The ADAPTation to Therapeutic Resistance Training (ADAPT) Study

Study Overview
=================
Brief Summary
-----------------
In 2018, the Academic Department of Military Rehabilitation (ADMR) published a pilot randomised controlled trial (RCT), demonstrating the feasibility and acceptability of integrating twice-daily blood flow restriction (BFR) training into a busy residential care setting. Following its publication was a guidance note written by the Directorate of Defence Rehabilitation restricting the implementation of BFR training until more evidence can be provided to support its efficacy. This research trial is a fully-powered, multi-centre RCT investigating the efficacy and biological mechanism underpinning BFR therapy in UK military personnel with lower-limb musculoskeletal injury (specifically, persistent anterior knee pain) during residential rehabilitation. This study will aim to optimise both the rehabilitation outcome and improve the time-and cost-effectiveness of the service delivered across UK Defence Rehabilitation and beyond. Results will provide insight and knowledge to the clinical and scientific community to not only those embedded within Defence Rehabilitation, but also those working in civilian sector organisations and professional sport in the UK and abroad.

Official Title
-----------------
Low-load Blood Flow Restriction Exercise Versus Conventional Heavier Load Resistance Training Exercise in UK Military Personnel With Persistent Knee Pain: A Multi-centre Randomized Controlled Trial

Conditions
-----------------
Musculoskeletal Injury, Muscle Weakness

Intervention / Treatment
-----------------
* Other: Resistance Training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: mechanical knee pain for at least three months present with clinical signs and symptoms of knee pain arising from the tibiofemoral or patellofemoral joint diagnosed by sport and exercise medicine physician and/or physiotherapist have reduced occupational employability medical grade secondary to their knee pain report progression of resistance training load within the patient's rehabilitation programme is limited by knee pain aged between 18 and 55 years available to attend for the entire duration of the RRU course and a review appointment 3-months following course. Exclusion Criteria: diagnosed tibial, femoral or patella fracture and/or dislocation; present with instability in the knee resulting from ligament deficiency present with clinical signs and symptoms of patellar tendinopathy have planned surgery over the study period restricted knee range of movement; clinical signs and symptoms of non-musculoskeletal or serious pathological condition (i.e. Inflammatory arthropathy, infection or tumour) or referred pain from non-local pain source present with any physical impairment or co-morbidities (including cardio-vascular disease) precluding the safe participation in the rehabilitation programme and/or assessment procedures Cortico-steroid or analgesic injection intervention within the previous 7-days or previous knee surgery within the last 12 months to the affected limb Medical Exclusion Criteria: History of cardiovascular disease including hypertension, peripheral vascular disease, thrombosis/embolism, ischaemic heart disease, myocardial infarction. History of the following musculoskeletal disorders: rheumatoid arthritis, avascular necrosis or osteonecrosis, severe osteoarthritis. History of the following neurological disorders: Peripheral neuropathy, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, severe traumatic brain injury. Varicose veins in the lower limb Acute viral or bacterial upper or lower respiratory infection at screening Known or suspected lower limb chronic exertional compartment syndrome (CECS) Postsurgical swelling Surgical insertion of metal components at the position of cuff inflation History of any of the following conditions or disorders not previously listed: diabetes, active cancer History of elevated risk of unexplained fainting or dizzy spells during physical activity/exercise that causes loss of balance History of haemorrhagic stroke or exercise induced rhabdomyolysis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-load blood flow restriction training (LL-BFR)<br>Twice daily LL-BFR for 3 weeks | Other: Resistance Training<br>* Comparing two different exercise-based treatment methodologies on the clinical outcomes of individuals with persistent knee pain.<br>|
| Active Comparator: Heavier load resistance training (HL-RT)<br>Three sessions per week for 3 weeks | Other: Resistance Training<br>* Comparing two different exercise-based treatment methodologies on the clinical outcomes of individuals with persistent knee pain.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lower Extremity Functional Scale (LEFS) over time | LEFS is a 20-question patient-reported outcome measure (PROM) that measures functional status in patients with lower limb musculoskeletal injury. Questions on activity vary in physical demand from walking to running on uneven ground. The LEFS is a validated tool and has demonstrated good test-retest reliability and responsiveness in individuals with persistent knee pain. | Baseline, week 3 and week 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) over time |  | Baseline, week 3 and week 15 | 
| Change in Patient Specific Functional Scale over time |  | Baseline, week 3 and week 15 | 
| Change in Musculoskeletal Health Questionnaire (MSK-HQ) over time |  | Baseline, week 3 and week 15 | 
| Change in Tampa Scale of Kinesiophobia (TSK) over time |  | Baseline, week 3 and week 15 | 
| Health Anxiety Depression Scale (HADS) |  | Baseline | 
| Change in International Physical Activity Questionnaire (IPAQ) over time |  | Baseline, week 3 and week 15 | 
| Change in Numeric Pain Rating Scale (NPRS) over time |  | Baseline, week 3 and week 15 | 
| Change in Sport Injury Rehabilitation Beliefs Survey (SIRBS) over time |  | Baseline, week 3 and week 15 | 
| Change in functional Activity Assessment (FAA) over time |  | Baseline and week 15 | 
| Change in five Repetition Maximum Leg Press over time |  | Baseline, week 3 and week 15 | 
| Change in isometric muscle strength of hip and knee using hand-held dynamometer over time |  | Baseline, week 3 and week 15 | 
| Change in single leg heel raises to fatigue over time |  | Baseline, week 3 and week 15 | 
| Change in qualitative assessment of single leg squat (QASLS) over time |  | Baseline, week 3 and week 15 | 
| Change in decline knee bend over time |  | Baseline, week 3 and week 15 | 
| Change in isometric midthigh pull over time |  | Baseline, week 3 and week 15 | 
| Change in counter-movement jump over time |  | Baseline, week 3 and week 15 | 
| Change in knee extension and flexion - maximal isometric voluntary contraction over time |  | Baseline, week 3 and week 15 | 
| Change in muscle volume and anatomical cross sectional area (CSA) using magnetic resonance imaging (MRI) over time |  | Baseline, week 3 and week 15 | 
| Change in pennation angle over time using ultrasonography | Pennation angle measured in degrees | Baseline, week 3 and week 15 | 
| Change in fascicle length over time using ultrasonography | fascicle length measured in mm | Baseline, week 3 and week 15 | 
| Change in single leg squat over time - kinetic and kinematic analysis | 3D motion capture and force plate data will be used to collect kinetic and kinematic data which will be later analysed using inverse dynamics. Force measured in Newtons, Moments measured in Newton/Metres/kg | Baseline, week 3 and week 15 | 
| Change in bilateral squat over time - kinetic and kinematic analysis | 3D motion capture and force plate data will be used to collect kinetic and kinematic data which will be later analysed using inverse dynamics. Force measured in Newtons, Moments measured in Newton/Metres/kg | Baseline, week 3 and week 15 | 
| Change in markers of muscle damage over time | Using fasted blood samples. E.g., Creatine Kinase (units/L) | Baseline, week 3 and week 15 | 
| Change in markers of oxidative stress over time | Using fasted blood samples. E.g., Protein carbonyl (units/L) | Baseline, week 3 and week 15 | 
| Change in markers of inflammation over time | Using fasted blood samples. E.g., Interleukin-6 (pg/ml) | Baseline, week 3 and week 15 | 
| Change in markers of endothelial function over time | Using fasted blood samples. E.g., Vascular endothelial growth factor (µg/L) | Baseline, week 3 and week 15 | 
| Change in daily monitoring of wellness score over time | Subjective patient reported outcome measure of 'wellness' scored using a 5-point likert scale. | Daily for the 3 weeks of rehabilitation | 
| Change in daily monitoring of session rate of perceived exertion (sRPE) over time | Subjective patient reported outcome measure of exertion, scored 0 to 10 (0 = no exertion, 10= maximal exertion) | Daily for the 3 weeks of rehabilitation | 
| Change in daily monitoring of pain over time | Subjective patient reported outcome measure of pain measured using a 0 to 100mm visual analog scale (VAS). 0= no pain, 100 = worst pain | Daily for the 3 weeks of rehabilitation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Musculoskeletal rehabilitation, Blood flow restriction, Resistance training, knee pain, military