Geniculate Artery Embolization for Osteoarthritis
Primary Purpose
Osteo Arthritis Knee, Arthritis, Osteoarthritis
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Geniculate Artery Embolization
Sponsored by
About this trial
This is an interventional treatment trial for Osteo Arthritis Knee focused on measuring Embolotherapy
Eligibility Criteria
Inclusion Criteria:
- Unilaterally dominant symptomatic osteoarthritis (bilateral radiographic OA will not exclude)
- Patients who are 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 0-1 intra-articular injections of the affected knee)
- Kellgren-Lawrence grade 1, 2, or 3 on radiograph of the knee
- Patients who are willing to comply with the protocol requirements and willing to undergo non-contrast MRI 1-30 days prior to procedure and at 12 months following procedure
- Patients who are willing to comply with regular follow up during the 12 month follow-up period
- Patients who have been evaluated by an orthopaedic surgeon or sports medicine provider and deemed to not be a current candidate for partial or total knee arthroplasty. These patients do, however, need to be considered a potential candidate for partial or total knee as an end point following the natural history of osteoarthritis.
- Patients with WOMAC Score >=6 in at least 2 categories
Exclusion Criteria:
- Patients with a weight >250 pounds
- Patients with advanced peripheral arterial disease (resting ABI <= 0.9)
- Patients with known significant peripheral arterial disease precluding common femoral catheterization
- Patients who do smoke or have smoked tobacco regularly (smoking 1 or more tobacco product(s) per week) within the last year
- Patients with diabetes who have a hemoglobin A1C of >9%
- Patients who have undergone previous lower extremity embolization
- Patients with uncontrolled emotional disorders per patient medical history
- Patients with chronic pain syndrome or currently under a pain contract
- Patients with anatomic variants involving the lower extremities which would increase the risk of non-target embolization
- Patients with renal insufficiency based on an estimated GFR<45 ml/min who are not already on hemodialysis.
- Patients with an abnormal INR (>1.5).
- Patients with a platelet count <50x109/L.
- Patients who are currently receiving medications for anticoagulation which cannot safely be held for the procedure and for 7 days post-procedure.
- Patients with a known severe allergy to iodine which cannot be adequately pre-medicated
- Patients who are pregnant or intend to become pregnant within 6 months of the procedure
- Patients with a contraindication to drugs used for moderate sedation during interventional procedures, including Midazolam and Fentanyl
- Patients with a life expectancy <60 months
- Patients who are currently enrolled or who plan to enroll in other investigations that conflict with follow-up testing or confounds data in this trial
- Patients with contraindications to medical and physical rehabilitative treatments of OA
- Patients with known advanced atherosclerosis
- Patients with known current or previous lower extremity fistula
- Patients with rheumatoid arthritis or seronegative arthropathies
- Patients with prior ipsilateral knee surgery.
- Patients with WOMAC Pain Scale < 6
- Patients having received more than one steroid injection in the affected joint or an injection in the affected joint within 3 months of screening
Sites / Locations
- University of MinnesotaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
GAE + Standard of Care
Standard of Care
Arm Description
Participants in this arm will receive geniculate artery embolization and standard of care.
Participants in this arm will receive standard of care only.
Outcomes
Primary Outcome Measures
Safety as Assessed by Grade 3-4 Adverse events
Safety will be reported using the combined number of grade 3 and 4 adverse events that occur in each arm.
Secondary Outcome Measures
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS)
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)
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
Interleukin-6 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.
Prostaglandin E2 Concentration
Prostaglandin E2 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.
Matrix Metalloprotinase 1 Concentration
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
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
C-Reactive Protein concentrations will be measured in the serum and reported in units of mg/L.
Erythrocyte Sedimentation Rate
Erythrocyte sedimentation rate will be performed using serum and reported in units of mm/hr.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04456569
Brief Title
Geniculate Artery Embolization for Osteoarthritis
Official Title
Geniculate Artery Embolization for Osteoarthritis: Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2022 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
February 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteo Arthritis Knee, Arthritis, Osteoarthritis, Osteoarthritis, Knee
Keywords
Embolotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
GAE + Standard of Care
Arm Type
Experimental
Arm Description
Participants in this arm will receive geniculate artery embolization and standard of care.
Arm Title
Standard of Care
Arm Type
No Intervention
Arm Description
Participants in this arm will receive standard of care only.
Intervention Type
Device
Intervention Name(s)
Geniculate Artery Embolization
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety as Assessed by Grade 3-4 Adverse events
Description
Safety will be reported using the combined number of grade 3 and 4 adverse events that occur in each arm.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS)
Description
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.
Time Frame
baseline, 1 month, 6 months, 12 months
Title
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
Description
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.
Time Frame
baseline, 1 month, 6 months, 12 months
Title
IL-6 Concentration
Description
Interleukin-6 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.
Time Frame
baseline, 1 month, 12 months
Title
Prostaglandin E2 Concentration
Description
Prostaglandin E2 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.
Time Frame
baseline, 1 month, 12 months
Title
Matrix Metalloprotinase 1 Concentration
Description
Matrix Metalloprotinase 1 concentrations will be measured in the serum and joint aspirate and reported in units of ng/ml.
Time Frame
baseline, 1 month, 12 months
Title
Vascular Endothelial Growth Factor Concentration
Description
Vascular Endothelial Growth Factor concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.
Time Frame
baseline, 1 month, 12 months
Title
C-Reactive Protein Concentration
Description
C-Reactive Protein concentrations will be measured in the serum and reported in units of mg/L.
Time Frame
baseline, 1 month, 12 months
Title
Erythrocyte Sedimentation Rate
Description
Erythrocyte sedimentation rate will be performed using serum and reported in units of mm/hr.
Time Frame
baseline, 1 month, 12 months
Other Pre-specified Outcome Measures:
Title
Feasibility as Assessed by Protocol Adherence
Description
Feasibility will be assessed and reported as the number of participants in each arm who drop out due to a lack of protocol adherence.
Time Frame
12 months
Title
Feasibility as Assessed by Recruitment Rate
Description
Feasibility will be assessed and reported as the mean number of participants who are enrolled each month over the length of the study (12 months).
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Unilaterally dominant symptomatic osteoarthritis (bilateral radiographic OA will not exclude)
Patients who are 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 0-1 intra-articular injections of the affected knee)
Kellgren-Lawrence grade 1, 2, or 3 on radiograph of the knee
Patients who are willing to comply with the protocol requirements and willing to undergo non-contrast MRI 1-30 days prior to procedure and at 12 months following procedure
Patients who are willing to comply with regular follow up during the 12 month follow-up period
Patients who have been evaluated by an orthopaedic surgeon or sports medicine provider and deemed to not be a current candidate for partial or total knee arthroplasty. These patients do, however, need to be considered a potential candidate for partial or total knee as an end point following the natural history of osteoarthritis.
Patients with WOMAC Score >=6 in at least 2 categories
Exclusion Criteria:
Patients with a weight >250 pounds
Patients with advanced peripheral arterial disease (resting ABI <= 0.9)
Patients with known significant peripheral arterial disease precluding common femoral catheterization
Patients who do smoke or have smoked tobacco regularly (smoking 1 or more tobacco product(s) per week) within the last year
Patients with diabetes who have a hemoglobin A1C of >9%
Patients who have undergone previous lower extremity embolization
Patients with uncontrolled emotional disorders per patient medical history
Patients with chronic pain syndrome or currently under a pain contract
Patients with anatomic variants involving the lower extremities which would increase the risk of non-target embolization
Patients with renal insufficiency based on an estimated GFR<45 ml/min who are not already on hemodialysis.
Patients with an abnormal INR (>1.5).
Patients with a platelet count <50x109/L.
Patients who are currently receiving medications for anticoagulation which cannot safely be held for the procedure and for 7 days post-procedure.
Patients with a known severe allergy to iodine which cannot be adequately pre-medicated
Patients who are pregnant or intend to become pregnant within 6 months of the procedure
Patients with a contraindication to drugs used for moderate sedation during interventional procedures, including Midazolam and Fentanyl
Patients with a life expectancy <60 months
Patients who are currently enrolled or who plan to enroll in other investigations that conflict with follow-up testing or confounds data in this trial
Patients with contraindications to medical and physical rehabilitative treatments of OA
Patients with known advanced atherosclerosis
Patients with known current or previous lower extremity fistula
Patients with rheumatoid arthritis or seronegative arthropathies
Patients with prior ipsilateral knee surgery.
Patients with WOMAC Pain Scale < 6
Patients having received more than one steroid injection in the affected joint or an injection in the affected joint within 3 months of screening
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Connie Dale, MD
Email
dalex179@umn.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Allison Wolf, MPH
Email
wolfx494@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reza Talaie, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Reza Talaie, MD
12. IPD Sharing Statement
Learn more about this trial
Geniculate Artery Embolization for Osteoarthritis
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