Geniculate Artery Embolization for Osteoarthritis

• ClinicalTrials.gov Identifier: NCT04456569
• Recruitment Status: Recruiting
• First Posted: July 2, 2020
• Last Update Posted: September 10, 2022
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

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.

Condition or disease	Intervention/treatment	Phase
Osteo Arthritis Knee; Arthritis; Osteoarthritis; Osteoarthritis, Knee	Device: Geniculate Artery Embolization	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Geniculate Artery Embolization for Osteoarthritis: Pilot Study
• Actual Study Start Date: February 1, 2022
• Estimated Primary Completion Date: February 2024
• Estimated Study Completion Date: February 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: GAE + Standard of Care; Participants in this arm will receive geniculate artery embolization and standard of care.	Device: Geniculate Artery Embolization; 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.
No Intervention: Standard of Care; Participants in this arm will receive standard of care only.

Outcome Measures

Primary Outcome Measures :

1. Safety as Assessed by Grade 3-4 Adverse events [ Time Frame: 12 months ]
   Safety will be reported using the combined number of grade 3 and 4 adverse events that occur in each arm.

Secondary Outcome Measures :

1. Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) [ Time Frame: 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.

2. Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [ Time Frame: 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.
3. IL-6 Concentration [ Time Frame: baseline, 1 month, 12 months ]
   Interleukin-6 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.
4. Prostaglandin E2 Concentration [ Time Frame: baseline, 1 month, 12 months ]
   Prostaglandin E2 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.
5. Matrix Metalloprotinase 1 Concentration [ Time Frame: 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.
6. Vascular Endothelial Growth Factor Concentration [ Time Frame: 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.
7. C-Reactive Protein Concentration [ Time Frame: baseline, 1 month, 12 months ]
   C-Reactive Protein concentrations will be measured in the serum and reported in units of mg/L.
8. Erythrocyte Sedimentation Rate [ Time Frame: baseline, 1 month, 12 months ]
   Erythrocyte sedimentation rate will be performed using serum and reported in units of mm/hr.

Other Outcome Measures:

1. Feasibility as Assessed by Protocol Adherence [ Time Frame: 12 months ]
   Feasibility will be assessed and reported as the number of participants in each arm who drop out due to a lack of protocol adherence.
2. Feasibility as Assessed by Recruitment Rate [ Time Frame: 12 months ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Pooya Torkian, MD; 6126246904; ptorkian@umn.edu

Locations

United States, Minnesota

University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: Reza Talaie, MD

Sponsors and Collaborators

University of Minnesota

Investigators

• Principal Investigator: Reza Talaie, MD; University of Minnesota

More Information

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT04456569
• Other Study ID Numbers: RAD-2019-27368
• First Posted: July 2, 2020
• Last Update Posted: September 10, 2022
• Last Verified: September 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by University of Minnesota:

Embolotherapy

Additional relevant MeSH terms:

Arthritis; Osteoarthritis; Osteoarthritis, Knee; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases