Clinical trial NCT04448236: Effect of Blood Flow Restriction Resistance Exercises in COPDAE In-patient Rehabilitation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Acute Exacerbation of COPD
Keywords: muscle strength
COPDAE
BFRRE
isometric knee extension
Lead sponsor: Hospital Authority, Hong Kong
Sponsor class: OTHER_GOV
First posted: 2020-06-25
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. COPD acute exacerbation (COPDAE) as the primary diagnosis for hospitalization or transfer to pulmonary wards of the Haven of Hope Hospital
2. Able to walk under supervision
3. Understand instruction in Cantonese and can give informed consent.

Exclusion Criteria:

1. Concomitant acute cardiac event
2. Severe hypertension (BP \> 180/100)
3. History of venous thromboembolism
4. History of peripheral vascular disease
5. Absence of posterior tibial or dorsalis pedal pulse
6. History of revascularization of the extremity
7. History of lymphectomies
8. Extremities with dialysis access
9. Vascular grafting
10. Current extremity infection
11. Active malignancy
12. Open fracture / soft tissue injuries
13. Amputation to the lower extremity
14. Expected hospitalization less than 2 weeks on admission
15. Medications known to increase clotting risks

Primary outcomes:
measure: Change of Maximal Voluntary Isometric Contraction (MVIC) of Knee Extension of the Dominant Leg in 3 Weeks
timeFrame: baseline and 3 weeks (after 10-12 sessions of training)
Secondary outcomes:
measure: Change of Scores of Short Physical Performance Battery (SPPB) in 3 Weeks
timeFrame: baseline and 3 weeks (after 10-12 sessions of training)
measure: Change of Hand Grip Strength in 3 Weeks
timeFrame: baseline and 3 weeks (after 10-12 sessions of training)
measure: Change of Health Related Quality of Life in 3 Weeks
timeFrame: baseline and 3 weeks (after 10-12 sessions of training)
measure: Average Pain Score of Each Training
timeFrame: pain score before, immediate and 5-minute post exercise;
measure: Reasons of Drop-out of Blood Flow Restriction Resistance Exercise
timeFrame: baseline to 3 weeks (after 10-12 sessions of training)
measure: Feasibility of BFR Exercise
timeFrame: baseline and 3 weeks (after 10-12 sessions of training)
measure: Unplanned Readmission Rate on 1 Month Post Discharge
timeFrame: 1 month after the discharge of patients in the study
measure: 6-minute Walk Test Distance Gain
timeFrame: baseline and 3 weeks (after 10-12 sessions of training)
measure: Acceptability of Blood Flow Restriction Resistance Exercise
timeFrame: Acceptance scale will be assessed immediately after the program after 3 (after 10-12 sessions of training)
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Haven of Hope Hospital
Study officials:
affiliation: Hospital Authority, Hong Kong
name: chung wai LAU, MBBS
role: PRINCIPAL_INVESTIGATOR
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