Enhancing Medial Knee Pain Rehabilitation : A Clinical Trial On The Effectiveness Of Blood Flow Restriction In Combination With Targeted Exercises For Adult With Varus Deformity

NCT ID: NCT07283237

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-08
• Study Completion Date: 2026-10-31

Brief Summary

Background:

Medial knee pain is common in active adults with varus deformity and limits daily and sports activities. Standard physiotherapy improves symptoms but often fails to achieve optimal muscle adaptation due to pain-limited loading. High Tibial Osteotomy (HTO) is indicated when the hip-knee-ankle (HKA) angle <177° (≥3° varus), particularly with symptomatic medial OA and preserved lateral compartment. Mild, moderate, and severe varus alignments correspond to 3°-5°, 6°-8°, and ≥9°, respectively. Blood Flow Restriction (BFR) training enables strength and hypertrophy gains at low intensities by partially restricting venous flow, reducing joint stress while promoting muscle activation. Evidence supports BFR use in knee OA for improving pain, strength, and quality of life, but its effect in varus-related medial knee pain remains unclear. This trial examines whether combining BFR with targeted strengthening offers superior outcomes to conventional exercise.

Aim:

To investigate the effectiveness of BFR combined with targeted exercises in adults with varus deformity and medial knee pain.

Methods:

A randomized controlled trial will be conducted in an outpatient setting. Eighty active adults (30-55 yrs, BMI 18-25) with medial knee pain and mild-moderate varus deformity (2° < HKA ≤ 10°) will be enrolled. Inclusion requires Kellgren-Lawrence grade 1-3 OA; exclusions include BMI > 25, prior knee surgery, DVT, vascular disease, pregnancy, or neurological/musculoskeletal disorders affecting lower limbs. Sample size (n = 30; adjusted to 80 for attrition) was calculated via G*Power (f = 0.35, α = 0.05, power = 0.80). Participants will be randomized into:

• Control group: Specific exercise program for hip adductors, abductors, internal rotators, and knee extensors.
• BFR group: Same protocol performed with BFR using Smart Tools Plus (LLC, USA) cuff at 40-80% limb occlusion pressure (LOP). Cuffs remain inflated during sets and deflated between them (1-min rest). Adverse events (pain, numbness, discoloration) will be monitored.

Assessment timeline: baseline, 6 weeks, 3 months, and 6 months. Outcomes include:

• Primary: Oxford Knee Score (OKS).
• Secondary: LEFS, NPRS, SF-36, MMT (hip flexors, adductors, internal rotators), radiographic measures (HKA, MLDFA, MPTA), and recurrence rate within 1 year.

Muscle strength will be measured using a VALD handheld dynamometer. Radiographs will be interpreted by a blinded radiologist; functional and pain scales by a blinded assessor.

Randomization and blinding:

Participants will be alternately allocated (1:1). The assessor will remain blinded to group assignment (single-blind design).

Statistical analysis:

Quantitative variables will be expressed as mean ± SD and qualitative data as frequencies. Repeated-measures ANOVA and appropriate comparative tests will assess between- and within-group differences. Significance set at p < 0.05.

Expected outcome:

It is hypothesized that combining BFR with targeted exercises will yield greater improvements in pain, function, and muscle strength than conventional exercise alone, offering a promising conservative option for active adults with varus-related medial knee pain.

Detailed Description

Background:

Medial knee pain, frequently observed in active adults with varus deformity, is a common musculoskeletal issue that impairs daily function and participation in sports (1). Standard conservative treatments, such as physiotherapy and strengthening exercises, can reduce pain and improve function, but often fail to achieve optimal muscle adaptation due to pain-limited force production (6). Common Surgical Thresholds for Varus Alignment: High Tibial Osteotomy (HTO) - most common for medial compartment OA with varus: HKA < 177° (i.e., >3° varus), Clinical indication often begins at 5°-6° of varus (HKA ~175° or less) with pain and medial OA, Absolute indications: Symptomatic medial knee OA, HKA angle ≤ 174° (≥6° varus), Age <60 (ideally), active patients and Preserved lateral compartment (1). Another reference states that a moderately active individual with joint stability, between 40-65 years of age, with isolated joint line pain, body mass index <30, mal-alignment <15°, metaphyseal varus, good range of motion, high-demand patient, non-smoker, and with some degree of pain endurance capacity are the indications for HTO (2). According to (3) an Isolated high tibial osteotomy was done based on mFTA, varus alignment was categorized as "mild" (3°-5°), "moderate" (6°-8°), or "severe" (≥ 9°) Blood Flow Restriction (BFR) training has emerged as an innovative adjunct, enabling significant gains in muscle strength and hypertrophy at lower exercise loads by partially restricting venous blood flow during exercise (4). This technique is particularly beneficial for individuals who cannot tolerate high-resistance training, as it minimizes joint stress while promoting muscle growth and improved function . Recent evidence indicates that BFR-enhanced exercise regimens can lead to greater improvements in pain reduction, muscle strength, and quality of life compared to traditional exercise alone in populations with knee osteoarthritis (3). However, the application of BFR training specifically for medial knee pain associated with varus deformity in active adults remains underexplored. This study seeks to address this gap by comparing the efficacy of BFR-enhanced exercises versus standard exercise protocols in this population, potentially offering a more effective rehabilitation strategy.

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Aim:

To investigate the effectiveness of BFR in combination with targeted exercises for active adults with varus deformity and medial knee pain.

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2.4.1- Type of the study:

Randomized controlled trial

2.4.2- Study Setting:

Outpatient

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2.4.3- Study subjects:

1. Inclusion criteria:

■ Age: 30-55 years old

■ BMI: 18-25

■ Presence of medial knee pain

• Mild to moderate Varus deformity confirmed via X-Ray Long Film (2°<HKA≤10°) (4)(4)(5)
• Kellgren and Lawrence system for classification of osteoarthritis (6):

grade 1 (doubtful): doubtful joint space narrowing and possible osteophytic lipping grade 2 (minimal): definite osteophytes and possible joint space narrowing grade 3 (moderate): moderate multiple osteophytes, definite narrowing of joint space, some sclerosis and possible deformity of bone ends

■ Active adults (on Based REFA work classification)

2. Exclusion criteria:

• BMI > 25
• History of knee surgery
• Any contraindication to exercise or BFR (DVT history, uncontrolled hypertension, peripheral vascular disease, pregnancy)
• Other significant musculoskeletal or neurological affecting lower extremity function (hip osteoarthritis, rheumatoid arthritis, peripheral neuropathy)

3. Sample Size Calculation:

G*Power software version 3.1.9.7 was utilized to estimate the required sample size for the present study. A total of 30 participants was calculated to detect a moderate effect size (f = 0.35) using repeated-measures ANOVA for two groups, with an a priori significance level (α) of 0.05 and statistical power (1-β) of 0.80. To accommodate an anticipated attrition rate of 20%, approximately 80 active adults aged 30 to 55 years, with a BMI between 18 and 25, experiencing medial knee pain and confirmed varus deformity by measuring lower limb mechanical axes (<2° and ≤10° in X-Ray Long Film), will be recruited. Screening will be conducted via a detailed medical history questionnaire. Risks, benefits, study commitments, and participant rights will be thoroughly explained, with all questions answered prior to enrolment.

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2.4.4 - Study tools (in detail, e.g., lab methods, instruments, steps, chemicals, …):

○ Participants will be randomly assigned to the intervention and control groups using a computer-generated random sequence, ensuring allocation concealment, and minimizing selection bias.

○ Control Group: Specific Exercise Program (Hip adductors/abductors, internal rotators, and knee extensors) (8&10).

○ BFR Group: Specific Exercise Program with BFR

• BFR Protocol Details: BFR will be applied using a (Smart Tools Plus, LLC, USA) tourniquet system, placed on the proximal thigh. Pressure will be set at 40-80% of limb occlusion pressure (LOP), determined individually. The cuff will be inflated during exercise sets and deflated during rest periods (e.g., 1 minute rest between sets). Participants will be monitored for any signs of adverse events, such as excessive pain, numbness, or discoloration.
• Study Procedures: The study will involve a baseline assessment, a 6-week intervention period, and a follow-up assessment at 12 weeks, 6 months, and 1 year (5). Baseline assessments will include demographics, medical history, NPRS, Oxford Knee Score, LEFS, QoL Measurement, MMT, and X-Ray Long Film.

2.4.5 - Research outcome measures:

Primary:

• Functional: Oxford Knee Score (OKS) baseline, 6 weeks, and at 3-months, 6 months follow-up.

Secondary:

○ Kellgren and Lawrence system for classification of osteoarthritis baseline and at 6 months

○ Functional: Lower Extremity Functional Scale (LEFS) baseline, 6 weeks, and at 3-months, 6 months follow-up

○ Pain: Numerical Pain Rating Scale (NPRS) baseline, 6 weeks, and at 3-months, 6 months follow-up

○ Quality of Life: [SF-36] baseline, 6 weeks, and at 3-months, 6 months follow-up

○ Muscle Strength: Manual Muscle Testing (MMT) for hip Flexors, Internal rotators and Adductors at baseline, 6 weeks follow-up

• Number of relapses in one year follow
• Radiographic Assessment: X-Ray Long Film mechanical axes (to measure varus angle) ■ The Hip Knee Ankle Angle (HKA), Mechanical Lateral Distal Femoral Angle (MLDFA) and Medial Proximal Tibial Angle (MPTA) at baseline and 3-months follow-up.

Data collection:

Data will be collected at baseline, post-intervention 6 weeks, and at 3-months, 6 months follow-up. Outcome measures will be administered by a trained, blinded assessor. Radiographic assessments will be performed by a qualified radiologist. Muscle strength will be measured using VALD handheld dynamometer:

1- Hip Flexors : Standing position and resistance above the knee. 2- Hip Adductors : Supine with fully extended and the resistance above the knee.

Supine with 45 degrees knee flexion and the resistance above the knee. 3- Hip Internal rotators : Sitting position and the resistance is above lateral malleolus.

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Randomization And Blinding:

Participants will be randomly assigned to either the intervention or control group using an alternating allocation method. Specifically, the first enrolled patient will be assigned to the intervention group, the second to the control group, the third to the intervention group, and so on. The therapist responsible for outcome assessment will be blinded to group allocation to reduce measurement bias. However, due to the nature of the treatment, only single blinding is possible, as participants and treating therapists will be aware of the intervention received.

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Statistical tests:

Quantitative variables will present in terms of mean +/-SD and qualitative variables will be expressed as frequency and percentage. Appropriate tests of significance can be used for measured variables. Significance level will be set at 0.05.

Conditions

Medial Knee Pain; Varus Knee Deformity; Knee Osteoarthritis (Mild to Moderate, Medial Compartment)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Control Group - Targeted Exercise Program

Participants in the control group will perform a specific targeted exercise program focusing on hip adductors, abductors, internal rotators, and knee extensors. Exercises will be performed at moderate intensity without any blood flow restriction. The program aims to improve lower limb alignment, muscle balance, and functional performance through conventional strengthening exercises.

Group Type: ACTIVE_COMPARATOR

Targeted Exercise Program

Intervention Type: BEHAVIORAL

A structured therapeutic exercise program designed to strengthen the hip adductors, abductors, internal rotators, and knee extensors. The program focuses on improving muscular balance, lower limb alignment, and functional performance in active adults with medial knee pain and varus deformity. Exercises are performed under therapist supervision at moderate intensity without blood flow restriction. This program serves as the control intervention.

Intervention Group - Blood Flow Restriction (BFR) with Targeted Exercise Program

Participants in the intervention group will perform the same targeted exercise program (hip adductors, abductors, internal rotators, and knee extensors) combined with Blood Flow Restriction (BFR) using a Smart Tools Plus (LLC, USA) pneumatic cuff applied to the proximal thigh.

Cuff pressure will be set individually at 40-80% of limb occlusion pressure (LOP), maintained during exercise sets and released during 1-minute rest intervals. The intervention aims to enhance muscle strength and function while minimizing joint stress and pain.

Group Type: EXPERIMENTAL

Blood Flow Restriction (BFR) Training with Targeted Exercise Program

Intervention Type: DEVICE

Participants perform the same targeted exercise program combined with Blood Flow Restriction (BFR) training using a Smart Tools Plus (LLC, USA) pneumatic cuff system applied to the proximal thigh.

Cuff pressure is individually set at 40-80% of the limb occlusion pressure (LOP), maintained during exercise sets and released during rest intervals (1 minute between sets). The intervention aims to enhance muscle strength and hypertrophy while reducing joint load and pain, providing an effective rehabilitation approach for adults with medial knee pain and varus deformity.

Interventions

Targeted Exercise Program

A structured therapeutic exercise program designed to strengthen the hip adductors, abductors, internal rotators, and knee extensors. The program focuses on improving muscular balance, lower limb alignment, and functional performance in active adults with medial knee pain and varus deformity. Exercises are performed under therapist supervision at moderate intensity without blood flow restriction. This program serves as the control intervention.

Intervention Type: BEHAVIORAL

Blood Flow Restriction (BFR) Training with Targeted Exercise Program

Participants perform the same targeted exercise program combined with Blood Flow Restriction (BFR) training using a Smart Tools Plus (LLC, USA) pneumatic cuff system applied to the proximal thigh.

Cuff pressure is individually set at 40-80% of the limb occlusion pressure (LOP), maintained during exercise sets and released during rest intervals (1 minute between sets). The intervention aims to enhance muscle strength and hypertrophy while reducing joint load and pain, providing an effective rehabilitation approach for adults with medial knee pain and varus deformity.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age between 30 and 55 years
• Body Mass Index (BMI) between 18 and 25
• Presence of medial knee pain
• Mild to moderate varus deformity confirmed via X-Ray Long Film (2° < HKA ≤ 10°) (4)(4)(5)
• Kellgren and Lawrence classification of osteoarthritis (grades 1-3) (6):
• Grade 1 (doubtful): doubtful joint space narrowing and possible osteophytic lipping
• Grade 2 (minimal): definite osteophytes and possible joint space narrowing
• Grade 3 (moderate): moderate multiple osteophytes, definite narrowing of joint space, some sclerosis and possible deformity of bone ends
• Active adults (based on REFA work classification)

Exclusion Criteria

• BMI > 25
• History of knee surgery
• Any contraindication to exercise or BFR, including:
• History of deep vein thrombosis (DVT)
• Uncontrolled hypertension
• Peripheral vascular disease
• Pregnancy
• Other significant musculoskeletal or neurological conditions affecting lower extremity function (e.g., hip osteoarthritis, rheumatoid arthritis, peripheral neuropathy)

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Mariam ibrahim

Physical Therapy Research Fellow, Assiut University, EGYPT

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Faculty of MEdicine, Assiut University

Asyut, , Egypt

Countries

Egypt

References

White WL. Erratum to: Why I hate the index finger. Hand (N Y). 2011 Jun;6(2):233. doi: 10.1007/s11552-011-9321-0. Epub 2011 Mar 18.

Reference Type: BACKGROUND

PMID: 21776199 (View on PubMed)

Other Identifiers

04-2025-300646

Identifier Type: -

Identifier Source: org_study_id