Clinical Comparison of Patellofemoral Pain Syndrome Outcomes After Blood Flow Restriction Therapy

Patellofemoral Pain Syndrome Clinical Trial

Official title:

Clinical Comparison of Patellofemoral Pain Syndrome Outcomes After Blood Flow Restriction Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05617911
• Other study ID #: 202209SOK
• Status: Terminated
• Phase: N/A
• Start date: November 15, 2022
• Est. completion date: October 10, 2023

Study information

• Verified date: October 2023
• Source: Gaylord Hospital, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: October 10, 2023
• Est. primary completion date: October 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anterior Knee Pain Syndrome
• Patellofemoral Pain Syndrome
• Somatoform Disorders
• Syndrome

Intervention

Device:
• Blood Flow Restriction Cuff
Blood Flow Restriction (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.

Procedure:
• Sham and standard of Care Therapy
SoC PT + non-inflated BFR cuff

Locations

Country	Name	City	State
United States	Gaylord Specialty Healthcare Outpatient Physical Therapy; Cheshire	Cheshire	Connecticut
United States	Gaylord Specialty Healthcare Outpatient Physical Therapy; Cromwell	Cromwell	Connecticut
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Gaylord Specialty Healthcare Outpatient Physical Therapy; Madison	Madison	Connecticut
United States	Gaylord Hospital	Wallingford	Connecticut
United States	Gaylord Specialty Healthcare Outpatient Physical Therapy; Wallingford	Wallingford	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Gaylord Hospital, Inc	UConn Health

Country where clinical trial is conducted

United States, 

References & Publications (18)

Brightwell BD, Stone A, Li X, Hardy P, Thompson K, Noehren B, Jacobs C. Blood flow Restriction training After patellar INStability (BRAINS Trial). Trials. 2022 Jan 28;23(1):88. doi: 10.1186/s13063-022-06017-1. — View Citation

Collins NJ, Barton CJ, van Middelkoop M, Callaghan MJ, Rathleff MS, Vicenzino BT, Davis IS, Powers CM, Macri EM, Hart HF, de Oliveira Silva D, Crossley KM. 2018 Consensus statement on exercise therapy and physical interventions (orthoses, taping and manual therapy) to treat patellofemoral pain: recommendations from the 5th International Patellofemoral Pain Research Retreat, Gold Coast, Australia, 2017. Br J Sports Med. 2018 Sep;52(18):1170-1178. doi: 10.1136/bjsports-2018-099397. Epub 2018 Jun 20. — View Citation

Collins NJ, Bierma-Zeinstra SM, Crossley KM, van Linschoten RL, Vicenzino B, van Middelkoop M. Prognostic factors for patellofemoral pain: a multicentre observational analysis. Br J Sports Med. 2013 Mar;47(4):227-33. doi: 10.1136/bjsports-2012-091696. Epub 2012 Dec 13. — View Citation

Constantinou A, Mamais I, Papathanasiou G, Lamnisos D, Stasinopoulos D. Comparing hip and knee focused exercises versus hip and knee focused exercises with the use of blood flow restriction training in adults with patellofemoral pain. Eur J Phys Rehabil Med. 2022 Apr;58(2):225-235. doi: 10.23736/S1973-9087.22.06691-6. Epub 2022 Jan 5. — View Citation

Dolak KL, Silkman C, Medina McKeon J, Hosey RG, Lattermann C, Uhl TL. Hip strengthening prior to functional exercises reduces pain sooner than quadriceps strengthening in females with patellofemoral pain syndrome: a randomized clinical trial. J Orthop Sports Phys Ther. 2011 Aug;41(8):560-70. doi: 10.2519/jospt.2011.3499. Epub 2011 Jun 7. Erratum In: J Orthop Sports Phys Ther. 2011 Sep;41(9):700. — View Citation

Giles L, Webster KE, McClelland J, Cook JL. Quadriceps strengthening with and without blood flow restriction in the treatment of patellofemoral pain: a double-blind randomised trial. Br J Sports Med. 2017 Dec;51(23):1688-1694. doi: 10.1136/bjsports-2016-096329. Epub 2017 May 12. — View Citation

Hughes L, Patterson SD. The effect of blood flow restriction exercise on exercise-induced hypoalgesia and endogenous opioid and endocannabinoid mechanisms of pain modulation. J Appl Physiol (1985). 2020 Apr 1;128(4):914-924. doi: 10.1152/japplphysiol.00768.2019. Epub 2020 Feb 27. — View Citation

Kountouris A, Cook J. Rehabilitation of Achilles and patellar tendinopathies. Best Pract Res Clin Rheumatol. 2007 Apr;21(2):295-316. doi: 10.1016/j.berh.2006.12.003. — View Citation

Lankhorst NE, van Middelkoop M, Crossley KM, Bierma-Zeinstra SM, Oei EH, Vicenzino B, Collins NJ. Factors that predict a poor outcome 5-8 years after the diagnosis of patellofemoral pain: a multicentre observational analysis. Br J Sports Med. 2016 Jul;50(14):881-6. doi: 10.1136/bjsports-2015-094664. Epub 2015 Oct 13. — View Citation

Maclachlan LR, Matthews M, Hodges PW, Collins NJ, Vicenzino B. The psychological features of patellofemoral pain: a cross-sectional study. Scand J Pain. 2018 Apr 25;18(2):261-271. doi: 10.1515/sjpain-2018-0025. — View Citation

Misra G, Paris TA, Archer DB, Coombes SA. Dose-response effect of isometric force production on the perception of pain. PLoS One. 2014 Feb 4;9(2):e88105. doi: 10.1371/journal.pone.0088105. eCollection 2014. — View Citation

Post WR, Dye SF. Patellofemoral Pain: An Enigma Explained by Homeostasis and Common Sense. Am J Orthop (Belle Mead NJ). 2017 Mar/Apr;46(2):92-100. — View Citation

Powers CM, Ho KY, Chen YJ, Souza RB, Farrokhi S. Patellofemoral joint stress during weight-bearing and non-weight-bearing quadriceps exercises. J Orthop Sports Phys Ther. 2014 May;44(5):320-7. doi: 10.2519/jospt.2014.4936. Epub 2014 Mar 27. — View Citation

Saltychev M, Dutton RA, Laimi K, Beaupre GS, Virolainen P, Fredericson M. Effectiveness of conservative treatment for patellofemoral pain syndrome: A systematic review and meta-analysis. J Rehabil Med. 2018 May 8;50(5):393-401. doi: 10.2340/16501977-2295. — View Citation

Sisk D, Fredericson M. Update of Risk Factors, Diagnosis, and Management of Patellofemoral Pain. Curr Rev Musculoskelet Med. 2019 Dec;12(4):534-541. doi: 10.1007/s12178-019-09593-z. — View Citation

Smith BE, Selfe J, Thacker D, Hendrick P, Bateman M, Moffatt F, Rathleff MS, Smith TO, Logan P. Incidence and prevalence of patellofemoral pain: A systematic review and meta-analysis. PLoS One. 2018 Jan 11;13(1):e0190892. doi: 10.1371/journal.pone.0190892. eCollection 2018. — View Citation

Song JS, Spitz RW, Yamada Y, Bell ZW, Wong V, Abe T, Loenneke JP. Exercise-induced hypoalgesia and pain reduction following blood flow restriction: A brief review. Phys Ther Sport. 2021 Jul;50:89-96. doi: 10.1016/j.ptsp.2021.04.005. Epub 2021 Apr 23. — View Citation

Thiebaud RS, Yasuda T, Loenneke JP, Abe T. Effects of low-intensity concentric and eccentric exercise combined with blood flow restriction on indices of exercise-induced muscle damage. Interv Med Appl Sci. 2013 Jun;5(2):53-9. doi: 10.1556/IMAS.5.2013.2.1. Epub 2013 Jul 4. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numeric Pain Rating Scale: Enrollment	The Numeric Pain Rating Scale is one question pain intensity scale that assesses the current, best, and worst pain level in the last 24 hours	This assessment will be collected upon enrollment in the study.
Primary	Numeric Pain Rating Scale: 1 Week	The Numeric Pain Rating Scale is one question pain intensity scale that assesses the current, best, and worst pain level in the last 24 hours	This assessment will be collected 1-week into treatment
Primary	Numeric Pain Rating Scale: 4 Weeks	The Numeric Pain Rating Scale is one question pain intensity scale that assesses the current, best, and worst pain level in the last 24 hours	This assessment will be collected 4-weeks into treatment.
Primary	Numeric Pain Rating Scale: 9 Weeks/Discharge	The Numeric Pain Rating Scale is one question pain intensity scale that assesses the current, best, and worst pain level in the last 24 hours	This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.
Primary	Numeric Pain Rating Scale: 6 Months	The Numeric Pain Rating Scale is one question pain intensity scale that assesses the current, best, and worst pain level in the last 24 hours	This assessment will be collected 6 months post start date.
Primary	Numeric Pain Rating Scale: 12 Months	The Numeric Pain Rating Scale is one question pain intensity scale that assesses the current, best, and worst pain level in the last 24 hours	This assessment will be collected 12 months post start date.
Primary	Lower Extremity Functional Scale: Enrollment	The LEFS is a 20 question survey that is a valid PROM used for the measurement of lower extremity function based on the patients' initial function, ongoing progress, and long-term outcome	This assessment will be collected upon enrollment in the study.
Primary	Lower Extremity Functional Scale: 1 Week	The LEFS is a 20 question survey that is a valid PROM used for the measurement of lower extremity function based on the patients' initial function, ongoing progress, and long-term outcome	This assessment will be collected 1-week into treatment.
Primary	Lower Extremity Functional Scale: 4 Weeks	The LEFS is a 20 question survey that is a valid PROM used for the measurement of lower extremity function based on the patients' initial function, ongoing progress, and long-term outcome	This assessment will be collected 4-weeks into treatment.
Primary	Lower Extremity Functional Scale: 9 Weeks/Discharge	The LEFS is a 20 question survey that is a valid PROM used for the measurement of lower extremity function based on the patients' initial function, ongoing progress, and long-term outcome	This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.
Primary	Lower Extremity Functional Scale: 6 Months	The LEFS is a 20 question survey that is a valid PROM used for the measurement of lower extremity function based on the patients' initial function, ongoing progress, and long-term outcome	This assessment will be collected 6 months post start date.
Primary	Lower Extremity Functional Scale: 12 Months	The LEFS is a 20 question survey that is a valid PROM used for the measurement of lower extremity function based on the patients' initial function, ongoing progress, and long-term outcome	This assessment will be collected 12 months post start date.
Primary	Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: Enrollment	The KOOS-PF is an 11 question survey that is used to assess five outcomes; they include knee related Quality of Life, activities of daily living, sport and recreation function, activities, pain and symptoms	This assessment will be collected upon enrollment in the study.
Primary	Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: 1 Week	The KOOS-PF is an 11 question survey that is used to assess five outcomes; they include knee related Quality of Life, activities of daily living, sport and recreation function, activities, pain and symptoms	This assessment will be collected1-week into treatment.
Primary	Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: 4 Weeks	The KOOS-PF is an 11 question survey that is used to assess five outcomes; they include knee related Quality of Life, activities of daily living, sport and recreation function, activities, pain and symptoms	This assessment will be collected 4-weeks into treatment.
Primary	Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: 9 Weeks/Discharge	The KOOS-PF is an 11 question survey that is used to assess five outcomes; they include knee related Quality of Life, activities of daily living, sport and recreation function, activities, pain and symptoms	This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.
Primary	Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: 6 Months	The KOOS-PF is an 11 question survey that is used to assess five outcomes; they include knee related Quality of Life, activities of daily living, sport and recreation function, activities, pain and symptoms	This assessment will be collected 6 months post start date.
Primary	Knee Injury and Osteoarthritis Outcome Score for Patellofemoral Pain: 12 Months	The KOOS-PF is an 11 question survey that is used to assess five outcomes; they include knee related Quality of Life, activities of daily living, sport and recreation function, activities, pain and symptoms	This assessment will be collected 12 months post start date.
Primary	Single Assessment Numerical Evaluation: Enrollment	The SANE is a two item questionnaire used globally to assess function	This assessment will be collected upon enrollment in the study.
Primary	Single Assessment Numerical Evaluation: 1 Week	The SANE is a two item questionnaire used globally to assess function	This assessment will be collected 1-week into treatment.
Primary	Single Assessment Numerical Evaluation: 4 Weeks	The SANE is a two item questionnaire used globally to assess function	This assessment will be collected 4-weeks into treatment.
Primary	Single Assessment Numerical Evaluation: 9 Weeks/Discharge	The SANE is a two item questionnaire used globally to assess function	This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.
Primary	Single Assessment Numerical Evaluation: 6 Months	The SANE is a two item questionnaire used globally to assess function	This assessment will be collected 6 months post start date.
Primary	Single Assessment Numerical Evaluation: 12 Months	The SANE is a two item questionnaire used globally to assess function	This assessment will be collected 12 months post start date.
Primary	Tenger Activity Scale: Enrollment	The Tenger Activity Scale aims to provide a standardized method in determining the level of activity prior to injury and level of activity post injury that can be documented on a numerical scale.	This assessment will be collected upon enrollment.
Primary	Tenger Activity Scale: 6 Months	The Tenger Activity Scale aims to provide a standardized method in determining the level of activity prior to injury and level of activity post injury that can be documented on a numerical scale.	This assessment will be collected 6 months post start date.
Primary	Tenger Activity Scale: 12 Months	The Tenger Activity Scale aims to provide a standardized method in determining the level of activity prior to injury and level of activity post injury that can be documented on a numerical scale.	This assessment will be collected 12 months post start date.
Primary	Fear Avoidance Beliefs Questionnaire: Enrollment	The Fear Avoidance Belief Questionnaire is a 16 question likert scale questionnaire aimed at assessing how everyday activities assess the patient's current level of pain	This assessment will be collected upon enrollment in the study.
Primary	Fear Avoidance Beliefs Questionnaire: 1 Week	The Fear Avoidance Belief Questionnaire is a 16 question likert scale questionnaire aimed at assessing how everyday activities assess the patient's current level of pain	This assessment will be collected 1-week into treatment.
Primary	Fear Avoidance Beliefs Questionnaire: 4 Weeks	The Fear Avoidance Belief Questionnaire is a 16 question likert scale questionnaire aimed at assessing how everyday activities assess the patient's current level of pain	This assessment will be collected 4-weeks into treatment.
Primary	Fear Avoidance Beliefs Questionnaire: 9 Weeks/Discharge	The Fear Avoidance Belief Questionnaire is a 16 question likert scale questionnaire aimed at assessing how everyday activities assess the patient's current level of pain	This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.
Primary	Fear Avoidance Beliefs Questionnaire: 6 Months	The Fear Avoidance Belief Questionnaire is a 16 question likert scale questionnaire aimed at assessing how everyday activities assess the patient's current level of pain	This assessment will be collected 6 months post start date.
Primary	Fear Avoidance Beliefs Questionnaire: 12 Months	The Fear Avoidance Belief Questionnaire is a 16 question likert scale questionnaire aimed at assessing how everyday activities assess the patient's current level of pain	This assessment will be collected 12 months post start date.
Secondary	Quadricep Isometric Strength: Enrollment	Quadricep Isometric Strength is the amount of strength shown in a patient's quadricep muscle via isometric dynomometry	This assessment will be collected upon enrollment in the study.
Secondary	Quadricep Isometric Strength: 1 Week	Quadricep Isometric Strength is the amount of strength shown in a patient's quadricep muscle via isometric dynomometry	This assessment will be collected 1-week into treatment.
Secondary	Quadricep Isometric Strength: 4 Weeks	Quadricep Isometric Strength is the amount of strength shown in a patient's quadricep muscle via isometric dynomometry	This assessment will be collected 4-weeks into treatment.
Secondary	Quadricep Isometric Strength: 9 Weeks/Discharge	Quadricep Isometric Strength is the amount of strength shown in a patient's quadricep muscle via isometric dynomometry	This assessment will be collected 9-weeks into treatment or at discharge, whatever comes first.