Arthritis, Osteoarthritis, Osteoarthritis, Knee, Osteo Arthritis Knee
Conditions
Keywords
Embolotherapy
Brief summary
The need for exploration of more definitive and cost effective non-arthroplasty treatments of osteoarthritis (OA) has been demonstrated by the orthopedic and health economic research. Embolotherapy of neovessels associated with OA joints has been shown to be promising in patients with knee OA. There is a need for level one evidence drawn from randomized clinical trials to prove the safety, feasibility and efficacy of knee embolotherapy compared to standard of care. This randomized pilot study will assign 10 patients with mild-moderate OA to undergo geniculate artery embolization plus standard of care (defined in this study as: physical therapy and oral anti-inflammatory medications, with a maximum of 1 joint injection at the time of enrollment) and 10 patients to receive only medical standard of care (also having had a maximum of 1 joint injection prior to enrollment). The goal of this pilot study is to obtain preliminary estimates of safety and efficacy of embolotherapy to provide sustained symptom control and modify disease progression in patients with mild to moderate knee OA.
Detailed description
This is a single center, two-arm, open label, pilot study to assess feasibility and safety and obtain a preliminary estimate of efficacy of geniculate artery embolization in reducing pain compared to a control group undergoing conservative presurgical management. The 20 patients will be randomly divided into two groups of 10 in 1:1 allocation. One group will have embolization of the geniculate artery branches and standard of care while the other will have only the standard care. Following the completion of the 10 participants in each arm, a safety and data review will be undertaken (Visit 4 in the GAE group and Visit 2 of the SOC). The data will be assessed regarding the trends between the groups as they relate to KOOS/WOMAC pain scale, MRI / Xray evaluation of OA, and presence of inflammatory biomarkers.
Interventions
All patients within the embolization group will undergo unilateral angiography and embolization of the appropriate treatment limb geniculate arteries. For patients with bilateral disease the more clinically symptomatic side will be chosen as the treatment/control knee.
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Between 40 - 70 years of age. * Unilaterally dominant symptomatic OA (bilateral radiographic OA will not exclude). * Symptomatically refractory of at least 3 months of medical and/or rehabilitation measures (anti-inflammatory drugs, and/or physical therapy, and/or strength conditioning, and/or intra-articular injections of the affected knee in the last 3 months). * Kellgren-Lawrence grade 1, 2, or 3 on radiograph of the knee * Willing to comply with the protocol requirements and willing to undergo non- contrast MRI during screening and at 12 months. * Willing to comply with regular follow up during the 12 month follow-up period. * Not a current candidate for partial or total knee arthroplasty. * WOMAC Score \>=6 in at least 2 categories.
Exclusion criteria
* BMI \>35 kg/m2 * Advanced peripheral arterial disease (resting ABI \<= 0.9). * Known significant peripheral arterial disease precluding common femoral catheterization * Have smoked tobacco regularly (smoking 1 or more tobacco product(s) per week) within the last year * Diabetics with hemoglobin A1C of \>9% * Previous lower extremity embolization * Uncontrolled emotional disorders per patient medical history * Chronic pain syndrome or currently under a pain contract. * Anatomic variants involving the lower extremities which would increase the risk of non-target embolization * Renal insufficiency based on an estimated GFR\<45 ml/min who are not already on hemodialysis. * Abnormal INR (\>1.5) * Platelet count \<50x109/L. * Currently receiving medications for anticoagulation which cannot safely be held for the procedure and for 7 days post-procedure. * Known severe allergy to iodine which cannot be adequately pre-medicated * Pregnant or intend to become pregnant within 6 months of the procedure * Contraindication to drugs used for moderate sedation during interventional procedures, including Midazolam and Fentanyl * Life expectancy \<60 months * Currently enrolled or who plan to enroll in other investigations that conflict with follow-up testing or confounds data in this trial * Contraindications to medical and physical rehabilitative treatments of OA. * Advanced atherosclerosis. * Current or previous lower extremity fistula. * Rheumatoid arthritis or seronegative arthropathies. * WOMAC Pain Scale \< 6 * Steroid injection in the affected joint within 3 months of screening. I- n investigator assessment, patient is not a candidate for study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as Assessed by Grade 3-4 Adverse events | 12 months | Safety will be reported using the combined number of grade 3 and 4 adverse events that occur in each arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) | baseline, 1 month, 6 months, 12 months | The KOOS measures 5 patient-relevant dimensions, each scored separately: Pain (nine items); Symptoms (seven items); ADL Function (17 items); Sport and Recreation Function (five items); Quality of Life (four items). Items are rated on a 5-point Likert scale from 0 (No problems) to 4 (Extreme problems). Dimension scores are calculated as the mean score of the included items divided by 4 and multiplied by 100. Range of subscale scores is 0-100 with higher scores indicating better function. |
| Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) | baseline, 1 month, 6 months, 12 months | The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a self-administered questionnaire consisting of 24 items divided into 3 subscales: Pain (5 items), stiffness (2 items), and physical function (17 items). Items are rated on a Likert scale of 0 (extreme) to 4 (none). Raw sub-scale scores are normalized to produce percentage scores in accordance with the KOOS by multiplying each score by 100/96. Total scores are a sum of the normalized sub-scales scores and range 0-100, with higher scores indicating better functioning. |
| IL-6 Concentration | baseline, 1 month, 12 months | Interleukin-6 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml. |
| Prostaglandin E2 Concentration | baseline, 1 month, 12 months | Prostaglandin E2 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml. |
| Matrix Metalloprotinase 1 Concentration | baseline, 1 month, 12 months | Matrix Metalloprotinase 1 concentrations will be measured in the serum and joint aspirate and reported in units of ng/ml. |
| Vascular Endothelial Growth Factor Concentration | baseline, 1 month, 12 months | Vascular Endothelial Growth Factor concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml. |
| C-Reactive Protein Concentration | baseline, 1 month, 12 months | C-Reactive Protein concentrations will be measured in the serum and reported in units of mg/L. |
| Erythrocyte Sedimentation Rate | baseline, 1 month, 12 months | Erythrocyte sedimentation rate will be performed using serum and reported in units of mm/hr. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORReza Talaie, MD
University of Minnesota
Outcome results
None listed