The Feasibility and Effects of Low-load Blood-flow Restricted Exercise Following Spinal Cord Injury

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Brief Title

The Feasibility and Effects of Low-load Blood-flow Restricted Exercise Following Spinal Cord Injury

Official Title

The Feasibility and Effects of Low-load Blood-flow Restricted Exercise Following Spinal Cord Injury

Brief Summary

      Spinal cord injury (SCI): The World Health Organization estimates an incidence of 250,000 to
      500,000 per year worldwide. In Denmark 130 new cases of SCI per year. SCI is a devastating
      condition: paresis/paralysis of the skeletal muscles below the injury site, partial or
      complete inability to walk, move and/or feel. Other sequelae are: infections, lifestyle
      diseases (cardiovascular, diabetes, nephrologic disease), mental wellbeing/suicide-risk
      profoundly raised , quality of life, next-of-kin affection. Recovery of motor function is
      high clinical priority and crucial for improved ADL outcomes. Strength training regimens have
      shown improved muscle strength in healthy subjects using near-maximal voluntary effort
      contractions, and few studies have demonstrated similar effects in a SCI population. Atrophy
      and fatigability and spasticity may reduce practical implementation for rehabilitation.
      Therefore, low-load blood-flow restricted exercise (BFRE) may prove beneficial as supplement
      to traditional rehabilitation, increasing muscle strength and inducing hypertrophy in healthy
      persons. BFRE is performed as low-intensity strength training (20-30 % of max) while
      simultaneously involving the use of circumferential placement of cuffs during exercise, to
      maintain arterial inflow to the muscle while preventing venous return. Based on existing
      scientific evidence, BFRE is acknowledged as a safe regime without serious side effects.
      Previously, the method has shown increased muscle strength and inducing skeletal muscle
      hypertrophy in addition to improvement in gait performance in individuals with various
      diseases causing reduced mobility. Purposes of this PhD project: to investigate the
      feasibility and effects of BFRE in individuals living with the consequences of SCI.
    

Detailed Description

      BACKGROUND Spinal cord injury (SCI) represents a major health concern; the World Health
      Organization estimates an incidence of 250,000 to 500,000 per year worldwide. On average in
      Denmark we register 130 new cases of SCI per year. SCI is a devastating condition, in which
      paresis/paralysis of the skeletal muscles below the injury site results in a partial or
      complete inability to walk, move and/or feel. Concurrent to functional disabilities,
      infections, lifestyle diseases such as cardiovascular diseases are frequent sequelae due to
      inactivity and overweight. Affecting primarily younger and previously healthy individuals
      traumatic SCI also profoundly impacts the mental wellbeing of the patients and also their
      next-of-kin; quality of life (QoL) suffers and subsequently the risk of suicide for patients
      with SCI increases by two to five times as compared to the background population.

      While a substantial effort is being put into the rehabilitation of individuals with SCI,
      large gaps in knowledge still exist on this area. Recovery of motor function is of high
      clinical priority as it is fundamental for improved ADL outcomes.

      While various strength training regimens have been shown to increase muscle strength in
      neurologically intact individuals using near-maximal voluntary effort contractions, few
      studies have demonstrated similar effects from strength training regimens in persons with
      SCI. Complications such as atrophy and easily fatigable neuromuscular system with various
      degrees of spasticity often make these kinds of regimes less practical and rewarding for
      rehabilitation. Therefore, the addition of low-load blood-flow restricted exercise (BFRE) may
      prove beneficial as a supplement to traditional rehabilitation. Notable, BFRE is found to
      increase muscle strength and induces skeletal muscle hypertrophy in healthy individuals.
      Typically, BFRE is performed as low-load strength training (20-30 % 1 Repetition Maximum
      (RM)) combined with concurrent partial occlusion of limb blood flow by means of pneumatic
      cuffs placed proximal at the limb, to restrit arterial inflow to the exercising muscle and
      preventing venous return. Based on existing scientific evidence and applying
      pre-exercisescreening for known risk factors such as vascular dysfunction (AD) or prior
      history of trombosis, BFRE is acknowledged as a safe exercise regime without serious side
      effects. Previously, the method has shown increased muscle strength and skeletal muscle
      hypertrophy in addition to improvements in gait and sit-to-stand performance in individuals
      with various diseases causing reduced mobility.

      The aim of this PhD project is to;

        1. To conduct a pilot study for investigate the safety and feasibility of low-load BFRE
           training in adults with SCI

        2. To conduct a RCT to investigate the effects of low-load blood-flow restricted exercise
           (BFRE) on physical function and neuromuscular recovery in individuals with SCI

      The hypotheses are as following;

        -  The BFRE training protocol will be safe and applicable to individuals with a spinal cord
           injury below Th7

        -  Participants randomized to active BFRE treatment will exhibit greater increases in
           physical function and lower extremity muscle strength and muscle volume, respectively,
           than partici-pants receiving sham BFRE. Treatment effects will be documented using
           functional disability assessment tools combined with measurements of maximum voluntary
           isometric muscle strength, rapid force capacity (rate of force development: RFD) and
           cross sectional area of the trained muscles.

        -  Participants allocated to active BFRE will exhibit less neuropathic pain and reduced use
           of analgesic medication than participants receiving sham BFRE. This will be documented
           by standardized questionnaires and quantitative assessment methods.

      Feasibility Study (Study I)

      The feasibility study will be conducted by the applicant, Anette Bach Jønsson (ABJ).
      Consecutively, prior to the RCT, 3 individuals with a SCI will be recruited between 1/4 2020
      - 31/7 2021 using the same recruitment strategy and in- and exclusions criteria as in the
      RCT. Additionally, 3 in-patients with sub-acute SCI (Time since injury > 1 month and > 1
      year) will be recruited. The 6 patients will follow the same initial examination and training
      protocol as in the active BFRE group as described below. However, the training will be
      performed twice a week for 2 weeks.

      Outcome variables:

      The following outcome measurements will be performed at pre- and postintervention.

      Muscle testing Maximum, voluntary, isometric muscle strength that participants are able to
      exert on a portable knee dynamometer (S2P, Science to Practice, Ljubljana, Slovenia).
      Portable dynamometers are considered as valid and reliable instruments for measuring
      strength. Measurements of muscle torque (Nm) and Rate of Force Development (RFD, Nm/s) will
      be obtained.

      Blood samples Blood samples will be obtained pre (30 minutes) and post (0-60 minutes) the
      first and last training session (4 blood samples in total). In-house physicians or laboratory
      technician will be responsible for retrieving the blood samples. Markers of coagulation
      (fibrinogen and D-dimer), fibrinolysis [tissue plasminogen activator (tPA)] and inflammation
      [high sensitivity C-reactive protein (hsCRP)] will be analyzed. The blood samples will be
      destroyed immediately after analyzing. The results will be obtained through the electronic
      patient record.

      Feasibility Tolerance to the selected occlusion pressure and pain perception throughout
      training will be obtained by using the Numeric Rating Scale (NRS 0-11 point) and interview.
      Adherence to the planned training scheme will as well be recorded.

      Safety considerations Autonomic dysreflexia (AD) may be a potentially life-threatening
      condition for people with a high injury level (Th6 and above, Tetraplegia) and may be
      provoked by cutaneous stimulation such as pain. Therefore, patients at risk of AD will be
      excluded and the ISCOS Autonomic Standards Assesment Form will be fulfilled before and after
      completion.

      Eligibility for inclusion will be approved by specialist neurologist. Training sessions are
      coordinated with the physician-on-call. To ensure patient safety blood pressure and heart
      rate will be measured throughout training and will be closely monitored. In case of serious
      adverse events the MD on duty will be contacted immediately. During study I and II regular
      safety meetings in the research group will be scheduled. If serious adverse events occurs in
      study I, a reconsideration of the design of study II would be necessary (e.g. changes in
      BFR-dosage) and further pilot testing would be necessary.

      Randomized controlled trial (Study II)

      Methods Initial examination After inclusion, medical history, demographic and anthropometric
      data, spasticity level and the neurological level of SCI will be obtained. Spasticity level
      will be measures using Modified Ashworth Scale (MAS). Neurological level using the
      International Standards for Neurological Classification of SCI (ISNCSCI). Information about
      trauma date and reason, plan of standard care during hospitalization (physiotherapy,
      occupational therapy, hydrotherapy and other physical treatments/activities) will be obtained
      through the electronic patient record. Furthermore, functional disability assessment in
      addition to para-clinical tests will be conducted

      Intervention/Control Prior to the first training session, participants will be randomized to
      either active BFRE (n=14) or sham BFRE (n=14), while controlling for age and gender. BFR will
      be performed in the aBFRE group by use of pneumatic occlusion cuffs placed proximally on the
      thigh close to the inguinal fold, using an occlusion pressure corresponding to 40 % of seated
      arterial occlusion pressure (AOP). The individual AOP will be documented at baseline using
      doppler ultrasound (Siemens ACUSON S2000TM). Previous studies have shown that this pressure
      level can promote significant muscle adaptations to a similar degree and are associated with
      significantly less discomfort than higher occlusion pressures. The occlusion pressure of the
      participants in sham BFRE group will be 10mmHg.

      Subjects from both groups will participate in 45 minutes of low-intensity BFRE (30-40% 1RM)
      of the lower extremities twice/week for 8 weeks, consisting of 5 minutes light warm-up of
      low-intensity cycling followed by 4 sets (30x15x15x15 repetitions, 45 sec pause between sets)
      of seated leg extension and leg curl with BFR. A 3 minutes pause is allowed between exercises
      where the cuff will be deflated. Blood pressure will be measured with a temporal resolution
      of approx. 5 minutes throughout training.

      Data analysis Within-group changes from baseline to follow-up will be analyzed using paired
      parametric or nonpar-ametric methods. Between-group differences will be compared as unpaired
      data using a parametric or nonparametric methods. The type 1 level of significance is set at
      0.05. The results will be analyzed according to the intention-to-treat principle. According
      to sample-size calculation with an 80 % power and 5 % level of significance a difference of
      20 % on MVC between the active and sham BFR groups are possible to detect with 24
      participants. A total of 28 participants will be recruited to take a 20 % dropout rate into
      account. A difference of 20 % on MVC is expected as a realistic suggestion as a minimal
      clinical important difference.

      Practical framework This PhD project has received permission from SCIWDK. The initial
      examination and tests at baseline and follow-up will be conducted at SCIWDK's laboratory by
      the applicant, Anette Bach Jønsson (ABJ). She is an experienced physiotherapist. Training
      sessions will be guided and supervised by in-house physiotherapists and ABJ.

      Ethical considerations:

      The study has been approved by The Danish Scientific Ethics Commission (Ref No.
      1-10-72-290-18), and by Data Protection Agency (Datatilsynet, Ref No. 1-16-02-640-18) and has
      been reported to Clinicaltrials.gov.

      Economy: Not described here
    


Study Type

Interventional


Primary Outcome

Changes in MVC

Secondary Outcome

 Change in Rate of force development (RFD)

Condition

Spinal Cord Injuries

Intervention

BFRE

Study Arms / Comparison Groups

 active BFRE
Description:  14 consecutive paraplegic SCI patients are block-randomized to active arm

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

28

Start Date

May 1, 2020

Completion Date

October 31, 2024

Primary Completion Date

February 28, 2024

Eligibility Criteria

        Inclusion Criteria:

          -  SCI level lower than Th7

          -  Duration of SCI > 1 year,

          -  18 years of age or older

          -  Exhibit a grade 2, 3 or 4 muscle function of the knee flexors and/or extensors

          -  Classification of grades A, B, C or D on the International Standards for Neurological
             Classification of Spinal Cord Injury (ISNCSCI) scale

          -  Cognitive ability to follow instructions

        Exclusion Criteria:

          -  Substance abuse

          -  Severe mental illness

          -  Uncontrolled hypertension

          -  Severe arteriosclerosis, coronary arterial disease

          -  Autonomic dysreflexia

          -  Deep venous thrombosis (or severe coagulation dysfunction)

          -  Collagen diseases such as Ehlers-Danlos Syndrome and Marfan's Syndrome

          -  Severe neuropathies
      

Gender

All

Ages

18 Years - 100 Years

Accepts Healthy Volunteers

No

Contacts

Helge Kasch, MD, PhD, 78446152, [email protected]

Location Countries

Denmark

Location Countries

Denmark

Administrative Informations


NCT ID

NCT03690700

Organization ID

BFRE_LE


Responsible Party

Principal Investigator

Study Sponsor

Spinal Cord Injury Centre of Western Denmark

Collaborators

 University of Southern Denmark

Study Sponsor

Helge Kasch, MD, PhD, Principal Investigator, Spinal Cord Injury Centre of Western Denmark


Verification Date

June 2021