Is Low-load Resistance Training With Blood Flow Restriction More Effective Than Traditional Rehabilitation of Military Personnel With Lower Limb Injuries (LIMITLESS)

The Effects of Different Blood Flow Restriction Training Methodologies During the Rehabilitation of Military Personnel With Lower Limb Musculoskeletal Injuries Primarily Limited by Pain: a 2 Part Randomised Controlled Trial (Phase Two)

Pain can be one of the primary limiting factors to progress following musculoskeletal injury and may be caused by trauma or degenerative changes. There are few exercise rehabilitation interventions able to relieve pain, thereby reducing the number of military personnel fit for operations. Low load blood flow restriction (BFR) exercise has been shown to elicit an analgesic response and promote beneficial physiological changes in a variety of clinical populations.

This two phase study, aims to:

• Determine the most effective and feasible BFR resistance exercise protocol for reducing pain in UK military patients.
• Determine the efficacy of an optimal BFR exercise protocol for reducing pain and improving rehabilitation outcomes in UK military patients.
• Identify key physiological mechanisms underpinning any beneficial effect of BFR exercise on pain.

Consequently, results from this study will have direct clinical application and will aid best practice guidelines for the management of pain across Defence Rehabilitation by influencing the future rehabilitation paradigm. The investigators believe the results and impact will be far reaching, providing invaluable insight and knowledge to the clinical and scientific community to not only those embedded within Defence Rehabilitaion, but also those working in civilian sector organisations and professional sport also.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain; Musculoskeletal Pain; Persistent Pain
• Intervention / Treatment: Device: BFR; Other: control group

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Ladlow, PhD; Phone Number: 3407 +44 1509 251 500; Email: peter.ladlow100@mod.gov.uk
• Study Contact Backup: Name: Luke Hughes, PhD; Email: luke4.hughes@northumbria.ac.uk

Study Locations

• United Kingdom
  • Loughborough, United Kingdom, LE12 5QW
    • Defence Medical Rehabilitation Centre, Stanford Hall
    • Contact: Peter Ladlow, PhD; Phone Number: 3407 +44 1509 251 500; Email: peter.ladlow100@mod.gov.uk
    • Contact: Luke Gray

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Serving UK military personnel,
• Aged 18-55,
• Has unilateral lower limb injury whereby pain is the primary limiting factor hindering progression, as diagnosed by relevant consultant and team,
• Reduced occupational employability and function,
• Scheduled to attend DMRC Stanford Hall for 3 week residential rehabilitation course.

MSK-Specific Exclusion Criteria

• Any medical contraindication related to BFR*
• Non-musculoskeletal or serious pathological condition (i.e. Inflammatory arthropathy, infection or tumour)
• Spinal or referred pain from non-local pain source
• Any pre-diagnosed physical impairment or co-morbidities (including cardio-vascular disease) precluding the safe participation in the rehabilitation programme and/or assessment procedures
• Corticosteroid or analgesic injection intervention to the affected area within the previous 7 days

• Currently pregnant, or have not yet completed a return to work assessment following the birth of your child.

  *Medical-Related Exclusion Criteria

• History of cardiovascular disease (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: Alzheimer's disease, amyotrophic lateral sclerosis, peripheral neuropathy, 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) (tourniquet raises intra-compartmental muscle pressure),
• 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 and/or exercise that causes loss of balance,
• Increased risk of haemorrhagic stroke, exercise induced rhabdomyolysis,
• Currently pregnant.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BFR; The intervention involves placing a pneumatic tourniquet system over the proximal thigh. The cuff will be inflated to either 40% or 80% of limb occlusion pressure during lower limb strengthening exercises, as determined by Phase One (2318/MODREC/24a). These exercises include leg press and knee extensor exercises. Four sets (30,15,15,15 repetitions) performed at 20% of one repetition maximum.	Device: BFR; The intervention involves placing a pneumatic tourniquet system over the proximal thigh. The cuff is inflated to either 80% or 40% of limb occlusion pressure during lower limb strengthening exercises, as determined by Phase One (2318/MODREC/24a). These exercises include leg press and knee extensor exercises. Four sets (30,15,15,15 repetitions) performed at 20% of one repetition maximum in Week 1, 25% in Week 2 and 30% in Week 3.; Other Names: blood flow restriction training; occlusion training
Active Comparator: Control; Standard residential rehabilitation consists of; (1) exercise-based therapy delivered in group settings and individually to address a variety of physical components relating to their pathology (e.g., balance and co-ordination, cardiovascular endurance, mobility and flexibility, motor control and dynamic stability, and muscular strength), (2) patient education sessions (e.g., activity modification, behavioural change, and focusing on pain management), and (3) one-on-one support sessions (e.g., dietetics, occupational therapy, physiotherapy, podiatry, prosthesis/orthosis specialists, social workers, and speech and language therapists).	Other: control group; Standard residential rehabilitation consists of; (1) exercise-based therapy delivered in group settings and individually to address a variety of physical components relating to their pathology (e.g., balance and co-ordination, cardiovascular endurance, mobility and flexibility, motor control and dynamic stability, and muscular strength), (2) patient education sessions (e.g., activity modification, behavioural change, and focusing on pain management), and (3) one-on-one support sessions (e.g., dietetics, occupational therapy, physiotherapy, podiatry, prosthesis/orthosis specialists, social workers, and speech and language therapists).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brief Pain Inventory	The BPI is a patient administered, multi-dimensional, pain assessment tool commonly used within musculoskeletal clinical practice. Higher scores on the 9- item short form indicate greater interference with function, or greater pain intensity.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-RM Testing	5-RM assessment on leg press and leg/knee extension machines (leg/knee extension pre-intervention only) to assess the participants strength, and inform % load for intervention period. Testing procedure: 5-minute cycling warm up, followed by 10-rep exercise specific warm up, and then successive attempts at performing a 5RM on injured limb only. The authors acknowledge that due to the likely interference effect of a pain response, performing a 'maximum effort' physical task in a lower limb injured cohort is unlikely to yield a true measure of MSK performance. It is more accurate to describe outcome scores as providing an 'indication' of participant performance and progression. We will highlight this as a potential weakness in our study but feel this is a challenge in the measurement of muscle force / strength in all MSK injury research. All outcomes measured will be implemented and recorded based upon a best effort at the time of assessment.	T0, Pre-Admission (Day 0); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Numerical Pain Rating Scale	To assess the feasibility and tolerability of the BFR-RT interventions, a participant monitoring booklet will be used throughout the intervention period. The Numerical Pain Rating Scale (NPRS) for injury-specific pain and localised muscle soreness will be collected pre-intervention, immediately post-intervention, and 1-hour post-intervention for each BFR-RT session.	T2, Daily (before, immediately-post, and 1 hour-post each BFR session; days 1-5, 6-10 and 11-15).
Sessional Rate of Perceived Exertion	To assess the feasibility and tolerability of the BFR-RT interventions, a participant monitoring booklet will be used throughout the intervention period. Sessional Rate of Perceived Exertion (scored 0-10; 0=no effort, 10=maximal effort) will be collected following each BFR-RT session.	T2, Daily (immediately post-intervention; day 1-5, 6-10 and 11-15).
Training Load	To assess the feasibility and tolerability of the BFR-RT interventions, a participant monitoring booklet will be used throughout the intervention period. To quantify training load, the following calculation will be conducted following each BFR-RT session; sets x reps x load (kg). Specific Example: BFR-RT Leg Press at 25kg 1 set x 30 reps + 3 sets x 15 reps = 75 reps 75 (reps) x 25 (kg) = 1875 (training load)	T2, Daily (immediately post-intervention; day 1-5, 6-10 and 11-15).
Copenhagen Hip and Groin Score	The Copenhagen Hip and Groin Score is a patient administered, multi dimensional, pain assessment tool commonly used to assess symptomatic and functional burden associated with hip and groin pathology. Scored from 0-100, lower scores on the HAGOS represent greater symptomatic and functional burden. The MCID per domain is 8, 8, 9, 10, 11, and 12 points for hip-related QOL, symptoms, pain, sport and recreation activities, ADL, and participation in physical activities, respectively.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Lower Extremity Function Scale	The LEFS is a patient-reported outcome measure that measures functional status in patients with lower limb musculoskeletal injury. Ability to perform 20 activities, ranging from walking to running on uneven ground, are self-reported from 0-4 with higher scores indicating better function.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Daily Morning Wellbeing	To assess the feasibility and tolerability of the BFR-RT interventions, a participant monitoring booklet will be used throughout the intervention period. Daily morning wellbeing questions (fatigue, muscle soreness, sleep quality, stress levels and mood) will be asked each morning using a Likert scale (1-5), before the first BFR-RT session.	T2, Daily (before BFR session; days 1-5, 6-10 and 11-15).
Isometric Mid-Thigh Pull	The isometric mid-thigh pull is a test that can assess multiple derivatives of maximal lower-limb muscle strength including, peak force, rate of force development and limb asymmetry. The participant is asked to stand on force plates (set within a mid-thigh pull rig) and then pull on the mid-thigh bar at maximal force.	T0, Pre-Admission (Day 0); T3, Start and End of Residential Rehabilitation Week (Day 5, 6, 10 and 11); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Pressure Pain Threshold Testing	Pressure pain threshold assessment can help define regions of mechanical hypersensitivity, a common trait of central sensitisation. By utilising a digital pressure algometer (1cm^2 probe, Model FPX 50, Wagner Instruments, USA), the amount of pressure at which the sensation of pressure becomes unpleasant is deemed the PPT, with lower pressure values being indicative of central sensitisation.	T0, Pre-Admission (Day 0); T1, Course Admission (Day 1); T2, Daily (Day 1-5, Day 6-10, Day 11-15); T3, Start and End of Residential Rehabilitation Week (Day 5, 6, 10 and 11); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Foot and Ankle Disability Index	The Foot and Ankle Disability Index is a 26-item ankle and foot specific, patient- reported, questionnaire which considers ADLs, function, pain and sleep. Each item is scored from 0 (unable to do/unbearable pain) to 4 (no difficulty at all/no pain), with a total point value reaching a maximum of 104; however, the PROM is scored as a percentage and a lower percentage indicates greater levels of disability and/or pain. To date, no MCID has been reported for the Foot and Ankle Disability outcome measure.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Knee Injury and Osteoarthritis Outcome Score	The Knee Injury and Osteoarthritis Outcome Score is a five domain, patient- administered questionnaire, used to monitor disease course and outcomes following knee injury/OA or surgery. The five domains, ADL, knee-related QOL, other symptoms, pain, and sport and recreation function, are scored on a 0- 100 scale, with a higher score indicating better function and less symptoms. The MCID for the Knee Injury and Osteoarthritis Outcome Score is 10-points for each domain.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Leeds Assessment of Neuropathic Symptoms and Signs	The Leeds Assessment of Neuropathic Symptoms and Signs is a self-reported questionnaire with a primary aim of distinguishing pain of a neuropathic origin, without the need for clinical assessment. The questionnaire consists of 7 questions, with a higher score suggesting the pain is predominantly of neuropathic origin. To date, no MCID has been reported for the Leeds Assessment of Neuropathic Symptoms and Signs.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Non-Arthritic Hips Score	The Non-Arthritic Hips Score is a 20-item, self-reported, questionnaire covering four domains (activities, function, pain and symptoms), in patients without arthritic pathology. The summative score for Non-Arthritic Hips Score is between 0-100, with 100 representing a perfectly functioning hip. The MCID for this outcome measure is 8-points.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Victorian Institute for Sport Assessment - Achilles	The Victorian Institute for Sport Assessment - Achilles is a patient-reported questionnaire designed to assess the severity of Achilles tendinopathy. With questions focused on the domains of function in ADLs, pain, and sporting activity, the questionnaire is scored out of 100 (100 = asymptomatic); however, a score less than 60 is often seen in Achilles tendinopathy populations. The MCID is set at 14-points for mid-portion Achilles tendinopathy, and 6.5 points for insertional tendinopathy.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Victorian Institute for Sport Assessment - Gluteal	The Victorian Institute for Sport Assessment - Glutealwas designed to evaluate the severity of disability in greater trochanteric pain syndrome populations. Formulated in the same manner as other Victorian Institute of Sport Assessment tendinopathy measures, the Victorian Institute for Sport Assessment - Gluteal is scored out of 100, with a greater score associated with greater function and less symptom impairment. There is currently no MCID reported within the literature for the Victorian Institute for Sport Assessment - Gluteal.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Victorian Institute for Sport Assessment - Hamstring	The Victorian Institute for Sport Assessment - Hamstring was designed in the style of previous Victorian Institute of Sport Assessment tendinopathy outcome measures, but specifically to evaluate the severity of symptoms, function and ability to play sports in those with proximal hamstring tendinopathy. Scored out of 100, with higher scores being associated with greater function and less symptomatic impairments. A 4-point reduction was reported in the literature as being the threshold required to detect for true change when the standard error of measurement is considered; however, an MDIC of 22-points has been reported.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Victorian Institute for Sport Assessment - Patella	The Victorian Institute for Sport Assessment - Patella is an 8 question, patient- reported measure developed specifically to subjectively assess the severity of symptoms, function and ability to play sports in those with patella tendinopathy . Scored out of 100, a greater score is associated with greater function and less symptom impairment, with 0 being the theoretical minimum score. The MCID for the Victorian Institute for Sport Assessment - Patella is 13-points.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
McGill Pain Questionnaire - Short Form	The McGill Pain Questionnaire short form asks patients to rate 15 descriptors of affective and sensory feelings of pain (i.e., aching, sickening, throbbing) on a 1 (none) to 4 (severe) scale and completed a NPRS for average pain intensity. The affective and sensory section of the McGill Pain Questionnaire short form is graded from 15 to 45, with a higher score indicating a greater level of pain intensity and sensory variation; meanwhile, the NPRS of average pain is considered a separate entity. The MCID for this outcome measure is 5-points.	T0, Pre-Admission (Day 0); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Pain Catastrophizing Scale	The Pain Catastrophizing Scale is a 13-item instrument that assesses helplessness, magnification and rumination to encompass the catastrophizing of musculoskeletal persistent pain. With each item scored 0 (not at all) to 4 (all the time), a higher score indicates greater catastrophizing of pain. A MCID of 8- and 11-points for no/low catastrophizers and catastrophizers (total score = >30 points), respectively, has been reported within the literature.	T0, Pre-Admission (Day 0); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Tampa Scale of Kinesiophobia	The Tampa Scale of Kinesiophobia is a 17-item questionnaire used to evaluate kinesiophobia in people with persistent musculoskeletal pain, by assessing activity avoidance (i.e., reflects beliefs of an activity that may result in an increase of pain, or cause injury) and somatic focus (i.e., reflects beliefs and underlying of serious conditions). With each item scored 1 (strongly disagree) to 4 (strongly agree), a higher score denotes greater levels of fear of movement and/or re-injury. The MCID for Tampa Scale of Kinesiophobia is a 4-point reduction.	T0, Pre-Admission (Day 0); T3, End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Fatigue Assessment Scale	The Fatigue Assessment Scale is a 10-question, self-reported questionnaire that covers mental and physical fatigue. The cumulative score for the Fatigue Assessment Scale ranges from 10 to 50, with each question is scored from 1 (never) to 5 (always), with two requiring reverse scoring. A higher score indicates greater levels of fatigue, with scores >22 representing fatigue levels are greater than "healthy" or "normal" levels. The MCID for the Fatigue Assessment Scale is 4-points.	T0, Pre-Admission (Day 0); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Temporal Summation	Temporal summation is form of quantitative sensory testing that utilised mechanical pressure to gain insight to which pain mechanisms are involved for an individual patient. Temporal summation assessment resembles the "wind-up" effect, or second pain stimulus, often seen in persistent pain populations. To assess temporal summation, at a pre-determined location closest to the individuals injured site, ten consecutive ramping pulses building to the mean pressure of the respective PPT score will be applied over 5s with a 1s hold, before immediate release, with 1s rest interval before the next pulse. At the peak of each pulse, the participant will be asked to rate their pain on the NPRS scale. The first NPRS value will act as an anchor/baseline. Each NPRS will be normalised via subtraction of the initial NPRS value. To reflect changes in temporal summation across the series, the NPRS epochs (mean NPRS rating of peaks; I 2-4, II 5-7, and III 8-10) will be calculated for analysis.	T0, Pre-Admission (Day 0); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Beta Endorphin	Beta-endorphin is a neuropeptide produced in the central nervous system and pituitary gland in response to pain or exercise will be collected via venepuncture or cannulation to assess the acute response of BFR-RT on hypoalgesia.	T0, Pre-Admission (Day 0); T2, Daily (Day 2, 7 and 11 pre-, post- and 1-hour post-intervention, Day 3, 8, and 12 pre-intervention); T3, Start and End of Residential Rehabilitation Week (Day 5 and 10); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Interluekin-6	Inflammatory cytokine, interleukin-6, is thought to be a driver for the development of pathological pain and has been shown to have elevated levels in persistent pain populations. This will be collected via venepuncture or cannulation to assess the response of BFR-RT on systemic inflammatory markers.	T0, Pre-Admission (Day 0); T3, Start and End of Residential Rehabilitation Week (Day 5, 6, 10 and 11); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Tumour Necrosis Factor Alpha	Inflammatory cytokine, tumour necrosis factor alpha, is thought to be a driver for the development of pathological pain and has been shown to have elevated levels in persistent pain populations. This will be collected via venepuncture or cannulation to assess the response of BFR-RT on systemic inflammatory markers.	T0, Pre-Admission (Day 0); T3, Start and End of Residential Rehabilitation Week (Day 5, 6, 10 and 11); T4, Post-Intervention/Pre-Course Discharge (Day 15)
Medication Record Sheet	The medication record sheet is utilised to show what current medications each participant is using for their pathology. The drug name, drug purpose, dose size and frequency is noted. This outcome measure is taken at baseline only (T0).	T0, Pre-Admission (Day 0).
Demographics Questionnaire	Personal and demographic characteristics including age, body height, body mass, body mass index, duration of symptoms, previous injuries, previous treatment, military occupation, duration of military service, smoking and drinking habits. This outcome measure is taken at baseline only (T0).	T0, Pre-Admission (Day 0).
Health Anxiety Depression Scale	The Hospital Anxiety and Depression Scale (HADS) is a 14-item self-reported measure designed to assess anxiety and depression symptoms in medical patients, with emphasis on reducing the impact of physical illness on the total score. This outcome measure is taken at baseline only (T0).	T0, Pre-Admission (Day 0).
Musculoskeletal Health Questionnaire	The MSK-HQ is a self-reported questionnaire that allows people with musculoskeletal conditions to report their symptoms and quality of life in a standardised way. This outcome measure is taken at baseline only (T0).	T0, Pre-Admission (Day 0).

Collaborators and Investigators

• Sponsor: Defence Medical Rehabilitation Centre, UK
• Collaborators: Northumbria University
• Investigators: Principal Investigator: Peter Ladlow, PhD, Defence Medical Rehabilitation Centre, UK

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2025
• Primary Completion (Estimated): May 29, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: September 28, 2024
• First Submitted That Met QC Criteria: September 30, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: pain; blood flow restriction; musculoskeletal
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Pain
• Other Study ID Numbers: 2318/MODREC/24b

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon reasonable request, grouped data (i.e., data that cannot individually identify participants) may be shared to other research groups for the advancement of research and clinical practices, by the chief investigator.
• IPD Sharing Time Frame: Upon completion of the dissemination of research findings (i.e., publications and conference proceedings).
• IPD Sharing Access Criteria: Most data will be openly available, but due to privacy concerns, some data regarding participants are available only to bona fide researchers working on a related project, subject to the completion of a non-disclosure agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No