<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/NCT03019146</url>
  </required_header>
  <id_info>
    <org_study_id>A12092016</org_study_id>
    <nct_id>NCT03019146</nct_id>
  </id_info>
  <brief_title>Exploring Time-efficient Strategies to Improve Fitness for Surgery in Older Adults</brief_title>
  <acronym>eHHH</acronym>
  <official_title>Exploring Time-efficient Strategies to Improve Fitness for Surgery in Older Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Royal College of Surgeons of England</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Dunhill Medical Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Nottingham</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The incidence of conditions requiring surgical intervention increases with age, however there&#xD;
      is a reported decline in the rates of elective surgical procedures in those over 65. This is&#xD;
      associated with older patients being described as &quot;less fit&quot; and more at risk of&#xD;
      postoperative complications, leading to decreased provision of surgical care to those at&#xD;
      need. Exercise interventions have the potential to reverse some of the decline in&#xD;
      cardiovascular fitness associated with aging and improve the elderly's' &quot;fitness for surgery&quot;&#xD;
      and potentially allow increased access to surgical care for those most in need of it.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The percentage of people aged &gt;65 y in the United Kingdom increased from 15% in 1985 to 17%&#xD;
      in 2010, an increase of 1.7 million people. One age-associated physiological change is the&#xD;
      reduction in vascular function that is observed, both at the levels of the large arteries and&#xD;
      the muscle microvasculature. In itself this vascular dysfunction is associated with reduced&#xD;
      aerobic performance. Cardiorespiratory fitness (marked by aerobic performance) has been shown&#xD;
      to be an independent predictor of postoperative mortality, which provides more accurate&#xD;
      prognostic information than age alone. In contrast, physical activity can reverse elements of&#xD;
      pathophysiology associated with these conditions, including vascular dysfunction.&#xD;
      Nonetheless, major roadblocks to exercise as a strategy to combat age-associated vascular&#xD;
      dysfunction and associated conditions exist, namely: i) poor exercise tolerance, ii) &quot;lack of&#xD;
      time&quot;, iii) age-related mobility impairments, and iv) exercise resistance.&#xD;
&#xD;
      The aim of this study is to investigate whether if novel low-volume, time-efficient training&#xD;
      strategies can improve indices of vascular health and cardiorespiratory performance in older&#xD;
      individuals with a view towards improving their fitness for surgery. Numerous studies have&#xD;
      demonstrated that periods of supervised exercise training effectively improve indices of&#xD;
      cardiorespiratory (blood pressure, aerobic capacity and blood lipids and vascular function.&#xD;
      However, the majority of these studies were conducted using high-volume continuous submaximal&#xD;
      aerobic training (e.g. 50-65% VO2max for 30-60 min) or moderate to high volume progressive&#xD;
      weight training. This research group have recently shown the efficacy of a time-efficient&#xD;
      exercise strategy known as HIIT - High Intensity Interval Training, for improving VO2 max and&#xD;
      muscle mass in young individuals with heightened metabolic disease risk and also demonstrated&#xD;
      significant improvements in VO2 max comparable to classic aerobic exercise training using&#xD;
      several different time-efficient HIIT protocols. However, despite the potential benefits of&#xD;
      HIIT, not least its 70-80% reduction in required time-commitment compared to current WHO&#xD;
      guidelines, it does have limitations, particularly for an older population where physical&#xD;
      (mobility/joint) and/or socio-economic (transport/gym access/equipment purchase) barriers may&#xD;
      render it ineffective and/or unachievable.&#xD;
&#xD;
      Alternative interventions for prevention or treatment of age-associated vascular dysfunction&#xD;
      could be provided by isometric handgrip training (IHG) or remote ischaemic pre-conditioning&#xD;
      (RIPC), both of which have a similar low time-commitment compared to HIIT but are less&#xD;
      strenuous, have potential as home-based interventions, and require only inexpensive&#xD;
      equipment. IHG has been demonstrated to improve resting blood pressure in both normotensive&#xD;
      and medicated hypertensive populations to a similar or greater extent as classic aerobic&#xD;
      exercise training. However, the effects of IHG on other vascular (e.g. limb, brain and muscle&#xD;
      microvascular blood flow) or cardio-respiratory parameters (VO2 max, heart rate&#xD;
      (resting/recovery), exercise tolerance) have not been assessed. Similarly, although RIPC has&#xD;
      recently been shown to improve maximal athletic cardio-respiratory performance and vascular&#xD;
      function in young subjects, no work to date has explored the efficacy of chronic RIPC on&#xD;
      indices of health or vascular function in older individuals.&#xD;
&#xD;
      Therefore, the aims of this project are to:&#xD;
&#xD;
      (i) Assess the efficacy of 6 weeks HIT, IHG and RIPC for improving indices of&#xD;
      cardio-respiratory, vascular and metabolic function in older subjects as a means of improving&#xD;
      fitness for surgery.&#xD;
&#xD;
      (ii) Explore the concept of &quot;exercise resistance&quot; in relation to HIT, IHG and RIPC by:&#xD;
&#xD;
        1. Assessing if the same degree of response heterogeneity exists for the three&#xD;
           time-efficient training modes employed in this study as has been reported for classic&#xD;
           resistance and aerobic exercise training&#xD;
&#xD;
        2. Assessing if a &quot;non-responder&quot; for one index (i.e., resting blood pressure or leg blood&#xD;
           flow) is a non-responder for all other indices&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 4, 2017</start_date>
  <completion_date type="Anticipated">August 1, 2019</completion_date>
  <primary_completion_date type="Actual">April 25, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in resting systolic blood pressure</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured in seated position using oscillometry, mean value of 3 recordings, measured according to British Society of Hypertension Guidelines 2013.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in resting diastolic blood pressure</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured using a ramp incremental exercise test on a cycle ergometer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ambulatory blood pressure</measure>
    <time_frame>6 weeks</time_frame>
    <description>Ambulatory blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>V02 Peak</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured using a ramp incremental exercise test on a cycle ergometer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anaerobic threshold</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured using a ramp incremental exercise test on a cycle ergometer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body fat percentage</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured by dual energy X-ray absorptiometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total body lean mass</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured by dual energy X-ray absorptiometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in common femoral artery blood flow</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured by duplex ultrasound on non-dominant leg in response to 6 unilateral leg extensions at 50% 1 repetition maximum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Vastus lateralis microvascular blood flow</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured by contrast enhanced ultrasound on the dominant leg in response to 6 unilateral leg extensions at 50% 1 repetition maximum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Flow-mediated dilatation</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate recovery post exercise</measure>
    <time_frame>6 weeks</time_frame>
    <description>Change in heart rate after exercise from peak over time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure recovery post exercise</measure>
    <time_frame>6 weeks</time_frame>
    <description>Change in blood pressure after exercise from peak over time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under concentration curve for serum Glucose</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured from a 3 hour oral glucose tolerance test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under concentration curve for serum Insulin</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured from a 3 hour oral glucose tolerance test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Matsuda Index of insulin sensitivity</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured from a 3 hour oral glucose tolerance test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cederholm Index of insulin sensitivity</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured from a 3 hour oral glucose tolerance test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Homeostatic Model Assessment of Insulin Resistance</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured from fasting plasma samples, taken before a 3 hour oral glucose tolerance test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting Serum Cholesterol</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting serum triglyceride</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to failure, cycling at 50% maximum power achieved during CPET</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Handgrip maximum voluntary contraction</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measured using a handgrip dynamometer</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Perioperative Hypertension</condition>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>High Intensity Interval Training (HIIT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 x 15 minute sessions per week for 6 weeks. Sessions include 5x intervals of cycling at 110% of Wmax derived from CPET, interspersed with 90s rest periods of unloaded cycling.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Isometric Handgrip (HOLD)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3x 15 minute sessions per week for 6 weeks Sessions include 4x intervals of 2minutes isometric handgrip contraction of dominant arm at 30% Maximal voluntary contraction, interspersed with 2minute rest periods</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Remote Ischaemic Preconditioning (HUG)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3x 15 minute sessions per week for 6 weeks. Sessions include 3x intervals of 3 minutes of arm ischaemia (blood pressure cuff inflated to 200mmHg on dominant arm) interspersed with 3 minute rest periods.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No intervention</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>HIIT</intervention_name>
    <arm_group_label>High Intensity Interval Training (HIIT)</arm_group_label>
    <other_name>High intensity Interval training</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>HOLD</intervention_name>
    <arm_group_label>Isometric Handgrip (HOLD)</arm_group_label>
    <other_name>Isometric exercise</other_name>
    <other_name>Isometric handgrip</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>HUG</intervention_name>
    <arm_group_label>Remote Ischaemic Preconditioning (HUG)</arm_group_label>
    <other_name>Remote ischaemic preconditioning</other_name>
    <other_name>Ischaemic preconditioning</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteer aged 65-85&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • Current participation in a formal exercise regime&#xD;
&#xD;
               -  A BMI &lt; 18 or &gt; 32 kg·m2&#xD;
&#xD;
               -  Active cardiovascular disease:&#xD;
&#xD;
                    -  uncontrolled hypertension (BP &gt; 160/100),&#xD;
&#xD;
                    -  angina,&#xD;
&#xD;
                    -  heart failure (class III/IV),&#xD;
&#xD;
                    -  Significant arrhythmia,&#xD;
&#xD;
                    -  right to left cardiac shunt,&#xD;
&#xD;
                    -  recent cardiac event&#xD;
&#xD;
               -  Taking beta-adrenergic blocking agents,&#xD;
&#xD;
               -  Cerebrovascular disease:&#xD;
&#xD;
                    -  previous stroke,&#xD;
&#xD;
                    -  aneurysm (large vessel or intracranial)&#xD;
&#xD;
                    -  epilepsy&#xD;
&#xD;
               -  Respiratory disease including:&#xD;
&#xD;
                    -  pulmonary hypertension,&#xD;
&#xD;
                    -  Significant COPD,&#xD;
&#xD;
                    -  Uncontrolled asthma,&#xD;
&#xD;
               -  Metabolic disease:&#xD;
&#xD;
                    -  hyper and hypo parathyroidism,&#xD;
&#xD;
                    -  untreated hyper and hypothyroidism,&#xD;
&#xD;
                    -  Cushing's disease,&#xD;
&#xD;
                    -  type 1 or 2 diabetes&#xD;
&#xD;
               -  Active inflammatory bowel or renal disease&#xD;
&#xD;
               -  Malignancy&#xD;
&#xD;
               -  Clotting dysfunction&#xD;
&#xD;
               -  Significant Musculoskeletal or neurological disorders&#xD;
&#xD;
               -  Family history of early (&lt;55y) death from cardiovascular disease&#xD;
&#xD;
               -  Known sensitivity to Sonovue&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University Of Nottingham</name>
      <address>
        <city>Derby</city>
        <zip>DE22 3NE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://webarchive.nationalarchives.gov.uk/20160105160709/http://www.ons.gov.uk/ons/dcp171776_258607.pdf</url>
    <description>Office for National Statistics; Population Ageing in the United Kingdom, its Constituent Countries and the European Union</description>
  </link>
  <reference>
    <citation>LaRocca TJ, Hearon CM Jr, Henson GD, Seals DR. Mitochondrial quality control and age-associated arterial stiffening. Exp Gerontol. 2014 Oct;58:78-82. doi: 10.1016/j.exger.2014.07.008. Epub 2014 Jul 14.</citation>
    <PMID>25034910</PMID>
  </reference>
  <reference>
    <citation>Phillips BE, Atherton PJ, Varadhan K, Limb MC, Wilkinson DJ, Sjoberg KA, Smith K, Williams JP. The effects of resistance exercise training on macro- and micro-circulatory responses to feeding and skeletal muscle protein anabolism in older men. J Physiol. 2015 Jun 15;593(12):2721-34. doi: 10.1113/JP270343. Epub 2015 May 14.</citation>
    <PMID>25867865</PMID>
  </reference>
  <reference>
    <citation>Gonzalez-Alonso J, Calbet JA. Reductions in systemic and skeletal muscle blood flow and oxygen delivery limit maximal aerobic capacity in humans. Circulation. 2003 Feb 18;107(6):824-30. doi: 10.1161/01.cir.0000049746.29175.3f.</citation>
    <PMID>12591751</PMID>
  </reference>
  <reference>
    <citation>Snowden CP, Prentis J, Jacques B, Anderson H, Manas D, Jones D, Trenell M. Cardiorespiratory fitness predicts mortality and hospital length of stay after major elective surgery in older people. Ann Surg. 2013 Jun;257(6):999-1004. doi: 10.1097/SLA.0b013e31828dbac2.</citation>
    <PMID>23665968</PMID>
  </reference>
  <reference>
    <citation>Iwasaki K, Zhang R, Zuckerman JH, Levine BD. Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit? J Appl Physiol (1985). 2003 Oct;95(4):1575-83. doi: 10.1152/japplphysiol.00482.2003. Epub 2003 Jun 27.</citation>
    <PMID>12832429</PMID>
  </reference>
  <reference>
    <citation>Wilmore JH, Green JS, Stanforth PR, Gagnon J, Rankinen T, Leon AS, Rao DC, Skinner JS, Bouchard C. Relationship of changes in maximal and submaximal aerobic fitness to changes in cardiovascular disease and non-insulin-dependent diabetes mellitus risk factors with endurance training: the HERITAGE Family Study. Metabolism. 2001 Nov;50(11):1255-63. doi: 10.1053/meta.2001.27214.</citation>
    <PMID>11699041</PMID>
  </reference>
  <reference>
    <citation>Vollaard NB, Constantin-Teodosiu D, Fredriksson K, Rooyackers O, Jansson E, Greenhaff PL, Timmons JA, Sundberg CJ. Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance. J Appl Physiol (1985). 2009 May;106(5):1479-86. doi: 10.1152/japplphysiol.91453.2008. Epub 2009 Feb 5.</citation>
    <PMID>19196912</PMID>
  </reference>
  <reference>
    <citation>Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, Bales CW, Henes S, Samsa GP, Otvos JD, Kulkarni KR, Slentz CA. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. 2002 Nov 7;347(19):1483-92. doi: 10.1056/NEJMoa020194.</citation>
    <PMID>12421890</PMID>
  </reference>
  <reference>
    <citation>Santos-Parker JR, LaRocca TJ, Seals DR. Aerobic exercise and other healthy lifestyle factors that influence vascular aging. Adv Physiol Educ. 2014 Dec;38(4):296-307. doi: 10.1152/advan.00088.2014.</citation>
    <PMID>25434012</PMID>
  </reference>
  <reference>
    <citation>Seals DR. Edward F. Adolph Distinguished Lecture: The remarkable anti-aging effects of aerobic exercise on systemic arteries. J Appl Physiol (1985). 2014 Sep 1;117(5):425-39. doi: 10.1152/japplphysiol.00362.2014. Epub 2014 May 22.</citation>
    <PMID>24855137</PMID>
  </reference>
  <reference>
    <citation>Kraus WE, Torgan CE, Duscha BD, Norris J, Brown SA, Cobb FR, Bales CW, Annex BH, Samsa GP, Houmard JA, Slentz CA. Studies of a targeted risk reduction intervention through defined exercise (STRRIDE). Med Sci Sports Exerc. 2001 Oct;33(10):1774-84. doi: 10.1097/00005768-200110000-00025.</citation>
    <PMID>11581566</PMID>
  </reference>
  <reference>
    <citation>Church TS, Earnest CP, Skinner JS, Blair SN. Effects of different doses of physical activity on cardiorespiratory fitness among sedentary, overweight or obese postmenopausal women with elevated blood pressure: a randomized controlled trial. JAMA. 2007 May 16;297(19):2081-91. doi: 10.1001/jama.297.19.2081.</citation>
    <PMID>17507344</PMID>
  </reference>
  <reference>
    <citation>Phillips B, Williams J, Atherton P, Smith K, Hildebrandt W, Rankin D, Greenhaff P, Macdonald I, Rennie MJ. Resistance exercise training improves age-related declines in leg vascular conductance and rejuvenates acute leg blood flow responses to feeding and exercise. J Appl Physiol (1985). 2012 Feb;112(3):347-53. doi: 10.1152/japplphysiol.01031.2011. Epub 2011 Oct 13.</citation>
    <PMID>21998269</PMID>
  </reference>
  <reference>
    <citation>Metcalfe RS, Babraj JA, Fawkner SG, Vollaard NB. Towards the minimal amount of exercise for improving metabolic health: beneficial effects of reduced-exertion high-intensity interval training. Eur J Appl Physiol. 2012 Jul;112(7):2767-75. doi: 10.1007/s00421-011-2254-z. Epub 2011 Nov 29.</citation>
    <PMID>22124524</PMID>
  </reference>
  <reference>
    <citation>Garg R, Malhotra V, Kumar A, Dhar U, Tripathi Y. Effect of isometric handgrip exercise training on resting blood pressure in normal healthy adults. J Clin Diagn Res. 2014 Sep;8(9):BC08-10. doi: 10.7860/JCDR/2014/8908.4850. Epub 2014 Sep 20.</citation>
    <PMID>25386422</PMID>
  </reference>
  <reference>
    <citation>Millar PJ, McGowan CL, Cornelissen VA, Araujo CG, Swaine IL. Evidence for the role of isometric exercise training in reducing blood pressure: potential mechanisms and future directions. Sports Med. 2014 Mar;44(3):345-56. doi: 10.1007/s40279-013-0118-x.</citation>
    <PMID>24174307</PMID>
  </reference>
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    <citation>Jean-St-Michel E, Manlhiot C, Li J, Tropak M, Michelsen MM, Schmidt MR, McCrindle BW, Wells GD, Redington AN. Remote preconditioning improves maximal performance in highly trained athletes. Med Sci Sports Exerc. 2011 Jul;43(7):1280-6. doi: 10.1249/MSS.0b013e318206845d.</citation>
    <PMID>21131871</PMID>
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    <citation>Jones H, Hopkins N, Bailey TG, Green DJ, Cable NT, Thijssen DH. Seven-day remote ischemic preconditioning improves local and systemic endothelial function and microcirculation in healthy humans. Am J Hypertens. 2014 Jul;27(7):918-25. doi: 10.1093/ajh/hpu004. Epub 2014 Mar 13.</citation>
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  </reference>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>May 3, 2019</last_update_submitted>
  <last_update_submitted_qc>May 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prehabilitation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03019146
org study id: A12092016
nct id: NCT03019146
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The incidence of conditions requiring surgical intervention increases with age, however there
      is a reported decline in the rates of elective surgical procedures in those over 65. This is
      associated with older patients being described as "less fit" and more at risk of
      postoperative complications, leading to decreased provision of surgical care to those at
      need. Exercise interventions have the potential to reverse some of the decline in
      cardiovascular fitness associated with aging and improve the elderly's' "fitness for surgery"
      and potentially allow increased access to surgical care for those most in need of it.
The percentage of people aged >65 y in the United Kingdom increased from 15% in 1985 to 17%
      in 2010, an increase of 1.7 million people. One age-associated physiological change is the
      reduction in vascular function that is observed, both at the levels of the large arteries and
      the muscle microvasculature. In itself this vascular dysfunction is associated with reduced
      aerobic performance. Cardiorespiratory fitness (marked by aerobic performance) has been shown
      to be an independent predictor of postoperative mortality, which provides more accurate
      prognostic information than age alone. In contrast, physical activity can reverse elements of
      pathophysiology associated with these conditions, including vascular dysfunction.
      Nonetheless, major roadblocks to exercise as a strategy to combat age-associated vascular
      dysfunction and associated conditions exist, namely: i) poor exercise tolerance, ii) "lack of
      time", iii) age-related mobility impairments, and iv) exercise resistance.

      The aim of this study is to investigate whether if novel low-volume, time-efficient training
      strategies can improve indices of vascular health and cardiorespiratory performance in older
      individuals with a view towards improving their fitness for surgery. Numerous studies have
      demonstrated that periods of supervised exercise training effectively improve indices of
      cardiorespiratory (blood pressure, aerobic capacity and blood lipids and vascular function.
      However, the majority of these studies were conducted using high-volume continuous submaximal
      aerobic training (e.g. 50-65% VO2max for 30-60 min) or moderate to high volume progressive
      weight training. This research group have recently shown the efficacy of a time-efficient
      exercise strategy known as HIIT - High Intensity Interval Training, for improving VO2 max and
      muscle mass in young individuals with heightened metabolic disease risk and also demonstrated
      significant improvements in VO2 max comparable to classic aerobic exercise training using
      several different time-efficient HIIT protocols. However, despite the potential benefits of
      HIIT, not least its 70-80% reduction in required time-commitment compared to current WHO
      guidelines, it does have limitations, particularly for an older population where physical
      (mobility/joint) and/or socio-economic (transport/gym access/equipment purchase) barriers may
      render it ineffective and/or unachievable.

      Alternative interventions for prevention or treatment of age-associated vascular dysfunction
      could be provided by isometric handgrip training (IHG) or remote ischaemic pre-conditioning
      (RIPC), both of which have a similar low time-commitment compared to HIIT but are less
      strenuous, have potential as home-based interventions, and require only inexpensive
      equipment. IHG has been demonstrated to improve resting blood pressure in both normotensive
      and medicated hypertensive populations to a similar or greater extent as classic aerobic
      exercise training. However, the effects of IHG on other vascular (e.g. limb, brain and muscle
      microvascular blood flow) or cardio-respiratory parameters (VO2 max, heart rate
      (resting/recovery), exercise tolerance) have not been assessed. Similarly, although RIPC has
      recently been shown to improve maximal athletic cardio-respiratory performance and vascular
      function in young subjects, no work to date has explored the efficacy of chronic RIPC on
      indices of health or vascular function in older individuals.

      Therefore, the aims of this project are to:

      (i) Assess the efficacy of 6 weeks HIT, IHG and RIPC for improving indices of
      cardio-respiratory, vascular and metabolic function in older subjects as a means of improving
      fitness for surgery.

      (ii) Explore the concept of "exercise resistance" in relation to HIT, IHG and RIPC by:

        1. Assessing if the same degree of response heterogeneity exists for the three
           time-efficient training modes employed in this study as has been reported for classic
           resistance and aerobic exercise training

        2. Assessing if a "non-responder" for one index (i.e., resting blood pressure or leg blood
           flow) is a non-responder for all other indices
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in resting systolic blood pressure
time frame: 6 weeks
description: Measured in seated position using oscillometry, mean value of 3 recordings, measured according to British Society of Hypertension Guidelines 2013.
measure: Change in resting diastolic blood pressure
time frame: 6 weeks
description: Measured using a ramp incremental exercise test on a cycle ergometer.
measure: Ambulatory blood pressure
time frame: 6 weeks
description: Ambulatory blood pressure
measure: V02 Peak
time frame: 6 weeks
description: Measured using a ramp incremental exercise test on a cycle ergometer.
measure: Anaerobic threshold
time frame: 6 weeks
description: Measured using a ramp incremental exercise test on a cycle ergometer.
measure: Body fat percentage
time frame: 6 weeks
description: Measured by dual energy X-ray absorptiometry
measure: Total body lean mass
time frame: 6 weeks
description: Measured by dual energy X-ray absorptiometry
measure: Change in common femoral artery blood flow
time frame: 6 weeks
description: Measured by duplex ultrasound on non-dominant leg in response to 6 unilateral leg extensions at 50% 1 repetition maximum
measure: Change in Vastus lateralis microvascular blood flow
time frame: 6 weeks
description: Measured by contrast enhanced ultrasound on the dominant leg in response to 6 unilateral leg extensions at 50% 1 repetition maximum
measure: Flow-mediated dilatation
time frame: 6 weeks
measure: Heart rate recovery post exercise
time frame: 6 weeks
description: Change in heart rate after exercise from peak over time
measure: Blood pressure recovery post exercise
time frame: 6 weeks
description: Change in blood pressure after exercise from peak over time
measure: Area under concentration curve for serum Glucose
time frame: 6 weeks
description: Measured from a 3 hour oral glucose tolerance test
measure: Area under concentration curve for serum Insulin
time frame: 6 weeks
description: Measured from a 3 hour oral glucose tolerance test
measure: Matsuda Index of insulin sensitivity
time frame: 6 weeks
description: Measured from a 3 hour oral glucose tolerance test
measure: Cederholm Index of insulin sensitivity
time frame: 6 weeks
description: Measured from a 3 hour oral glucose tolerance test
measure: Homeostatic Model Assessment of Insulin Resistance
time frame: 6 weeks
description: Measured from fasting plasma samples, taken before a 3 hour oral glucose tolerance test
measure: Fasting Serum Cholesterol
time frame: 6 weeks
measure: Fasting serum triglyceride
time frame: 6 weeks
measure: Time to failure, cycling at 50% maximum power achieved during CPET
time frame: 6 weeks
measure: Handgrip maximum voluntary contraction
time frame: 6 weeks
description: Measured using a handgrip dynamometer
arm group label: High Intensity Interval Training (HIIT)
arm group type: Experimental
description: 3 x 15 minute sessions per week for 6 weeks. Sessions include 5x intervals of cycling at 110% of Wmax derived from CPET, interspersed with 90s rest periods of unloaded cycling.
arm group label: Isometric Handgrip (HOLD)
arm group type: Experimental
description: 3x 15 minute sessions per week for 6 weeks Sessions include 4x intervals of 2minutes isometric handgrip contraction of dominant arm at 30% Maximal voluntary contraction, interspersed with 2minute rest periods
arm group label: Remote Ischaemic Preconditioning (HUG)
arm group type: Experimental
description: 3x 15 minute sessions per week for 6 weeks. Sessions include 3x intervals of 3 minutes of arm ischaemia (blood pressure cuff inflated to 200mmHg on dominant arm) interspersed with 3 minute rest periods.
arm group label: Control
arm group type: No Intervention
description: No intervention
intervention type: Other
intervention name: HIIT
arm group label: High Intensity Interval Training (HIIT)
other name: High intensity Interval training
intervention type: Other
intervention name: HOLD
arm group label: Isometric Handgrip (HOLD)
other name: Isometric exercise
other name: Isometric handgrip
intervention type: Other
intervention name: HUG
arm group label: Remote Ischaemic Preconditioning (HUG)
other name: Remote ischaemic preconditioning
other name: Ischaemic preconditioning
criteria: 
gender: All
minimum age: 65 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
url: http://webarchive.nationalarchives.gov.uk/20160105160709/http://www.ons.gov.uk/ons/dcp171776_258607.pdf
description: Office for National Statistics; Population Ageing in the United Kingdom, its Constituent Countries and the European Union
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responsible party type: Sponsor
mesh term: Hypertension
sharing ipd: No