Clinical trial NCT05596591: Focused Extracorporeal Shockwave Therapy for Knee Arthritis
Official title: Focused Extracorporeal Shockwave Therapy for Subchondral Bone Marrow Lesions in People With Knee Osteoarthritis: A Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bone Marrow Edema
Knee Osteoarthritis
Knee Pain Chronic
Keywords: Shockwave Therapy
Lead sponsor: Kessler Foundation
Sponsor class: OTHER
Collaborators: name: New Jersey Regenerative Institute, LLC
First posted: 2022-10-27
Enrollment: 15
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective pilot clinical trial.
Primary purpose: TREATMENT

Brief summary: Subchondral bone marrow lesions (BMLs) in knee osteoarthritis (OA) are strongly associated with presence and severity of knee pain, structural deterioration, disease progression with an increased risk of total knee arthroplasty. OA-related BMLs may regress or resolve within 30 months which could be associated with long lasting disability. It has been reported that BMLs persist in the majority of knee OA patients. Different treatment strategies have been proposed including rest and protected weight-bearing, bisphosphonates, subchondroplasty and intraosseous orthobiologic injection. However, conservative treatment response takes a long time and other interventions may be considered invasive procedures that show varying results with several side effects. Focused extracorporeal shockwave therapy (f-ESWT) has been established as a safe non-invasive treatment with positive results in different bone disorders that share the same pathological features of BMLs. This is an exploratory, randomized-controlled, pilot study to determine the efficacy and safety of f-ESWT compared to the standard-of-care (analgesics and protected weight bearing) for the treatment of BMLs in patients with knee OA. Thirty subjects with knee OA who have history of knee pain at rest and during walking with the confirmed diagnosis of subchondral BML(s) on magnetic resonance imaging (MRI) despite at least 4 weeks of conservative treatment will be enrolled into this study. Subjects will receive a total of 4 sessions (at high energy level) over 4 consecutive weeks. Participants will be evaluated for adverse events and changes in pain intensity and knee function, using an 11-point numerical rating scale (NRS; 0-10, with anchors "no pain" and "pain as bad as you can imagine") and; the Knee injury and Osteoarthritis Outcome Score, respectively. Subjects will be assessed with these outcome measures at baseline, 1 month, 2 months, 3 months, and 6 months after the treatment. MRI of the involved knee will be performed prior to treatment (baseline) and 3 months and 6 months after treatment.

Detailed description: Background: Subchondral bone marrow lesions (BMLs) in knee osteoarthritis (OA) are strongly associated with presence and severity of knee pain, structural deterioration, disease progression with an increased risk of total knee arthroplasty. OA-related BMLs may regress or resolve within 30 months which could be associated with long lasting disability. It has been reported that BMLs persist in the majority of people with knee OA. Different treatment strategies have been proposed including rest and protected weight-bearing, bisphosphonates, subchondroplasty and intraosseous orthobiologic injection. However, conservative treatment response takes a long time and other interventions may be considered invasive procedures that show varying results with several side effects. Focused extracorporeal shockwave therapy (f-ESWT) has been established as a safe non-invasive treatment with positive results in different bone disorders that share the same pathological features of BMLs.

Objective: This is an exploratory pilot study to determine the efficacy and safety of f-ESWT for the treatment of BMLs in people with knee OA.

Participants: Fifteen subjects with knee OA who have history of knee pain at rest and during walking with the confirmed diagnosis of subchondral BML(s) on magnetic resonance imaging (MRI) despite at least 4 weeks of conservative treatment will be enrolled into this study.

Procedures: Subjects will receive a total of 4 focused ESWT sessions (at high energy level) over 4 consecutive weeks.

Outcome Measures: Participants will be evaluated for adverse events and changes in pain intensity and knee function, using an 11-point numerical rating scale (NRS; 0-10, with anchors "no pain" and "pain as bad as you can imagine") and; the Knee injury and Osteoarthritis Outcome Score (KOOS; five subscales: pain, other symptoms, function in activities of daily living, function in sports and recreation, and knee-related quality of life), respectively. Subjects will be assessed with these outcome measures at baseline, 1 month, 2 months, 3 months, and 6 months after the treatment. MRI of the involved knee will be performed prior to treatment (baseline) and 3 months and 6 months after treatment.

Anticipated Outcomes: Focused extracorporeal shockwave therapy is a safe alternative to treating BMLs and will significantly decrease knee pain intensity and improve function in people with knee OA- related BMLs.

Eligibility criteria: Inclusion Criteria:

1. Males and females 30-80 years old, inclusive.
2. Kellgren-Lawrence (KL) score grade 2-4 as diagnosed on X-Ray.
3. Presence of BML(s) on MRI in a weight-bearing region of the knee (medial/lateral femoral condyle or tibial plateau).
4. Knee pain for more than 2 months.
5. Knee pain intensity during the week leading up to the screening visit is at least 4 out of 10 on an 11-point numerical rating scale (NRS; 0, no pain; 10, maximum pain imaginable).
6. Patient pain confined to the same compartment as the BML(s).
7. Subjects would have failed a minimum of 4 weeks of conservative treatment including rest, analgesics, limited weight-bearing with or without an assistive device.

Exclusion Criteria:

1. Traumatic BMLs.
2. Primary cause of patient pain and loss of function is due to pathology other than BML(s), according to patient history and clinical evaluation.
3. Presence of bilateral BML(s).
4. Systemic autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis.
5. Participants receiving glucocorticoids due to any other underlying disease.
6. Prior treatment for BMLs including:

   1. Subchondroplasty in the involved knee.
   2. Intraosseous and/or intra-articular injection of orthobiologics in the past 6 months, such as platelet rich plasma (PRP), bone marrow aspirate concentrates, micro-fragmented adipose tissue (MFAT) or stromal vascular fraction.
7. Prior use of bisphosphonates, except according to the washout schedule:

   1. 2 years (if use \> 48 weeks).
   2. 1 year (if used \> 8 weeks but \< 48 weeks)
   3. 6 months (if used \> 2 weeks but \< 8 weeks)
   4. 2 months (if used \< 2 weeks)
   5. Any intravenous bisphosphonate within the prior 2 years.
8. Intra-articular steroid injection in the prior 3 months.
9. Previous knee surgery in the past 6 months.
10. Tumors
11. Infection or fracture on ipsilateral lower limb.
12. Pregnancy.
13. Contraindications to f-ESWT, such as severe coagulopathy, malignant tumor in the treatment area.
14. Contraindications to MRI scanning including:

    * Presence of metal implants such as implanted pacemaker, metal sutures, metallic protheses (including metal pins and rods, heart valves), presence of shrapnel or iron filings in the eye, magnetic dental implants, cochlear implants, cerebral aneurysm clip, and deep brain stimulator.
    * Claustrophobia.
    * The patient has been informed by his/her doctor that it is medically unsafe to receive regular MRI as part of his/her medical care.

Primary outcomes:
measure: Change in knee pain numerical rating scale scores
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in knee pain numerical rating scale scores
timeFrame: 8 weeks
measure: Change in knee pain numerical rating scale scores
timeFrame: 24 weeks
measure: Change in Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: 8 weeks
measure: Change in Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: 12 weeks
measure: Change in Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: 24 weeks
measure: Change in bone marrow lesion area
timeFrame: 12 weeks
measure: Change in bone marrow lesion area
timeFrame: 24 weeks
measure: Change in whole-organ MRI scoring (WORMS)-Subchondral bone scale
timeFrame: 12 weeks
measure: Change in whole-organ MRI scoring (WORMS)-Subchondral bone scale
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Cedar Knolls
country: United States
facility: New Jersey Regenerative Institute
state: New Jersey
city: West Orange
country: United States
facility: Nathan Hogaboom
state: New Jersey
Study officials:
References: