Geniculate Artery Embolization for Osteoarthritis

Osteoarthritis Clinical Trial

Official title:

Geniculate Artery Embolization for Osteoarthritis: Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04456569
• Other study ID #: RAD-2019-27368
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2022
• Est. completion date: February 1, 2026

Study information

• Verified date: March 2024
• Source: University of Minnesota
• Contact: Connie Dale, MD
• Email: dalex179[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: February 1, 2026
• Est. primary completion date: February 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Osteo Arthritis Knee
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

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.

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Feasibility as Assessed by Protocol Adherence	Feasibility will be assessed and reported as the number of participants in each arm who drop out due to a lack of protocol adherence.	12 months
Other	Feasibility as Assessed by Recruitment Rate	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).	12 months
Primary	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.	12 months
Secondary	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.	baseline, 1 month, 6 months, 12 months
Secondary	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.	baseline, 1 month, 6 months, 12 months
Secondary	IL-6 Concentration	Interleukin-6 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.	baseline, 1 month, 12 months
Secondary	Prostaglandin E2 Concentration	Prostaglandin E2 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.	baseline, 1 month, 12 months
Secondary	Matrix Metalloprotinase 1 Concentration	Matrix Metalloprotinase 1 concentrations will be measured in the serum and joint aspirate and reported in units of ng/ml.	baseline, 1 month, 12 months
Secondary	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.	baseline, 1 month, 12 months
Secondary	C-Reactive Protein Concentration	C-Reactive Protein concentrations will be measured in the serum and reported in units of mg/L.	baseline, 1 month, 12 months
Secondary	Erythrocyte Sedimentation Rate	Erythrocyte sedimentation rate will be performed using serum and reported in units of mm/hr.	baseline, 1 month, 12 months