xml: <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/NCT05984823</url>
    </required_header>
    <id_info>
      <org_study_id>HomeBFR-COPD</org_study_id>
      <nct_id>NCT05984823</nct_id>
    </id_info>
    <brief_title>Home-based Body Weight Exercise With Blood Flow Restriction (BFR): Feasibility of a Novel Rehabilitation Intervention in COPD Patients (HomeBFR-COPD)</brief_title>
    <acronym>HomeBFR-COPD</acronym>
    <official_title>Home-based Body Weight Exercise With Blood Flow Restriction (BFR): Feasibility of a Novel Rehabilitation Intervention in COPD Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Mrs Hanoof Aljohani</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University Hospitals, Leicester</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Loughborough University</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        The primary aim of this randomised controlled trial is to investigate the feasibility and&#xD;
        acceptability of low-intensity exercise with blood flow restriction (BFR) in patients with&#xD;
        Chronic Obstructive Pulmonary disease (COPD).&#xD;
  &#xD;
        The investigators will also collect functional and physiological outcome data to explore&#xD;
        potential mechanisms and provide data for a power calculation to be used in a future&#xD;
        randomised controlled trial (RCT) to ensure that subsequent full scale clinical RCT has&#xD;
        maximum reach and benefit.&#xD;
  &#xD;
        The primary experimental hypothesis that underpins these aims is:&#xD;
  &#xD;
        • Low-intensity exercise with BFR is a tolerable, acceptable, and safe exercise modality in&#xD;
        COPD patients.&#xD;
  &#xD;
        40 patients attending clinics at University Hospitals of Leicester (UHL) National Health&#xD;
        Service (NHS) Trust with diagnosed COPD will be randomly allocated to a home-based body&#xD;
        weight exercise intervention either with or without the blood flow restriction (n=20 in each&#xD;
        group). The body weight exercise will consist of five body weight exercises including:&#xD;
        sitting knee extensions, standing knee raise, heel-toe raises, bilateral mini-squat behind a&#xD;
        chair, and chair rise/sit to stand.&#xD;
  &#xD;
        In addition to the pre and post intervention visits, the initial two training sessions for&#xD;
        both groups will be directly supervised in the research centre. These sessions are to ensure&#xD;
        all exercises are performed correctly and safely and the patient become familiar with the&#xD;
        exercises and BFR equipment and mobile application, which provides exercise guidance and&#xD;
        session recording.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Experimental design:&#xD;
  &#xD;
        This is a randomised, controlled, assessor blind, single centre, clinical trial. Outcome&#xD;
        measurements will be assessed at baseline and following the 6-week home-based intervention.&#xD;
  &#xD;
        Participants:&#xD;
  &#xD;
        40 Eligible participants will be identified and approached by their own clinical team at&#xD;
        routine clinical appointments or at the point of referral to pulmonary rehabilitation (PR).&#xD;
        In addition, potential participants who didn't attend PR or are on the waiting list and&#xD;
        individuals who have previously provided written consent to be contacted about future&#xD;
        research studies will be contacted via post. If interested, a researcher will explain the&#xD;
        study and provide the Participant Information Sheet. All participants will be given at least&#xD;
        48 hours to consider taking part and written informed consent will be obtained before any&#xD;
        study procedure.&#xD;
  &#xD;
        Experimental protocol:&#xD;
  &#xD;
        Patients will be randomised (1:1 intervention: control ratio) matched for age and lung&#xD;
        function to a home-based body weight exercise intervention including sitting knee extensions,&#xD;
        standing knee raise, heel-toe raises, bilateral mini-squat behind a chair, and chair rise/sit&#xD;
        to stand either with or without the blood flow restriction (n=20 in each group).&#xD;
  &#xD;
        Baseline outcome measures will be conducted over the first visits to the clinic.&#xD;
  &#xD;
        Initial two training sessions will be directly supervised in the research centre (visits 2 &amp;&#xD;
        3) to ensure all exercises are performed correctly and safely and the patient become familiar&#xD;
        with the trial equipment and related mobile application for exercise guidance and session&#xD;
        recording (digital training). During both sessions, physiological measurements will be made&#xD;
        frequently venous blood samples to assess markers of inflammation, immune and vascular health&#xD;
        will be obtained. A brief survey to assess exercise experience will e completed at the end of&#xD;
        visit 3.&#xD;
  &#xD;
        Patients will then be asked to carry on by performing the same exercises three times per week&#xD;
        at home for the next five weeks. The programme will start at a quite easy level and gradually&#xD;
        increase in intensity every two weeks depending on how the participant gets on. Progression&#xD;
        will incorporate an increase in the number of repetitions and sets every two weeks.&#xD;
  &#xD;
        After the intervention phase, patients will return to the research centre for&#xD;
        post-intervention assessment visit (visit 4) where post-intervention outcome measures&#xD;
        (including a post-training resting blood sample) will be conducted over the same time-course&#xD;
        as the baseline measures. at the end of the visit, a brief survey to assess exercise&#xD;
        experience will be completed. In addition, half of the participants will be interviewed,&#xD;
        within four weeks of completion of the study, to qualitatively assess perceived expectations,&#xD;
        benefits, motives, and barriers to the intervention.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">August 2024</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>Intervention group and control group</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
      <masking_description>For pre and post intervention outcome measures, the assessor will be blinded towards the participants group (Intervention group or control group)</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Recruitment and retention rates</measure>
      <time_frame>Through study completion, an average of 18 months</time_frame>
      <description>The investigators estimate a recruitment rate of 15% with 95% Confidence interval of ± 7%. A recruitment rate of 15% is in line with the referral rate for PR in stable and post-exacerbation COPD.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Retention rates</measure>
      <time_frame>Through study completion, an average of 18 months</time_frame>
      <description>The investigators estimate a retention rate of 80% ± 19%. A retention rate of 80% is close to that seen in pre-pandemic PR programmes locally and is similar to that seen in our previous exercise studies.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Adherence to the intervention (in supervised and unsupervised sessions)</measure>
      <time_frame>Through study completion, an average of 18 months</time_frame>
      <description>The investigators estimate that individuals would complete a mean of 14 out of 18 training sessions (78%, 95% Confidence interval ± 10%).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Safety (adverse events)</measure>
      <time_frame>Through study completion, an average of 18 months</time_frame>
      <description>The investigators will monitor for potential adverse events that may be related to the intervention (venous thromboembolism, rhabdomyolysis, accelerated hypertension, altered lower limb sensation, localised bruising, clotting disorder) through specific screening questionnaires and blood pressure monitoring at study visits. Concerns about possible adverse events will result in direct referral to NHS services for further investigation and involvement in the study will be paused until these investigations have been completed.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Exercise experience</measure>
      <time_frame>Through study completion, an average of 18 months</time_frame>
      <description>Brief survey upon completion of supervised training sessions and upon completion of the study. Survey items build on previous research and relate to exercise experience.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Acceptability</measure>
      <time_frame>Through study completion, an average of 18 months</time_frame>
      <description>Qualitatively with in-depth, semi-structured, one-to-one exit interviews of 50% of participants (randomly chosen) 1 - 4 weeks after completion of the final follow-up assessment.Topics will focus on patients' perceived expectations, benefits, motives, and barriers to the intervention.&#xD;
  - Examining reasons for declining to participate amongst eligible patients, reasons for non-adherence to the exercise intervention, and reasons for dropout amongst discontinuing patients.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Aerobic exercise capacity (VO2peak)</measure>
      <time_frame>At baseline visit (week 0) and follow up visit (week 7).</time_frame>
      <description>VO2peak (ml/kg/min), will be assessed using an incremental-cycle-exercise test on a cycle ergometer which has a high precision for VO2peak confirmation and is well tolerated by patients.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Lower limb function</measure>
      <time_frame>At baseline visit (week 0) and follow up visit (week 7).</time_frame>
      <description>Short Physical Performance Battery (SPPB) will be performed consisting of tests of gait speed, standing balance, and chair stand tests. The SPPB consists of 3 individual sub-tests - standing balance, 4-meter gait speed (4mGS) and 5-repetition sit-to-stand (5STS).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quadriceps muscles strength</measure>
      <time_frame>At baseline visit (week 0) and follow up visit (week 7).</time_frame>
      <description>Maximal isometric and isokinetic quadriceps strength of both legs using an isokinetic dynamometer.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Chronic Respiratory Questionnaire (CRQ)</measure>
      <time_frame>At baseline visit (week 0) and follow up visit (week 7).</time_frame>
      <description>A valuable health related quality of life (HRQL) tool that it incorporates patient perceptions of both physical and emotional health. Four aspects of HRQL are evaluated: dyspnoea, fatigue, emotional function, and mastery. Each domain includes 4 to 7 items, with each item graded on 7-point Likert scale; item scores within a domain are summated to provide a total score for each domain. Higher scores indicate better HRQL.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>COPD Assessment Tool (CAT)</measure>
      <time_frame>At baseline visit (week 0) and follow up visit (week 7).</time_frame>
      <description>CAT questionnaire consists of eight items on a 1-to-5-point scale assessing various manifestations of COPD. It provides a simple quantified measure of health related quality of life (HRQL) focusing on cough, phlegm, chest tightness, breathlessness, limited activities, and confidence leaving home, sleeplessness, and energy. The total score is correlated with the impact level of COPD on health status and is interpreted as low (&lt;10), medium (10-20), high (21-30) and very high (&gt;30).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic response to exercise</measure>
      <time_frame>At visit 2 and 3 (week 1) of supervised training sessions.</time_frame>
      <description>Heart rate (beats per minute) will be monitored throughout exercise using chest strap heart rate sensor (Polar H10)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic response to exercise</measure>
      <time_frame>At visit 2 and 3 (week 1) of supervised training sessions.</time_frame>
      <description>Systolic and diastolic blood pressure (millimetres of mercury) will be continuously assessed during exercise using an ambulatory blood pressure monitor (The Oscar 2™)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic response to exercise</measure>
      <time_frame>At visit 2 and 3 (week 1) of supervised training sessions.</time_frame>
      <description>Oxygen saturations (%O2sat) will be monitored throughout exercise using Nonin 3150 WristOx2 Pulse Oximeter.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Muscle soreness</measure>
      <time_frame>At visit 2 and 3 (week 1) of supervised training sessions.</time_frame>
      <description>Muscle soreness will be assessed using a visual analog scale. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between &quot;no soreness&quot; and &quot;extreme soreness&quot;.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Exercise intensity</measure>
      <time_frame>At visit 2 and 3 (week 1) of supervised training sessions.</time_frame>
      <description>Rate of perceived exertion will be continuously assessed during exercise using Modified Borg Dyspnoea Scale which uses a scale from 0 to 10, where 0 represents no dyspnea and 10 represents maximal dyspnea.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of skeletal muscle damage biomarker (CK)</measure>
      <time_frame>Before, 1 hour after, and 48 hours after exercise at visit 2 of supervised training session (week 1) and at baseline of visit 4 (week 7).</time_frame>
      <description>Venous blood samples will be obtained for measurement of skeletal muscle damage biomarker (CK).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of inflammation biomarkers including, CRP, interleukin-6, immune and endothelial cell-expressed soluble adhesion molecules.</measure>
      <time_frame>Before, 1 hour after, and 48 hours after exercise at visit 2 of supervised training session (week 1) and at baseline of visit 4 (week 7).</time_frame>
      <description>Venous blood samples will be obtained for measurement of inflammation biomarkers (CRP, interleukin-6, immune and endothelial cell-expressed soluble adhesion molecules).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of endothelial function biomarker (bradykinin).</measure>
      <time_frame>Before, 1 hour after, and 48 hours after exercise at visit 2 of supervised training session (week 1) and at baseline of visit 4 (week 7).</time_frame>
      <description>Venous blood samples will be obtained for measurement of endothelial function biomarker (bradykinin).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of cardiac cell injury and stretch biomarkers troponin I and BNP</measure>
      <time_frame>Before, 1 hour after, and 48 hours after exercise at visit 2 of supervised training session (week 1) and at baseline of visit 4 (week 7).</time_frame>
      <description>Venous blood samples will be obtained for measurement of cardiac cell injury and stretch biomarkers (troponin I and BNP).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The presence of endothelial progenitor cells</measure>
      <time_frame>Before, 1 hour after, and 48 hours after exercise at visit 2 of supervised training session (week 1) and at baseline of visit 4 (week 7).</time_frame>
      <description>Venous blood samples will be obtained for measurement of the presence of endothelial progenitor cells.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Chronic Obstructive Pulmonary Disease</condition>
    <arm_group>
      <arm_group_label>Intervention group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Body weight exercise with blood flow restriction</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Exercise only group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Body weight exercise only</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Home based body weight type exercises with blood flow restriction</intervention_name>
      <description>The participant will be asked to complete blood flow restricted exercises described below three times per week for 6 weeks.&#xD;
  Exercise protocol: Two tourniquets will be placed around the upper part of each thigh, these tourniquets will be inflated to an individualised and maintained for the duration of each exercise (including the inter-set rest period) but deflated during the 5 min rest in between. Five Body weight Exercises will be performed: Sitting knee extensions, standing knee raise, Heel-toe raises, Bilateral, mini-squat behind a chair, and Chair rise/sit to stand.</description>
      <arm_group_label>Intervention group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Home based body weight type exercises</intervention_name>
      <description>The participant will be asked to complete body weight exercises for three times per week for 6 weeks. These exercises include: Sitting knee extensions, standing knee raise, Heel-toe raises, Bilateral, mini-squat behind a chair, and Chair rise/sit to stand.</description>
      <arm_group_label>Exercise only group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male or Female&#xD;
  &#xD;
            -  Aged 40 years or above&#xD;
  &#xD;
            -  Diagnosed with COPD as per GOLD criteria (Forced expiratory volume(FEV1)/forced vital&#xD;
               capacity(FVC) &lt;0.7)&#xD;
  &#xD;
            -  FEV1 ≤ 80% predicted&#xD;
  &#xD;
            -  Medical Research Council (MRC) dyspnoea scale ≥2&#xD;
  &#xD;
            -  BMI&lt;30&#xD;
  &#xD;
            -  Willing and able to give informed consent for participation in the study.&#xD;
  &#xD;
            -  Stable dose of current regular medication for at least 4 weeks prior to study entry.&#xD;
  &#xD;
            -  Clinically acceptable ECG at enrolment.&#xD;
  &#xD;
            -  Able (in the investigators opinion) and willing to comply with all study requirements.&#xD;
  &#xD;
            -  Willing to allow his or her General Practitioner and consultant, if appropriate, to be&#xD;
               notified of participation in the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Unable to communicate sufficiently in English&#xD;
  &#xD;
            -  Unable to give informed consent or comply with testing and training protocol for any&#xD;
               reason.&#xD;
  &#xD;
            -  Acute exacerbation in the preceding 4 weeks (would become eligible 4 weeks following&#xD;
               recovery).&#xD;
  &#xD;
            -  Unable to undertake exercise due to physical or psychological barriers.&#xD;
  &#xD;
            -  Contraindication to exercise training (American College of Sports Medicine guidelines)&#xD;
  &#xD;
            -  Any major or uncontrolled comorbidity that would impair the participant's ability to&#xD;
               exercise or would mean exercise was unsafe (e.g., uncontrolled diabetes, hypertension&#xD;
               BP&gt;160/100, muscle or joint injuries which would limit ability to exercise).&#xD;
  &#xD;
            -  Any other significant disease, disorder, or medical condition which, in the opinion of&#xD;
               the Investigator, may either put the participants at risk because of participation in&#xD;
               the study, or may influence the result of the study, or the participant's ability to&#xD;
               participate in the study including (but not limited to):&#xD;
  &#xD;
          Any clotting disorder Any bleeding disorder (e.g., haemophilia) Recent (&lt;3 months) venous&#xD;
          thromboembolism, vascular (artery or vein) surgery to the legs, skin graft to the legs, and&#xD;
          or arteriovenous fistula in the legs.&#xD;
  &#xD;
          Had one or both legs immobilisation in the last 4 weeks (e.g., prolonged bed rest, or&#xD;
          recent orthopaedic intervention) Taking any anticoagulant medication Significant peripheral&#xD;
          neuropathy&#xD;
  &#xD;
            -  Current or within the last 3 months (or maximum relevant wash out period, whichever is&#xD;
               longer), participation in an investigational medicinal product (IMP) or device trial&#xD;
               at the time of screening.&#xD;
  &#xD;
            -  Current or within the last 6 months (or maximum relevant wash out period, whichever is&#xD;
               longer), participation in pulmonary rehabilitation or in another research study&#xD;
               involving exercise training.&#xD;
  &#xD;
            -  Scheduled elective surgery or other procedures requiring general anaesthesia during&#xD;
               the study.&#xD;
  &#xD;
            -  Female participants who are pregnant, lactating, or planning pregnancy during the&#xD;
               course of the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Thomas Ward, MBBS, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University Hospitals, Leicester</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Hanoof A Aljohani, MSc</last_name>
      <phone>+447498721896</phone>
      <email>H.aljohani@lboro.ac.uk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Thomas Ward, MBBS, PhD</last_name>
      <phone>01162583370</phone>
      <email>Tom.Ward@leicester.ac.uk</email>
    </overall_contact_backup>
    <reference>
      <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>
    </reference>
    <reference>
      <citation>Clarkson MJ, Conway L, Warmington SA. Blood flow restriction walking and physical function in older adults: A randomized control trial. J Sci Med Sport. 2017 Dec;20(12):1041-1046. doi: 10.1016/j.jsams.2017.04.012. Epub 2017 Apr 21.</citation>
      <PMID>28483555</PMID>
    </reference>
    <reference>
      <citation>Patterson SD, Hughes L, Head P, Warmington S, Brandner C. Blood flow restriction training: a novel approach to augment clinical rehabilitation: how to do it. Br J Sports Med. 2017 Dec;51(23):1648-1649. doi: 10.1136/bjsports-2017-097738. Epub 2017 Jun 22. No abstract available.</citation>
      <PMID>28642225</PMID>
    </reference>
    <reference>
      <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>
      <PMID>31156448</PMID>
    </reference>
    <reference>
      <citation>Pereira-Neto EA, Johnston KN, Lewthwaite H, Boyle T, Fon A, Williams MT. Title: Blood flow restricted exercise training: Perspectives of people with chronic obstructive pulmonary disease and health professionals. Chron Respir Dis. 2021 Jan-Dec;18:14799731211056092. doi: 10.1177/14799731211056092.</citation>
      <PMID>34823382</PMID>
    </reference>
    <reference>
      <citation>Maltais F, Decramer M, Casaburi R, Barreiro E, Burelle Y, Debigare R, Dekhuijzen PN, Franssen F, Gayan-Ramirez G, Gea J, Gosker HR, Gosselink R, Hayot M, Hussain SN, Janssens W, Polkey MI, Roca J, Saey D, Schols AM, Spruit MA, Steiner M, Taivassalo T, Troosters T, Vogiatzis I, Wagner PD; ATS/ERS Ad Hoc Committee on Limb Muscle Dysfunction in COPD. An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014 May 1;189(9):e15-62. doi: 10.1164/rccm.201402-0373ST.</citation>
      <PMID>24787074</PMID>
    </reference>
    <reference>
      <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>
    </reference>
    <reference>
      <citation>Madarame H, Kurano M, Fukumura K, Fukuda T, Nakajima T. Haemostatic and inflammatory responses to blood flow-restricted exercise in patients with ischaemic heart disease: a pilot study. Clin Physiol Funct Imaging. 2013 Jan;33(1):11-7. doi: 10.1111/j.1475-097X.2012.01158.x. Epub 2012 Jul 30.</citation>
      <PMID>23216760</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 13, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 2, 2023</last_update_submitted>
    <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Loughborough University</investigator_affiliation>
      <investigator_full_name>Mrs Hanoof Aljohani</investigator_full_name>
      <investigator_title>Lead Investigator</investigator_title>
    </responsible_party>
    <keyword>Chronic obstructive pulmonary disease</keyword>
    <keyword>Blood flow restriction</keyword>
    <keyword>Home-based exercise</keyword>
    <keyword>Tele-health</keyword>
    <keyword>Body weight strength exercise</keyword>
    <keyword>Feasibility</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>
      <mesh_term>Body Weight</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>All individual patient data (IPD) that underlie results in a publication</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>Data requests can be submitted starting 6 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.</ipd_time_frame>
      <ipd_access_criteria>Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of research chief investigator and/or principal investigator.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05984823
  org study id: HomeBFR-COPD
  nct id: NCT05984823
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The primary aim of this randomised controlled trial is to investigate the feasibility and
        acceptability of low-intensity exercise with blood flow restriction (BFR) in patients with
        Chronic Obstructive Pulmonary disease (COPD).
  
        The investigators will also collect functional and physiological outcome data to explore
        potential mechanisms and provide data for a power calculation to be used in a future
        randomised controlled trial (RCT) to ensure that subsequent full scale clinical RCT has
        maximum reach and benefit.
  
        The primary experimental hypothesis that underpins these aims is:
  
        • Low-intensity exercise with BFR is a tolerable, acceptable, and safe exercise modality in
        COPD patients.
  
        40 patients attending clinics at University Hospitals of Leicester (UHL) National Health
        Service (NHS) Trust with diagnosed COPD will be randomly allocated to a home-based body
        weight exercise intervention either with or without the blood flow restriction (n=20 in each
        group). The body weight exercise will consist of five body weight exercises including:
        sitting knee extensions, standing knee raise, heel-toe raises, bilateral mini-squat behind a
        chair, and chair rise/sit to stand.
  
        In addition to the pre and post intervention visits, the initial two training sessions for
        both groups will be directly supervised in the research centre. These sessions are to ensure
        all exercises are performed correctly and safely and the patient become familiar with the
        exercises and BFR equipment and mobile application, which provides exercise guidance and
        session recording.
  Experimental design:
  
        This is a randomised, controlled, assessor blind, single centre, clinical trial. Outcome
        measurements will be assessed at baseline and following the 6-week home-based intervention.
  
        Participants:
  
        40 Eligible participants will be identified and approached by their own clinical team at
        routine clinical appointments or at the point of referral to pulmonary rehabilitation (PR).
        In addition, potential participants who didn't attend PR or are on the waiting list and
        individuals who have previously provided written consent to be contacted about future
        research studies will be contacted via post. If interested, a researcher will explain the
        study and provide the Participant Information Sheet. All participants will be given at least
        48 hours to consider taking part and written informed consent will be obtained before any
        study procedure.
  
        Experimental protocol:
  
        Patients will be randomised (1:1 intervention: control ratio) matched for age and lung
        function to a home-based body weight exercise intervention including sitting knee extensions,
        standing knee raise, heel-toe raises, bilateral mini-squat behind a chair, and chair rise/sit
        to stand either with or without the blood flow restriction (n=20 in each group).
  
        Baseline outcome measures will be conducted over the first visits to the clinic.
  
        Initial two training sessions will be directly supervised in the research centre (visits 2 &
        3) to ensure all exercises are performed correctly and safely and the patient become familiar
        with the trial equipment and related mobile application for exercise guidance and session
        recording (digital training). During both sessions, physiological measurements will be made
        frequently venous blood samples to assess markers of inflammation, immune and vascular health
        will be obtained. A brief survey to assess exercise experience will e completed at the end of
        visit 3.
  
        Patients will then be asked to carry on by performing the same exercises three times per week
        at home for the next five weeks. The programme will start at a quite easy level and gradually
        increase in intensity every two weeks depending on how the participant gets on. Progression
        will incorporate an increase in the number of repetitions and sets every two weeks.
  
        After the intervention phase, patients will return to the research centre for
        post-intervention assessment visit (visit 4) where post-intervention outcome measures
        (including a post-training resting blood sample) will be conducted over the same time-course
        as the baseline measures. at the end of the visit, a brief survey to assess exercise
        experience will be completed. In addition, half of the participants will be interviewed,
        within four weeks of completion of the study, to qualitatively assess perceived expectations,
        benefits, motives, and barriers to the intervention.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Intervention group and control group
  primary purpose: Basic Science
  masking: Single (Outcomes Assessor)
  masking description: For pre and post intervention outcome measures, the assessor will be blinded towards the participants group (Intervention group or control group)
  measure: Recruitment and retention rates
  time frame: Through study completion, an average of 18 months
  description: The investigators estimate a recruitment rate of 15% with 95% Confidence interval of ± 7%. A recruitment rate of 15% is in line with the referral rate for PR in stable and post-exacerbation COPD.
  measure: Retention rates
  time frame: Through study completion, an average of 18 months
  description: The investigators estimate a retention rate of 80% ± 19%. A retention rate of 80% is close to that seen in pre-pandemic PR programmes locally and is similar to that seen in our previous exercise studies.
  measure: Adherence to the intervention (in supervised and unsupervised sessions)
  time frame: Through study completion, an average of 18 months
  description: The investigators estimate that individuals would complete a mean of 14 out of 18 training sessions (78%, 95% Confidence interval ± 10%).
  measure: Safety (adverse events)
  time frame: Through study completion, an average of 18 months
  description: The investigators will monitor for potential adverse events that may be related to the intervention (venous thromboembolism, rhabdomyolysis, accelerated hypertension, altered lower limb sensation, localised bruising, clotting disorder) through specific screening questionnaires and blood pressure monitoring at study visits. Concerns about possible adverse events will result in direct referral to NHS services for further investigation and involvement in the study will be paused until these investigations have been completed.
  measure: Exercise experience
  time frame: Through study completion, an average of 18 months
  description: Brief survey upon completion of supervised training sessions and upon completion of the study. Survey items build on previous research and relate to exercise experience.
  measure: Acceptability
  time frame: Through study completion, an average of 18 months
  description: Qualitatively with in-depth, semi-structured, one-to-one exit interviews of 50% of participants (randomly chosen) 1 - 4 weeks after completion of the final follow-up assessment.Topics will focus on patients' perceived expectations, benefits, motives, and barriers to the intervention.
  - Examining reasons for declining to participate amongst eligible patients, reasons for non-adherence to the exercise intervention, and reasons for dropout amongst discontinuing patients.
  measure: Aerobic exercise capacity (VO2peak)
  time frame: At baseline visit (week 0) and follow up visit (week 7).
  description: VO2peak (ml/kg/min), will be assessed using an incremental-cycle-exercise test on a cycle ergometer which has a high precision for VO2peak confirmation and is well tolerated by patients.
  measure: Lower limb function
  time frame: At baseline visit (week 0) and follow up visit (week 7).
  description: Short Physical Performance Battery (SPPB) will be performed consisting of tests of gait speed, standing balance, and chair stand tests. The SPPB consists of 3 individual sub-tests - standing balance, 4-meter gait speed (4mGS) and 5-repetition sit-to-stand (5STS).
  measure: Quadriceps muscles strength
  time frame: At baseline visit (week 0) and follow up visit (week 7).
  description: Maximal isometric and isokinetic quadriceps strength of both legs using an isokinetic dynamometer.
  measure: Chronic Respiratory Questionnaire (CRQ)
  time frame: At baseline visit (week 0) and follow up visit (week 7).
  description: A valuable health related quality of life (HRQL) tool that it incorporates patient perceptions of both physical and emotional health. Four aspects of HRQL are evaluated: dyspnoea, fatigue, emotional function, and mastery. Each domain includes 4 to 7 items, with each item graded on 7-point Likert scale; item scores within a domain are summated to provide a total score for each domain. Higher scores indicate better HRQL.
  measure: COPD Assessment Tool (CAT)
  time frame: At baseline visit (week 0) and follow up visit (week 7).
  description: CAT questionnaire consists of eight items on a 1-to-5-point scale assessing various manifestations of COPD. It provides a simple quantified measure of health related quality of life (HRQL) focusing on cough, phlegm, chest tightness, breathlessness, limited activities, and confidence leaving home, sleeplessness, and energy. The total score is correlated with the impact level of COPD on health status and is interpreted as low (<10), medium (10-20), high (21-30) and very high (>30).
  measure: Hemodynamic response to exercise
  time frame: At visit 2 and 3 (week 1) of supervised training sessions.
  description: Heart rate (beats per minute) will be monitored throughout exercise using chest strap heart rate sensor (Polar H10)
  measure: Hemodynamic response to exercise
  time frame: At visit 2 and 3 (week 1) of supervised training sessions.
  description: Systolic and diastolic blood pressure (millimetres of mercury) will be continuously assessed during exercise using an ambulatory blood pressure monitor (The Oscar 2™)
  measure: Hemodynamic response to exercise
  time frame: At visit 2 and 3 (week 1) of supervised training sessions.
  description: Oxygen saturations (%O2sat) will be monitored throughout exercise using Nonin 3150 WristOx2 Pulse Oximeter.
  measure: Muscle soreness
  time frame: At visit 2 and 3 (week 1) of supervised training sessions.
  description: Muscle soreness will be assessed using a visual analog scale. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no soreness" and "extreme soreness".
  measure: Exercise intensity
  time frame: At visit 2 and 3 (week 1) of supervised training sessions.
  description: Rate of perceived exertion will be continuously assessed during exercise using Modified Borg Dyspnoea Scale which uses a scale from 0 to 10, where 0 represents no dyspnea and 10 represents maximal dyspnea.
  measure: Concentration of skeletal muscle damage biomarker (CK)
  time frame: Before, 1 hour after, and 48 hours after exercise at visit 2 of supervised training session (week 1) and at baseline of visit 4 (week 7).
  description: Venous blood samples will be obtained for measurement of skeletal muscle damage biomarker (CK).
  measure: Concentration of inflammation biomarkers including, CRP, interleukin-6, immune and endothelial cell-expressed soluble adhesion molecules.
  time frame: Before, 1 hour after, and 48 hours after exercise at visit 2 of supervised training session (week 1) and at baseline of visit 4 (week 7).
  description: Venous blood samples will be obtained for measurement of inflammation biomarkers (CRP, interleukin-6, immune and endothelial cell-expressed soluble adhesion molecules).
  measure: Concentration of endothelial function biomarker (bradykinin).
  time frame: Before, 1 hour after, and 48 hours after exercise at visit 2 of supervised training session (week 1) and at baseline of visit 4 (week 7).
  description: Venous blood samples will be obtained for measurement of endothelial function biomarker (bradykinin).
  measure: Concentration of cardiac cell injury and stretch biomarkers troponin I and BNP
  time frame: Before, 1 hour after, and 48 hours after exercise at visit 2 of supervised training session (week 1) and at baseline of visit 4 (week 7).
  description: Venous blood samples will be obtained for measurement of cardiac cell injury and stretch biomarkers (troponin I and BNP).
  measure: The presence of endothelial progenitor cells
  time frame: Before, 1 hour after, and 48 hours after exercise at visit 2 of supervised training session (week 1) and at baseline of visit 4 (week 7).
  description: Venous blood samples will be obtained for measurement of the presence of endothelial progenitor cells.
  arm group label: Intervention group
  arm group type: Experimental
  description: Body weight exercise with blood flow restriction
  arm group label: Exercise only group
  arm group type: Active Comparator
  description: Body weight exercise only
  intervention type: Other
  intervention name: Home based body weight type exercises with blood flow restriction
  description: The participant will be asked to complete blood flow restricted exercises described below three times per week for 6 weeks.
  Exercise protocol: Two tourniquets will be placed around the upper part of each thigh, these tourniquets will be inflated to an individualised and maintained for the duration of each exercise (including the inter-set rest period) but deflated during the 5 min rest in between. Five Body weight Exercises will be performed: Sitting knee extensions, standing knee raise, Heel-toe raises, Bilateral, mini-squat behind a chair, and Chair rise/sit to stand.
  arm group label: Intervention group
  intervention type: Other
  intervention name: Home based body weight type exercises
  description: The participant will be asked to complete body weight exercises for three times per week for 6 weeks. These exercises include: Sitting knee extensions, standing knee raise, Heel-toe raises, Bilateral, mini-squat behind a chair, and Chair rise/sit to stand.
  arm group label: Exercise only group
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Thomas Ward, MBBS, PhD
  role: Principal Investigator
  affiliation: University Hospitals, Leicester
  last name: Hanoof A Aljohani, MSc
  phone: +447498721896
  email: H.aljohani@lboro.ac.uk
  last name: Thomas Ward, MBBS, PhD
  phone: 01162583370
  email: Tom.Ward@leicester.ac.uk
  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.
  PMID: 28259850
  citation: Clarkson MJ, Conway L, Warmington SA. Blood flow restriction walking and physical function in older adults: A randomized control trial. J Sci Med Sport. 2017 Dec;20(12):1041-1046. doi: 10.1016/j.jsams.2017.04.012. Epub 2017 Apr 21.
  PMID: 28483555
  citation: Patterson SD, Hughes L, Head P, Warmington S, Brandner C. Blood flow restriction training: a novel approach to augment clinical rehabilitation: how to do it. Br J Sports Med. 2017 Dec;51(23):1648-1649. doi: 10.1136/bjsports-2017-097738. Epub 2017 Jun 22. No abstract available.
  PMID: 28642225
  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.
  PMID: 31156448
  citation: Pereira-Neto EA, Johnston KN, Lewthwaite H, Boyle T, Fon A, Williams MT. Title: Blood flow restricted exercise training: Perspectives of people with chronic obstructive pulmonary disease and health professionals. Chron Respir Dis. 2021 Jan-Dec;18:14799731211056092. doi: 10.1177/14799731211056092.
  PMID: 34823382
  citation: Maltais F, Decramer M, Casaburi R, Barreiro E, Burelle Y, Debigare R, Dekhuijzen PN, Franssen F, Gayan-Ramirez G, Gea J, Gosker HR, Gosselink R, Hayot M, Hussain SN, Janssens W, Polkey MI, Roca J, Saey D, Schols AM, Spruit MA, Steiner M, Taivassalo T, Troosters T, Vogiatzis I, Wagner PD; ATS/ERS Ad Hoc Committee on Limb Muscle Dysfunction in COPD. An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014 May 1;189(9):e15-62. doi: 10.1164/rccm.201402-0373ST.
  PMID: 24787074
  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.
  PMID: 17090575
  citation: Madarame H, Kurano M, Fukumura K, Fukuda T, Nakajima T. Haemostatic and inflammatory responses to blood flow-restricted exercise in patients with ischaemic heart disease: a pilot study. Clin Physiol Funct Imaging. 2013 Jan;33(1):11-7. doi: 10.1111/j.1475-097X.2012.01158.x. Epub 2012 Jul 30.
  PMID: 23216760
  responsible party type: Sponsor-Investigator
  investigator affiliation: Loughborough University
  investigator full name: Mrs Hanoof Aljohani
  investigator title: Lead Investigator
  mesh term: Lung Diseases
  mesh term: Lung Diseases, Obstructive
  mesh term: Pulmonary Disease, Chronic Obstructive
  mesh term: Body Weight
  sharing ipd: Yes
  ipd description: All individual patient data (IPD) that underlie results in a publication
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd info type: Analytic Code
  ipd time frame: Data requests can be submitted starting 6 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
  ipd access criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of research chief investigator and/or principal investigator.