<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/NCT04448236</url>
  </required_header>
  <id_info>
    <org_study_id>BFR-RE in COPDAE</org_study_id>
    <nct_id>NCT04448236</nct_id>
  </id_info>
  <brief_title>Effect of Blood Flow Restriction Resistance Exercises in COPDAE In-patient Rehabilitation</brief_title>
  <official_title>Effects on Muscle Strength After Blood Flow Restriction Resistance Exercise (BFR-RE) in Early In-patient Rehabilitation of Chronic Obstructive Pulmonary Disease Acute Exacerbation (COPDAE), a Single Blinded, Randomized Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Authority, Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Authority, Hong Kong</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomised controlled trial of the blood flow restriction resistance exercise&#xD;
      (BFR-RE) for early rehabilitation of chronic obstructive pulmonary disease acute exacerbation&#xD;
      (COPDAE) in the Haven of Hope Hospital.&#xD;
&#xD;
      BFR-RE was invented by Dr. Yoshiaki Sato in Japan 40 years ago. This exercise was newly&#xD;
      introduced to the Physiotherapy Department of Haven of Hope Hospital in March, 2020 and not a&#xD;
      routine common training in Hospital Authority. However, currently the &quot;BFR-device&quot; is in its&#xD;
      3rd generation. Under the guidance of a certified physiotherapist, a &quot;low load intensity&quot; can&#xD;
      be used for resistance training to build up muscle mass and strength by applying the device&#xD;
      over the thigh to partially limit the blood flow to the distal limb.&#xD;
&#xD;
      BFR-RE is well studied in athletes, elderlies and patients for rehabilitation after&#xD;
      orthopaedics surgeries. A large amount of literature reveals BFR-RE with &quot;low load intensity&quot;&#xD;
      shows comparable increase of muscle mass as &quot;high load intensity&quot; resistance training and&#xD;
      more increase of muscle strength than those only undergoing &quot;low load intensity&quot; resistance&#xD;
      training.&#xD;
&#xD;
      The objective of this study is to investigate the additional effects of 2-week BFR-RE in&#xD;
      patients with COPDAE on top of the conventional in-patient rehabilitation training. The&#xD;
      primary outcome is effect on localized muscle strength. The secondary outcomes include&#xD;
      mobility function, systemic muscle strength as reflected by handgrip strength(HGS), health&#xD;
      related quality of life, unplanned readmission to acute hospital rate within 1 month for&#xD;
      COPDAE.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic obstructive pulmonary disease (COPD) is a prevalent disease around the world&#xD;
      particularly in developed countries. COPD often has frequent admissions for acute&#xD;
      exacerbation which increase the risks of mortality. Muscular dysfunction is one of&#xD;
      extra-pulmonary morbidity of COPD.&#xD;
&#xD;
      Reduced muscle strength is associated with increased mortality in moderate to severe COPD.&#xD;
      However, at least 70% of 1-repetition maximum (1-RM) of weight is needed to achieve muscle&#xD;
      growth in resistance training. This might not be feasible particularly to the patients&#xD;
      admitted for COPD acute exacerbation (COPDAE).&#xD;
&#xD;
      Blood flow restriction resistance training (BFR-RE), Kaatsu training, was developed by Dr.&#xD;
      Yoshiaki Sato more than 40 years ago. The basic physiological mechanism of BFR-RE to increase&#xD;
      muscle mass and strength is by metabolite accumulation, e.g. lactate. The metabolites lead to&#xD;
      increase of serum growth hormone (GH) which promotes the collagen synthesis for tissue repair&#xD;
      and recovery. The surge of GH leads to release of insulin-like growth factor (IGF-1) which is&#xD;
      a protein related to muscle growth. IGF-1 contributes the muscle gain, which is a muscular&#xD;
      anabolic process, by enhancing satellite cell proliferation.&#xD;
&#xD;
      Concerning growth of muscle mass, BFR-RE leads to a comparable increase when compared to high&#xD;
      load resistance exercise (HL-RE). However, concerning increase of muscle strength, BFR-RE is&#xD;
      less effective in gain than that in HL- RE but more effective than that in low load&#xD;
      resistance exercise (LL-RE) alone. Therefore, BFR-RE can be considered when HL- RE is not&#xD;
      advisable. (e.g. frail elderly, post-operative rehabilitation, etc.) BFR-RE is well studied&#xD;
      among healthy adult, elderly and musculoskeletal rehabilitation patients, but not in COPDAE&#xD;
      patients.&#xD;
&#xD;
      Standardized isotonic knee extension resistance training on alternate day with a load of&#xD;
      15-30% of 1-Repetition Maximum (1-RM) with &quot;BFR-device&quot; will be compared with the control arm&#xD;
      having same set of exercise training without the device in COPDAE patient during 2-week of&#xD;
      inpatient stay. Referred to previous study with 30% drop out rate estimation, 24 patients for&#xD;
      each arm will be needed. Study period will be set to be 9 months or until expected&#xD;
      recruitment achieved.&#xD;
&#xD;
      Though there no adverse risk responses were reported in published randomized controlled&#xD;
      trials in clinical populations in the literature, there are some expected transient&#xD;
      perceptual type responses, e.g. dizziness, limb numbness, perceived exertion, delayed onset&#xD;
      muscle soreness. There are no significant risks of complications if BFR-RE is prescribed by&#xD;
      certified trainers who have knowledge of appropriate protocols and contraindications to the&#xD;
      use of occlusive stimuli.&#xD;
&#xD;
      The effect on muscle strength in COPDAE inpatient, which is not well studied in the&#xD;
      literatures, will be the primary outcome of this study. The effect on mobility functions,&#xD;
      systemic muscle strength, health related quality of life, unplanned readmission rate within 1&#xD;
      month of discharge for COPDAE, acceptability and feasibility of the BFR-RE will be evaluated&#xD;
      as secondary outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 10, 2020</start_date>
  <completion_date type="Anticipated">April 2021</completion_date>
  <primary_completion_date type="Anticipated">March 2021</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>
    <intervention_model_description>Participants are randomized into one of the two treatment groups by drawing enclosed envelops which contain the random allocation of participants to intervention group (training with &quot;BFR-device&quot; and control group (training without the device). The envelopes are opened after inclusion for the individual participant only.&#xD;
Stratification of participants into two groups by maximum voluntary isometric contraction (MVIC) at baseline before randomization will be done. The cutoff for the stratification will be determined from the data in the recent service.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The Assessor for the primary outcome (maximum voluntary isometric contraction, MVIC) of knee extension, functional outcomes(6-minute walk test, Short Physical Performance Battery), will be blinded to the allocated study group.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The change of maximal voluntary isometric contraction (MVIC) of knee extension of the dominant leg</measure>
    <time_frame>through study completion in 3 weeks (after 10-12 sessions of training)</time_frame>
    <description>To measure the change of the force-producing capabilities of a muscle group objectively during its isometric contraction condition which means muscle group under contraction with a constant velocity of joint motion and muscle length.&#xD;
Computer dynamometer will be used to measure the MVIC of the isometric knee extension of the dominant leg.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The change of scores of Short physical performance Battery (SPPB)</measure>
    <time_frame>through study completion in 3 weeks (after 10-12 sessions of training)</time_frame>
    <description>Gait speed with 4m distance, Balance test &amp; repeated chair stands test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change of hand grip strength</measure>
    <time_frame>through study completion in 3 weeks (after 10-12 sessions of training)</time_frame>
    <description>a non-invasive marker of systemic skeletal muscle strength and function, is assessed by handheld grip dynamometer of dominant hand</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change of health related quality of life: Chinese version of COPD assessment test (CAT)</measure>
    <time_frame>through study completion in 3 weeks (after 10-12 sessions of training)</time_frame>
    <description>Self-administered Chinese version of COPD assessment test (CAT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability of Blood flow restriction resistance exercise</measure>
    <time_frame>pain score before, immediate and 5-minute post exercise;</time_frame>
    <description>Measure pain score by visual analog scale (0-10) before, immediate and 5-minute post exercise.&#xD;
least pain=0 ; most severe pain=10</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reasons of drop-out of Blood flow restriction resistance exercise</measure>
    <time_frame>through study completion in 3 weeks (after 10-12 sessions of training)</time_frame>
    <description>Examination the reasons of drop-out in those discontinuing the training</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility of Blood flow restriction resistance exercise</measure>
    <time_frame>through study completion in 3 weeks (after 10-12 sessions of training)</time_frame>
    <description>Examination of drop-out rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned readmission rate within 1 month of discharge for COPDAE</measure>
    <time_frame>1 month after the discharge of patients in the study</time_frame>
    <description>Unplanned readmission rate within 1 month of discharge for COPDAE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6-minute walk test</measure>
    <time_frame>through study completion in 3 weeks (after 10-12 sessions of training)</time_frame>
    <description>6-minute walk test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability of Blood flow restriction resistance exercise</measure>
    <time_frame>Acceptance scale will be assessed immediately after the program after 3 (after 10-12 sessions of training)</time_frame>
    <description>Measure the patient's acceptance by a 5-point categorical scale after the whole program.&#xD;
1=very dislike, 2=dislike,3=no comment, 4= like, 5=very like</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <condition>Acute Exacerbation of COPD</condition>
  <arm_group>
    <arm_group_label>BFR-RE intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The participants will have the standardised 2 week resistance training with &quot;BFR-device&quot; with details as follows:&#xD;
Cuff size: medium&#xD;
Restriction time: 5- 10 mins (stop after finishing 4 sets of training or terminating by Physiotherapists)&#xD;
Applied location: alternate quadriceps in consecutive day&#xD;
Applied pressure: 80% limb occlusion pressure (LOP)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Same standardized 2-week in-patient rehabilitation and same amount of the above-mentioned resistance training without the &quot;BFR device&quot;.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Blood flow restriction resistance exercise</intervention_name>
    <description>Application the &quot;Blood flow restriction device&quot; over the proximal thigh to have 80% of the limb occlusion pressure to accumulate the metabolite generated during knee extension</description>
    <arm_group_label>BFR-RE intervention group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. COPD acute exacerbation (COPDAE) as the primary diagnosis for hospitalization or&#xD;
             transfer to pulmonary wards of the Haven of Hope Hospital&#xD;
&#xD;
          2. Able to walk under supervision&#xD;
&#xD;
          3. Understand instruction in Cantonese and can give informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concomitant acute cardiac event&#xD;
&#xD;
          2. Severe hypertension (BP &gt; 180/100)&#xD;
&#xD;
          3. History of venous thromboembolism&#xD;
&#xD;
          4. History of peripheral vascular disease&#xD;
&#xD;
          5. Absence of posterior tibial or dorsalis pedal pulse&#xD;
&#xD;
          6. History of revascularization of the extremity&#xD;
&#xD;
          7. History of lymphectomies&#xD;
&#xD;
          8. Extremities with dialysis access&#xD;
&#xD;
          9. Vascular grafting&#xD;
&#xD;
         10. Current extremity infection&#xD;
&#xD;
         11. Active malignancy&#xD;
&#xD;
         12. Open fracture / soft tissue injuries&#xD;
&#xD;
         13. Amputation to the lower extremity&#xD;
&#xD;
         14. Expected hospitalization less than 2 weeks on admission&#xD;
&#xD;
         15. Medications known to increase clotting risks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>chung wai LAU, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Authority, Hong Kong</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>chung wai LAU, MBBS</last_name>
    <phone>27038888</phone>
    <phone_ext>852</phone_ext>
    <email>lcw431@ha.org.hk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Haven of Hope Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chung Wai LAU, MBBS</last_name>
      <phone>63837918</phone>
      <email>lcw431@ha.org.hk</email>
    </contact>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
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    <citation>American College of Sports Medicine. American College of Sports Medicine position stand. Progression models in resistance training for healthy adults. Med Sci Sports Exerc. 2009 Mar;41(3):687-708. doi: 10.1249/MSS.0b013e3181915670.</citation>
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    <citation>Brandner, C. R., May, A. K., Clarkson, M. J., &amp; Warmington, S. A. Reported Side-effects and Safety Considerations for the Use of Blood Flow Restriction During Exercise in Practice and Research. Techniques in Orthopaedics. 2018; 33(2), 114-121.</citation>
  </reference>
  <reference>
    <citation>Centner C, Wiegel P, Gollhofer A, Konig D. Effects of Blood Flow Restriction Training on Muscular Strength and Hypertrophy in Older Individuals: A Systematic Review and Meta-Analysis. Sports Med. 2019 Jan;49(1):95-108. doi: 10.1007/s40279-018-0994-1. Erratum In: Sports Med. 2018 Nov 9;:</citation>
    <PMID>30306467</PMID>
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    <citation>Cook SB, LaRoche DP, Villa MR, Barile H, Manini TM. Blood flow restricted resistance training in older adults at risk of mobility limitations. Exp Gerontol. 2017 Dec 1;99:138-145. doi: 10.1016/j.exger.2017.10.004. Epub 2017 Oct 5.</citation>
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    <citation>Hughes L, Paton B, Rosenblatt B, Gissane C, Patterson SD. Blood flow restriction training in clinical musculoskeletal rehabilitation: a systematic review and meta-analysis. Br J Sports Med. 2017 Jul;51(13):1003-1011. doi: 10.1136/bjsports-2016-097071. Epub 2017 Mar 4.</citation>
    <PMID>28259850</PMID>
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    <citation>Manini TM, Clark BC. Blood flow restricted exercise and skeletal muscle health. Exerc Sport Sci Rev. 2009 Apr;37(2):78-85. doi: 10.1097/JES.0b013e31819c2e5c.</citation>
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    <citation>Sato, Y. The history and future of KAATSU Training. International Journal of KAATSU Training Research. 2005; 1(1): 1-5.</citation>
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    <citation>Swallow EB, Reyes D, Hopkinson NS, Man WD, Porcher R, Cetti EJ, Moore AJ, Moxham J, Polkey MI. Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary disease. Thorax. 2007 Feb;62(2):115-20. doi: 10.1136/thx.2006.062026. Epub 2006 Nov 7.</citation>
    <PMID>17090575</PMID>
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    <citation>Van't Hul A, Harlaar J, Gosselink R, Hollander P, Postmus P, Kwakkel G. Quadriceps muscle endurance in patients with chronic obstructive pulmonary disease. Muscle Nerve. 2004 Feb;29(2):267-74. doi: 10.1002/mus.10552.</citation>
    <PMID>14755493</PMID>
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  <reference>
    <citation>Kroemer KH, Marras WS. Towards an objective assessment of the &quot;maximal voluntary contraction&quot; component in routine muscle strength measurements. Eur J Appl Physiol Occup Physiol. 1980;45(1):1-9. doi: 10.1007/BF00421195.</citation>
    <PMID>7191799</PMID>
  </reference>
  <reference>
    <citation>Robles PG, Mathur S, Janaudis-Fereira T, Dolmage TE, Goldstein RS, Brooks D. Measurement of peripheral muscle strength in individuals with chronic obstructive pulmonary disease: a systematic review. J Cardiopulm Rehabil Prev. 2011 Jan-Feb;31(1):11-24. doi: 10.1097/HCR.0b013e3181ebf302.</citation>
    <PMID>20724932</PMID>
  </reference>
  <reference>
    <citation>Bernabeu-Mora R, Medina-Mirapeix F, Llamazares-Herran E, Garcia-Guillamon G, Gimenez-Gimenez LM, Sanchez-Nieto JM. The Short Physical Performance Battery is a discriminative tool for identifying patients with COPD at risk of disability. Int J Chron Obstruct Pulmon Dis. 2015 Dec 3;10:2619-26. doi: 10.2147/COPD.S94377. eCollection 2015. Erratum In: Int J Chron Obstruct Pulmon Dis. 2016;11:623.</citation>
    <PMID>26664110</PMID>
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    <citation>Hicks RW, Denholm B. Implementing AORN recommended practices for care of patients undergoing pneumatic tourniquet-assisted procedures. AORN J. 2013 Oct;98(4):383-93; quiz 394-6. doi: 10.1016/j.aorn.2013.08.004.</citation>
    <PMID>24075334</PMID>
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    <citation>Kearon C, Ageno W, Cannegieter SC, Cosmi B, Geersing GJ, Kyrle PA; Subcommittees on Control of Anticoagulation, and Predictive and Diagnostic Variables in Thrombotic Disease. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost. 2016 Jul;14(7):1480-3. doi: 10.1111/jth.13336. Epub 2016 Jun 7. No abstract available.</citation>
    <PMID>27428935</PMID>
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    <citation>Jeong M, Kang HK, Song P, Park HK, Jung H, Lee SS, Koo HK. Hand grip strength in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2017 Aug 9;12:2385-2390. doi: 10.2147/COPD.S140915. eCollection 2017.</citation>
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    <citation>Kanada Y, Sakurai H, Sugiura Y, Arai T, Koyama S, Tanabe S. Estimation of 1RM for knee extension based on the maximal isometric muscle strength and body composition. J Phys Ther Sci. 2017 Nov;29(11):2013-2017. doi: 10.1589/jpts.29.2013. Epub 2017 Nov 24.</citation>
    <PMID>29200647</PMID>
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    <citation>Loenneke JP, Wilson JM, Marin PJ, Zourdos MC, Bemben MG. Low intensity blood flow restriction training: a meta-analysis. Eur J Appl Physiol. 2012 May;112(5):1849-59. doi: 10.1007/s00421-011-2167-x. Epub 2011 Sep 16.</citation>
    <PMID>21922259</PMID>
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    <citation>van Melick N, Meddeler BM, Hoogeboom TJ, Nijhuis-van der Sanden MWG, van Cingel REH. How to determine leg dominance: The agreement between self-reported and observed performance in healthy adults. PLoS One. 2017 Dec 29;12(12):e0189876. doi: 10.1371/journal.pone.0189876. eCollection 2017.</citation>
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    <citation>Patterson SD, Hughes L, Warmington S, Burr J, Scott BR, Owens J, Abe T, Nielsen JL, Libardi CA, Laurentino G, Neto GR, Brandner C, Martin-Hernandez J, Loenneke J. Blood Flow Restriction Exercise: Considerations of Methodology, Application, and Safety. Front Physiol. 2019 May 15;10:533. doi: 10.3389/fphys.2019.00533. eCollection 2019. Erratum In: Front Physiol. 2019 Oct 22;10:1332.</citation>
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    <citation>Takeichi N, Ishizaka S, Nishiyama M, et al. Prediction of 1 repetition maximum strength from isometric strength using Hand-Held Dynamometer for the knee extenser. Gen Rehabil, 2012; 40: 1005-1009.</citation>
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    <citation>Yu R, Ong S, Cheung O, Leung J, Woo J. Reference Values of Grip Strength, Prevalence of Low Grip Strength, and Factors Affecting Grip Strength Values in Chinese Adults. J Am Med Dir Assoc. 2017 Jun 1;18(6):551.e9-551.e16. doi: 10.1016/j.jamda.2017.03.006. Epub 2017 Apr 29.</citation>
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  <verification_date>July 2020</verification_date>
  <study_first_submitted>June 13, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>July 12, 2020</last_update_submitted>
  <last_update_submitted_qc>July 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Authority, Hong Kong</investigator_affiliation>
    <investigator_full_name>LAU chung wai</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>muscle strength</keyword>
  <keyword>COPDAE</keyword>
  <keyword>BFRRE</keyword>
  <keyword>isometric knee extension</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>December 21, 2021</submitted>
    <returned>January 20, 2022</returned>
    <submitted>May 31, 2022</submitted>
    <returned>March 15, 2023</returned>
    <submitted>March 19, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04448236
org study id: BFR-RE in COPDAE
nct id: NCT04448236
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a randomised controlled trial of the blood flow restriction resistance exercise
      (BFR-RE) for early rehabilitation of chronic obstructive pulmonary disease acute exacerbation
      (COPDAE) in the Haven of Hope Hospital.

      BFR-RE was invented by Dr. Yoshiaki Sato in Japan 40 years ago. This exercise was newly
      introduced to the Physiotherapy Department of Haven of Hope Hospital in March, 2020 and not a
      routine common training in Hospital Authority. However, currently the "BFR-device" is in its
      3rd generation. Under the guidance of a certified physiotherapist, a "low load intensity" can
      be used for resistance training to build up muscle mass and strength by applying the device
      over the thigh to partially limit the blood flow to the distal limb.

      BFR-RE is well studied in athletes, elderlies and patients for rehabilitation after
      orthopaedics surgeries. A large amount of literature reveals BFR-RE with "low load intensity"
      shows comparable increase of muscle mass as "high load intensity" resistance training and
      more increase of muscle strength than those only undergoing "low load intensity" resistance
      training.

      The objective of this study is to investigate the additional effects of 2-week BFR-RE in
      patients with COPDAE on top of the conventional in-patient rehabilitation training. The
      primary outcome is effect on localized muscle strength. The secondary outcomes include
      mobility function, systemic muscle strength as reflected by handgrip strength(HGS), health
      related quality of life, unplanned readmission to acute hospital rate within 1 month for
      COPDAE.
Chronic obstructive pulmonary disease (COPD) is a prevalent disease around the world
      particularly in developed countries. COPD often has frequent admissions for acute
      exacerbation which increase the risks of mortality. Muscular dysfunction is one of
      extra-pulmonary morbidity of COPD.

      Reduced muscle strength is associated with increased mortality in moderate to severe COPD.
      However, at least 70% of 1-repetition maximum (1-RM) of weight is needed to achieve muscle
      growth in resistance training. This might not be feasible particularly to the patients
      admitted for COPD acute exacerbation (COPDAE).

      Blood flow restriction resistance training (BFR-RE), Kaatsu training, was developed by Dr.
      Yoshiaki Sato more than 40 years ago. The basic physiological mechanism of BFR-RE to increase
      muscle mass and strength is by metabolite accumulation, e.g. lactate. The metabolites lead to
      increase of serum growth hormone (GH) which promotes the collagen synthesis for tissue repair
      and recovery. The surge of GH leads to release of insulin-like growth factor (IGF-1) which is
      a protein related to muscle growth. IGF-1 contributes the muscle gain, which is a muscular
      anabolic process, by enhancing satellite cell proliferation.

      Concerning growth of muscle mass, BFR-RE leads to a comparable increase when compared to high
      load resistance exercise (HL-RE). However, concerning increase of muscle strength, BFR-RE is
      less effective in gain than that in HL- RE but more effective than that in low load
      resistance exercise (LL-RE) alone. Therefore, BFR-RE can be considered when HL- RE is not
      advisable. (e.g. frail elderly, post-operative rehabilitation, etc.) BFR-RE is well studied
      among healthy adult, elderly and musculoskeletal rehabilitation patients, but not in COPDAE
      patients.

      Standardized isotonic knee extension resistance training on alternate day with a load of
      15-30% of 1-Repetition Maximum (1-RM) with "BFR-device" will be compared with the control arm
      having same set of exercise training without the device in COPDAE patient during 2-week of
      inpatient stay. Referred to previous study with 30% drop out rate estimation, 24 patients for
      each arm will be needed. Study period will be set to be 9 months or until expected
      recruitment achieved.

      Though there no adverse risk responses were reported in published randomized controlled
      trials in clinical populations in the literature, there are some expected transient
      perceptual type responses, e.g. dizziness, limb numbness, perceived exertion, delayed onset
      muscle soreness. There are no significant risks of complications if BFR-RE is prescribed by
      certified trainers who have knowledge of appropriate protocols and contraindications to the
      use of occlusive stimuli.

      The effect on muscle strength in COPDAE inpatient, which is not well studied in the
      literatures, will be the primary outcome of this study. The effect on mobility functions,
      systemic muscle strength, health related quality of life, unplanned readmission rate within 1
      month of discharge for COPDAE, acceptability and feasibility of the BFR-RE will be evaluated
      as secondary outcomes.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants are randomized into one of the two treatment groups by drawing enclosed envelops which contain the random allocation of participants to intervention group (training with "BFR-device" and control group (training without the device). The envelopes are opened after inclusion for the individual participant only.
Stratification of participants into two groups by maximum voluntary isometric contraction (MVIC) at baseline before randomization will be done. The cutoff for the stratification will be determined from the data in the recent service.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The Assessor for the primary outcome (maximum voluntary isometric contraction, MVIC) of knee extension, functional outcomes(6-minute walk test, Short Physical Performance Battery), will be blinded to the allocated study group.
measure: The change of maximal voluntary isometric contraction (MVIC) of knee extension of the dominant leg
time frame: through study completion in 3 weeks (after 10-12 sessions of training)
description: To measure the change of the force-producing capabilities of a muscle group objectively during its isometric contraction condition which means muscle group under contraction with a constant velocity of joint motion and muscle length.
Computer dynamometer will be used to measure the MVIC of the isometric knee extension of the dominant leg.
measure: The change of scores of Short physical performance Battery (SPPB)
time frame: through study completion in 3 weeks (after 10-12 sessions of training)
description: Gait speed with 4m distance, Balance test & repeated chair stands test
measure: The change of hand grip strength
time frame: through study completion in 3 weeks (after 10-12 sessions of training)
description: a non-invasive marker of systemic skeletal muscle strength and function, is assessed by handheld grip dynamometer of dominant hand
measure: The change of health related quality of life: Chinese version of COPD assessment test (CAT)
time frame: through study completion in 3 weeks (after 10-12 sessions of training)
description: Self-administered Chinese version of COPD assessment test (CAT)
measure: Acceptability of Blood flow restriction resistance exercise
time frame: pain score before, immediate and 5-minute post exercise;
description: Measure pain score by visual analog scale (0-10) before, immediate and 5-minute post exercise.
least pain=0 ; most severe pain=10
measure: Reasons of drop-out of Blood flow restriction resistance exercise
time frame: through study completion in 3 weeks (after 10-12 sessions of training)
description: Examination the reasons of drop-out in those discontinuing the training
measure: Feasibility of Blood flow restriction resistance exercise
time frame: through study completion in 3 weeks (after 10-12 sessions of training)
description: Examination of drop-out rate
measure: Unplanned readmission rate within 1 month of discharge for COPDAE
time frame: 1 month after the discharge of patients in the study
description: Unplanned readmission rate within 1 month of discharge for COPDAE
measure: 6-minute walk test
time frame: through study completion in 3 weeks (after 10-12 sessions of training)
description: 6-minute walk test
measure: Acceptability of Blood flow restriction resistance exercise
time frame: Acceptance scale will be assessed immediately after the program after 3 (after 10-12 sessions of training)
description: Measure the patient's acceptance by a 5-point categorical scale after the whole program.
1=very dislike, 2=dislike,3=no comment, 4= like, 5=very like
arm group label: BFR-RE intervention group
arm group type: Experimental
description: The participants will have the standardised 2 week resistance training with "BFR-device" with details as follows:
Cuff size: medium
Restriction time: 5- 10 mins (stop after finishing 4 sets of training or terminating by Physiotherapists)
Applied location: alternate quadriceps in consecutive day
Applied pressure: 80% limb occlusion pressure (LOP)
arm group label: Control group
arm group type: No Intervention
description: Same standardized 2-week in-patient rehabilitation and same amount of the above-mentioned resistance training without the "BFR device".
intervention type: Device
intervention name: Blood flow restriction resistance exercise
description: Application the "Blood flow restriction device" over the proximal thigh to have 80% of the limb occlusion pressure to accumulate the metabolite generated during knee extension
arm group label: BFR-RE intervention group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: chung wai LAU, MBBS
role: Principal Investigator
affiliation: Hospital Authority, Hong Kong
last name: chung wai LAU, MBBS
phone: 27038888
phone ext: 852
email: lcw431@ha.org.hk
facility: 
status: Recruiting
contact: 
country: Hong Kong
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responsible party type: Principal Investigator
investigator affiliation: Hospital Authority, Hong Kong
investigator full name: LAU chung wai
investigator title: Principal investigator
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: No
submitted: December 21, 2021
returned: January 20, 2022
submitted: May 31, 2022
returned: March 15, 2023
submitted: March 19, 2023