of
      long-term adverse cardiovascular outcomes in healthy subjects ( ). Vascular endothelial
      dysfunction is an independent risk factor for cardiovascular events and provides important
      prognostic data in addition to the more traditional risk factors ( ). Endothelial dysfunction
      plays an important role in patients with coronary atherosclerosis (both acute and chronic
      myocardial ischemia) and heart failure (3,5, ). Therefore, we aim to investigate the effect
      of combined exercise training on vascular endothelial function in sedentary patients
      submitted to coronary artery bypass graft (CABG) in late phase.

      Methods The protocol was approved by the local ethics committee of Associação de Caridade
      Santa Casa do Rio Grande Hospital, Rio Grande/RS - Brazil, under the protocol number
      003/2013. This study was non-randomized clinical trial. The written informed consent was
      obtained from all patients before of the onset of ET. The investigators invited all
      consecutive patients submitted to CABG alone at Cardiologic Hospital Doctor Pedro Bertoni of
      the Associação de Caridade Santa Casa do Rio Grande in the period of October, 2011 until
      October, 2012, who resided in the city of the Rio Grande (RS/Brazil), to participate of the
      ET. The investigators excluded the patients that performed others cardiologic procedures with
      the CABG. All patients were evaluated by cardiologist, and were ranked in Functional
      Classification of New York Heart Association (NYHA) such class I and II. Initially,
      twenty-four patients accepted and start to participate of ET, but only nine patients
      completed the program until the end.

      The program of exercise training (ET) was employed for 6 consecutive months with 3 sessions
      per week. The training of physical activity consisted of a combination of aerobic and
      resistance exercises for upper and lower limbs. Each session included: (1) 5-minute warm-up,
      (2) 30 minutes of aerobic exercise (performed in treadmills and stationary bikes); (3) 20
      minutes of resistance exercises with dumbbells for upper limbs and ankle support for lower
      limbs (exercises preformed in diagonals) that consisted of 6 sets of 10 resistance exercises
      repeated for upper limbs, and the same number of sets for lower limbs; and (4) 5-minute
      cool-down, totaling ninety minutes of session per day (90min/day) and, two hundred and
      seventy minutes per week (270min/week) ( ). Initialy, in aerobic exercises, the maximal HR to
      be achieved was established between 30-40% of HR at rest and, the aerobic exercise was
      limited by symptoms reported by patients. The initial weight of the dumbbells and ankle were
      established between 30-40% of one-repetition maximum test (1-RM test) and, gradually
      increased according to the symptoms reported by patients, without compensation of the trunk
      to perform the exercises, no history of muscle pain, and no muscle fatigue to complete all
      sessions. Heart rate (HR), respiratory rate (RR), saturation pulse of oxygen, and blood
      pressure were measured at the beginning, middle and end of each session. The intensity and
      the velocity of the exercise program were progressively increased.

      The baseline assessment was performed before the beginning of ET and, consisted of: blood
      chemistry (glycemia, insulin, glycohemoglobin, total-, high-, and low-density lipoprotein
      cholesterol, triglycerides); body mass index; strength of upper and lower limbs by 1-RM test
      of biceps brachialis and quadriceps, respectively; evaluation of functional capacity and;
      evaluation of vascular endothelial function.

      Cholesterol, triglycerides, high-density lipoproteins (HDLc) and, glucose urea were measured
      using LAB TEST commercial kits (Lagoa Santa, MG, Brazil) and analyzed in LAB MAX 240® (Tokyo,
      Japan) equipment. The low density lipoproteins (LDLc) was calculated by Friedewald's formula.
      Glucose levels were measured by Trinder assay (calorimetry) in the equipment LAB MAX 240®
      (Tokyo, Japan). The insulin was assessed by chemiluminescence method using the Immulite® DPC
      equipment (Diagnostic Products Corporation - DPC, Los Angeles, CA, USA). The glycosylated
      hemoglobin (HbA1c) was determined by enzymatic method using the equipment LAB MAX 240®
      (Tokyo, Japan).

      The 6-minutes walking test (6MWT) is used to assess the functional capacity of the
      individual, which is extremely important to evaluate tolerance and exercise capacities for
      the evaluation clinical and prognosis of patients with cardiovascular and pulmonary diseases
      ( , ). The 6MWT was performed on the first day in a linear corridor with 40 meters of length,
      and the researcher performed the test giving verbal commands to the patient, which should be
      done the best speed supported by him, and the researcher asked to the patient what their
      physical sensations. Data were collected before, at 3 minutes and at the end of the test for
      respiratory rate (RR), heart rate (HR), saturation pulse in portable pulse oximeter (Nonin®,
      model 9500, Plymouth, USA), and blood pressure systemic.

      Flow-mediated vasodilation (FMD) was measured to evaluating arterial endothelium-dependent
      vasodilation using a high-resolution vascular ultrasound (Logiq P6, GE Healtcare, GE
      Ultrasound Korea Ltda.) according to American Heart Association Guideline ( ) with
      adjustments ( , ). Settings of depth and gain imaging were kept constant throughout the
      study. Briefly, changing in brachial artery diameter after 60 s of reactive hyperemia, after
      deflation of a cuff placed around the upper arm and inflated to 50 mmHg above the systolic
      blood pressure during five min, was compared with a baseline measurement. To evaluate basal
      blood flow and flow immediately after cuff release obtained no later than 15 s after cuff
      deflation we used a pulsed-wave Doppler velocity signals (assessed using Doppler bean-vessel
      angle ≤60º). The increased diameter after a sublingual nitroglycerin spray (0.4 mg) was used
      as a measurement of endothelium-independent vasodilation. The vessel diameter responses to
      reactive hyperemia and to nitroglycerin were expressed as the percentage changing relative to
      diameter immediately before cuff inflation and to diameter immediately before drug
      administration. Measurements of brachial artery diameter were accomplished off line by two
      evaluators using a semiautomatic quantitative analysis system after interventions. The second
      evaluator performing measures was blind to first evaluator's measures. Differences larger
      than 0.01 mm between assessors (mean vessel diameter) repeated were repeated. All data were
      measured twice, and final values were present as mean.

      A nutritional counseling was performed, in wich the patients were instructed to avoid
      consumption of saturated fat and high-calorie foodstuff, to intake of dietary fiber, to
      maintain good hydration and to implement a fractionation of meals throughout the day, besides
      to receive instructions of food preparation, according to "I Diretriz sobre o Consumo de
      Gorduras e Saúde Cardiovascular" in "Arquivos Brasileiros de Cardiologia" of the "Sociedade
      Brasileira de Cardiologia" ( ).

      All tests were repeated after 6 months, and the results were compared to baseline tests. The
      training program was stopped at this point.

      The data are presented as the means ± SD. Distribution of variables was tested by Shapiro
      Wilk normality test. Baseline values were compared to values after 6 months of training
      program by use paired t-test. A value of P<0.05 was considered statistically significant.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: Single (Outcomes Assessor)
measure: Vascular endothelial function
time frame: after 6 months
measure: 6-minute walk test
time frame: 6 months
description: The 6-minutes walking test (6MWT) is used to assess the functional capacity of the individual
arm group label: cardiac rehabilitation
arm group type: Experimental
description: We invited all consecutive patients submitted to CABG alone at Cardiologic Hospital Doctor Pedro Bertoni of the Associação de Caridade Santa Casa do Rio Grande in the period of October, 2011 until October, 2012, who resided in the city of the Rio Grande (RS/Brazil), to participate of the exercise training (ET). All patients were evaluated by cardiologist, and were ranked in Functional Classification of New York Heart Association (NYHA) such class I and II. Initially, twenty-four patients accepted and start to participate of ET, but only nine patients completed the program until the end.
intervention type: Other
intervention name: exercise training
description: The program of exercise training (ET) was employed for 6 consecutive months with 3 sessions per week. The training of physical activity consisted of a combination of aerobic and resistance exercises for upper and lower limbs. Each session included: (1) 5-minute warm-up, (2) 30 minutes of aerobic exercise (performed in treadmills and stationary bikes); (3) 20 minutes of resistance exercises with dumbbells for upper limbs and ankle support for lower limbs (exercises preformed in diagonals) that consisted of 6 sets of 10 resistance exercises repeated for upper limbs, and the same number of sets for lower limbs; and (4) 5-minute cool-down, totaling ninety minutes of session per day (90min/day) and, two hundred and seventy minutes per week (270min/week).
arm group label: cardiac rehabilitation
other name: cardiac rehabilitation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Brazil
url: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1517-86922014000100055
description: Additional reference
url: http://www.physiomics.eu/media/37024/am_j_physiol_heart_circ_physiol_300_h2_h12__2011.pdf
description: Additional reference
url: http://publicacoes.cardiol.br/consenso/2013/Diretriz_Gorduras.pdf
description: Additional reference
url: http://bmjopen.bmj.com/content/4/5/e005268.full
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responsible party type: Principal Investigator
investigator affiliation: Universidade Federal do Rio Grande (FURG)
investigator full name: Priscila Aikawa
investigator title: Priscila Aikawa PhD