Clinical trial NCT05617911: Clinical Comparison of Patellofemoral Pain Syndrome Outcomes After Blood Flow Restriction Therapy
Official title: Clinical Comparison of Patellofemoral Pain Syndrome Outcomes After Blood Flow Restriction Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Patellofemoral Pain Syndrome
Anterior Knee Pain Syndrome
Keywords: Blood Flow Restriction
Patellofemoral Pain Syndrome
Physical Therapy
Non-Specific Anterior Knee Pain
Lead sponsor: Gaylord Hospital, Inc
Sponsor class: OTHER
Collaborators: name: UConn Health
First posted: 2022-11-16
Enrollment: 1
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if Blood Flow Restriction therapy improves patient related outcomes in those diagnosed with Patellofemoral Pain Syndrome compared to those in the sham comparator control group.

Detailed description: Patellofemoral Pain Syndrome (PFPS), also known as Non-Specific Anterior Knee Pain (AKP), is a non-specific musculoskeletal condition characterized by loss of function and pain localized to the patella. PFPS affects up to 22% of the general population yearly, with females affected more so than males. Adolescents (28%, mixed gender) and elite athletes (up to 35% in knee dominant sports such as cycling) are also commonly affected, making this a relatively widespread condition. Additionally, PFPS has a generally unfavorable prognosis, with up to 40% of individuals failing conservative treatment after 1 year, and 57% reporting continued symptoms for 5 to 8-years following. Higher levels of baseline disability and longer duration of symptoms lead to an even poorer prognosis, making early recognition and novel treatments key. To complicate things further, the presence of negative psychosocial factors is commonly found in this population and may be a greater predictor of outcomes than physical ones.

Previously, biomechanical factors, such as maltracking of the patella and chondromalacia, have been called into question as potential causes of PFPS symptoms. However, both are now thought to be potential consequences of having PFPS. That being said, PFPS is generally accepted as a non-specific condition as there may be a number of different structures implicated as potential nociceptive drivers, and determining the exact tissue does not seem to be important to overall management strategies. This finding, in connection with the high prevalence of negative psychosocial factors, points less to a physiologically driven condition, and more towards a pain driven condition. While this theoretically makes diagnosing and treatment selection more ubiquitous, there does not seem to be a clear treatment strategy that works best for all patients. Despite a clear biomechanical cause, adjusting exercise selection or technique to include different loads and forces on the patella is still warranted based on patient presentation. For example, during open chain knee extension, the lowest loads are placed on the patella between 90- and 45-degree flexion, and open chain between 0 and 60 degrees. People with PFPS often benefit from adjusting the exercise selection, technique and load.

Recent research compared multiple different exercise strategies (combined core and hip work, knee work only, and open vs closed-chain), without any one program showing significant advantage over the others. A combination of these approaches may be best. One theme within PFPS exercise research that appears consistent is the high level of sensitivity and poor response to treatment where higher levels of pain are present. This is in contrast to tendon related pain, such as patellar tendinopathy, where working into moderate levels of pain seems to be helpful for outcomes.

The main mechanism driving improvements following exercise therapy for PFPS is not hypertrophy, but rather thought to be exercise induced hypoalgesia. This is a phenomenon where performing both acute bouts, as well as regular exercise (aerobic and resistance), reduces pain both in the short and long terms. Since exercise seems to reduce pain in both local and distant sites of the exercising area, it is thought to provide both local and systemic pain reducing effects. The magnitude and duration of the exercise seems to play an important role as well, with higher intensity and longer durations of exercising producing greater effects.

Since patients with PFPS are unable to achieve these desired parameters, alternative strategies need to be investigated. Two options may be blood flow restriction (BFR) therapy and low load training to failure, both of which may capture some of the hypoalgesic effects while minimizing AKP. BFR involves the application of an external device to reduce arterial blood flow to the exercising area, while largely occluding venous return from that same area. Exercise intensities generally range from 20-30% of the patients' 1 repetition maximum (1RM) weight, with relatively high repetitions (sometimes to failure); this is opposed to traditional resistance training at 70%+ of 1RM. BFR training has been demonstrated to amplify the effects of exercise induced hypoalgesia (in addition to a host of other physiological benefits) through unconfirmed mechanisms. Leading theories suggest that the lack of available oxygen to the exercising area may lead to: the activation of the endogenous opioid and cannabinoid systems; systemic changes to the cardiovascular system; or increased number of metabolites such as hydrogen ions and lactic acid, which may also be contributing factors.

Clinical research on the application of BFR in patients with PFPS has been both limited and mixed, with only two trials having been conducted in this area. One study from 2017 looked at high-load with BFR placebo, versus low-load BFR with leg press and knee extensions. Only the high-load group showed a modest medium-term effect on pain, lowering it for \~24 hours after BFR over the training period. The other paper from 2022 included both knee and hip strengthening exercises, comparing a low-load BFR group versus a high-load training group with no placebo; of note, the programs were not equated in terms of exercises completed. In this study, no significant difference was observed between groups. To date, there have been limited to no sham arms in studies where a BFR cuff was used. Given the potential for placebo effects, this was an important consideration in the design of the study.

Given the heterogeneity of these two studies, and the paucity of research in this area, the aim of the current study is to compare a low load training to failure (with BFR placebo) to low load BFR training to failure on the effect of pain related outcomes, function, strength and other measures. We hypothesize that BFR training will improve objective and subjective outcomes in patients with patellofemoral pain syndrome (PFPS) more than standard therapy with a sham BFR cuff.

Research aim 1: Determine whether the use of BFR improves patient-perceived function through a series of subjective patient-reported outcome measurements (PROs) throughout long-term recovery compared to patients in the sham control group. While we anticipate both groups may show improvement over time, we hypothesize that patients using BFR and the prescribed physical therapy protocol will demonstrate significantly improved PRO scores compared to the sham control group. These PROs include the Lower Extremity Functional Scale (LEFS), Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain (KOOS-PF), the Single Assessment Numerical Evaluation (SANE), the Fear Avoidance Beliefs Questionnaire (FABQ), and Numerical Rating Scale (NRS) Pain Scale 1-10. Participants will be asked to complete PRO at the start of physical therapy (i.e. baseline), 4-weeks, 9-weeks or patient discharge if it is before the scheduled 9-week assessment, 6-month, and 12-month timepoints.

Research aim 2: Determine whether the use of BFR improves objective outcome measurements throughout prescribed physical therapy sessions compared to patients in the control group. While we anticipate both groups may show improvement over time, we hypothesize that patients using BFR and the prescribed physical therapy protocol will demonstrate significantly improved quadriceps isometric strength over the sham control group. Outcomes will be measured at the start of the physical therapy (i.e. baseline), 4-weeks, and 9-weeks or patient discharge if it is before the scheduled 9-week assessment.

Eligibility criteria: Inclusion Criteria:

Diagnosis of patellofemoral pain syndrome (PFPS) or non-specific anterior knee pain (NSAKP) and plan to attend Gaylord Specialty Healthcare Physical Therapy

Exclusion Criteria:

Member of a defined vulnerable population, women who are or suspected to be pregnant, prisoners, children under 15, or other protected populations

Body mass of the leg preventing the cuff from fitting properly

Radiographic evidence of osteoarthritis (≥ Kellgren-Lawrence Grade 2)

History of intra-articular injection into either knee within 3 -months

Uncontrolled or untreated inflammatory disorder

Acute inflammatory disorder

Uncontrolled Diabetes and/or peripheral neuropathy, impaired circulation

Uncontrolled cardiac conditions including uncontrolled hypertension

Areas of thrombophlebitis, thrombosis

Distal wounds or pain below the knee \>4/10

History of or current rhabdomyolysis

Prolonged immobilization (\>3 months)

Sickle cell anemia

Lymphadenectomy

Varicose veins, or a history of personal or immediate family history (parental or sibling) of deep vein thrombosis

Current infection at or below the level of cuff placement

Malignancies in or below the area to be treated

Other conditions/medications that would interfere with subject safety or data collection in the opinion of the PI

Subjects with an increased risk of non-response as determined by the therapist

Once entered in the study, a diagnosis change that affects participation

Primary outcomes:
measure: Numeric Pain Rating Scale: Enrollment
timeFrame: This assessment will be collected upon enrollment in the study.
measure: Numeric Pain Rating Scale: 1 Week
timeFrame: This assessment will be collected 1-week into treatment
measure: Numeric Pain Rating Scale: 4 Weeks
timeFrame: This assessment will be collected 4-weeks into treatment.
measure: Numeric Pain Rating Scale: 9 Weeks/Discharge
timeFrame: This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.
measure: Numeric Pain Rating Scale: 6 Months
timeFrame: This assessment will be collected 6 months post start date.
measure: Numeric Pain Rating Scale: 12 Months
timeFrame: This assessment will be collected 12 months post start date.
measure: Lower Extremity Functional Scale: Enrollment
timeFrame: This assessment will be collected upon enrollment in the study.
measure: Lower Extremity Functional Scale: 1 Week
timeFrame: This assessment will be collected 1-week into treatment.
measure: Lower Extremity Functional Scale: 4 Weeks
timeFrame: This assessment will be collected 4-weeks into treatment.
measure: Lower Extremity Functional Scale: 9 Weeks/Discharge
timeFrame: This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.
measure: Lower Extremity Functional Scale: 6 Months
timeFrame: This assessment will be collected 6 months post start date.
measure: Lower Extremity Functional Scale: 12 Months
timeFrame: This assessment will be collected 12 months post start date.
measure: Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: Enrollment
timeFrame: This assessment will be collected upon enrollment in the study.
measure: Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: 1 Week
timeFrame: This assessment will be collected1-week into treatment.
measure: Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: 4 Weeks
timeFrame: This assessment will be collected 4-weeks into treatment.
measure: Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: 9 Weeks/Discharge
timeFrame: This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.
measure: Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: 6 Months
timeFrame: This assessment will be collected 6 months post start date.
measure: Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: 12 Months
timeFrame: This assessment will be collected 12 months post start date.
measure: Single Assessment Numerical Evaluation: Enrollment
timeFrame: This assessment will be collected upon enrollment in the study.
measure: Single Assessment Numerical Evaluation: 1 Week
timeFrame: This assessment will be collected 1-week into treatment.
measure: Single Assessment Numerical Evaluation: 4 Weeks
timeFrame: This assessment will be collected 4-weeks into treatment.
measure: Single Assessment Numerical Evaluation: 9 Weeks/Discharge
timeFrame: This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.
measure: Single Assessment Numerical Evaluation: 6 Months
timeFrame: This assessment will be collected 6 months post start date.
measure: Single Assessment Numerical Evaluation: 12 Months
timeFrame: This assessment will be collected 12 months post start date.
measure: Tenger Activity Scale: Enrollment
timeFrame: This assessment will be collected upon enrollment.
measure: Tenger Activity Scale: 6 Months
timeFrame: This assessment will be collected 6 months post start date.
measure: Tenger Activity Scale: 12 Months
timeFrame: This assessment will be collected 12 months post start date.
measure: Fear Avoidance Beliefs Questionnaire: Enrollment
timeFrame: This assessment will be collected upon enrollment in the study.
measure: Fear Avoidance Beliefs Questionnaire: 1 Week
timeFrame: This assessment will be collected 1-week into treatment.
measure: Fear Avoidance Beliefs Questionnaire: 4 Weeks
timeFrame: This assessment will be collected 4-weeks into treatment.
measure: Fear Avoidance Beliefs Questionnaire: 9 Weeks/Discharge
timeFrame: This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.
measure: Fear Avoidance Beliefs Questionnaire: 6 Months
timeFrame: This assessment will be collected 6 months post start date.
measure: Fear Avoidance Beliefs Questionnaire: 12 Months
timeFrame: This assessment will be collected 12 months post start date.
Secondary outcomes:
measure: Quadricep Isometric Strength: Enrollment
timeFrame: This assessment will be collected upon enrollment in the study.
measure: Quadricep Isometric Strength: 1 Week
timeFrame: This assessment will be collected 1-week into treatment.
measure: Quadricep Isometric Strength: 4 Weeks
timeFrame: This assessment will be collected 4-weeks into treatment.
measure: Quadricep Isometric Strength: 9 Weeks/Discharge
timeFrame: This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.
Other outcomes:
Locations:
city: Cheshire
country: United States
facility: Gaylord Specialty Healthcare Outpatient Physical Therapy; Cheshire
state: Connecticut
city: Cromwell
country: United States
facility: Gaylord Specialty Healthcare Outpatient Physical Therapy; Cromwell
state: Connecticut
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Madison
country: United States
facility: Gaylord Specialty Healthcare Outpatient Physical Therapy; Madison
state: Connecticut
city: Wallingford
country: United States
facility: Gaylord Hospital
state: Connecticut
city: Wallingford
country: United States
facility: Gaylord Specialty Healthcare Outpatient Physical Therapy; Wallingford
state: Connecticut
Study officials:
affiliation: Physical Therapist
name: Eric Sokolowski
role: PRINCIPAL_INVESTIGATOR
affiliation: Physical Therapist
name: Danielle Letendre
role: PRINCIPAL_INVESTIGATOR
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