- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04682652
Genicular Artery Embolization Vs Observation for Symptomatic Knee Osteoarthritis (GRAVITY)
GRAVITY: Genicular Artery Embolization Versus Observation for the Treatment of Symptomatic Knee Osteoarthritis: a Randomized Controlled Trial
The purpose of this clinical trial is to determine whether genicular artery embolization (GAE) is an effective way to treat knee pain from osteoarthritis. Pain from arthritis is often due to underlying inflammation in the joint. The inflammation is associated with increased abnormal blood flow going to the specific area of pain. If the investigator can reduce the blood flow, the inflammation can be reduced and the pain can be controlled.
The GAE procedure is an experimental procedure to decrease the blood flow (embolize) to the specific region of the knee that is causing the pain. This will be done by infusing microscopic spheres into the specific blood vessel (genicular artery) supplying the area of pain in the knee. This is done through a procedure which is called an angiogram, which is done entirely through a pinhole at the creased of the thigh, using twilight (conscious) sedation.
The investigators have already completed an initial trial at UCLA, and shown that this procedure is safe and effective. The purpose of this new trial is to compare outcomes of people undergoing the GAE procedure to those who do not undergo the procedure. A total of 100 patients will be enrolled, and 2/3 of the patients will be randomly selected to undergo the GAE procedure. 1/3 will not undergo the procedure. This is known as a randomized trial. During the trial, all subjects will also get MRIs and fluid withdrawn from their knee joints at various timepoints in order to precisely figure out how the procedure works on a closer (microscopic) level.
Study Overview
Status
Intervention / Treatment
Detailed Description
This is a single-center, prospective, open-label randomized trial to compare outcomes of GAE versus observation, and to identify biomarkers and imaging endpoints that change in response to GAE.
Subjects will be considered enrolled in the study once they have provided informed consent and have been determined to meet all eligibility criteria. A total of 100 subjects will be enrolled in the double-arm study and will be followed for 24 months.
The study will involve a screening period in which patient eligibility is determined. Once eligibility is confirmed, subjects will then be randomized to GAE or observation in a 2:1 ratio. Group sample sizes of 67 and 33 achieve approximately 85% power to reject the null hypothesis of no difference in the clinical response defined by 50% or greater reduction in WOMAC between the treatment and observation arms with a significance level (alpha) of 0.050 using a two-sided two-proportions using Fisher's exact test. With 100 symptomatic knee osteoarthritis subjects, the power of study is approximately 85% where we assume a target response rate of 67.5% for the experimental arm and 31% for the observational arm with up to 20% drop-out rate prior to 6 months. All study subjects will undergo the initial procedures, consisting of a history and physical exam, dynamic contrast-enhanced knee MRI, blood serum and joint aspiration with biochemical analysis.
For the treatment arm, subjects will undergo GAE with Embozene microspheres (100 micron) (Varian Medical Systems). Observation group will not receive the GAE procedure at baseline, and will be counseled on conservative management with a referral or prescription for physical therapy. Follow-up visits will be at 1 month (± 2 weeks), 3 months (± 2 weeks), 6 months (± 2 weeks), 12 months (± 2 weeks), and 24 months (± 2 weeks) post-procedure. At these visits, subjects will complete the WOMAC, KOOS5, visual analog scale (VAS) pain score, undergo a directed physical examination, and report any new adverse events (AEs). At 6 and 24 months of follow-up, all subjects will also undergo dynamic contrast-enhanced knee MRI, and serum and joint aspiration with biochemical analysis.
At 6 months, subjects in the observation group will have the option to crossover to the GAE treatment arm. Subjects in the crossover group will then undergo GAE, with follow up at 1 month (± 2 weeks), 3 months (± 2 weeks), 6 months (± 2 weeks), 12 months (± 2 weeks), and 24 months (± 2 weeks) post-GAE. For the purposes of data analyses, the follow-up evaluations for crossover subjects will match those of the initial GAE subjects. For example, if a subject in the observation arm undergoes GAE crossover at 6 months, that will be considered the treatment visit, and then subject will undergo evaluation at 1, 3, 6, 12, and 24 months after GAE.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Saima Chaabane, PhD
- Phone Number: 424-465-4482
- Email: schaabane@mednet.ucla.edu
Study Contact Backup
- Name: Aniket Joglekar, BA
- Phone Number: 310-948-8026
- Email: ajoglekar@mednet.ucla.edu
Study Locations
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California
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Santa Monica, California, United States, 90404
- Recruiting
- UCLA Santa Monica Hospital
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Contact:
- Siddharth A Padia, MD
- Phone Number: 310-481-7545
- Email: spadia@mednet.ucla.edu
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria
Subjects must meet all of the following inclusion criteria in order to be eligible for this study:
- Provided informed consent
- Age ≥ 40 years and less than 80 years
- Ineligibility for or refusal of surgical management
- Moderate-severe knee pain as determined by visual analog scale > 5 out of 10
- Osteoarthritis based on X-ray. Kellgren-Lawrence score > 2 based on radiograph completed within 3 months of procedure date.
- Resistant/failed conservative treatment (e.g. NSAIDS/physical therapy/steroid joint injection/ hyaluronic acid joint injection) for at least 3 months
- Able to comply with all treatments and protocol follow-up visits
Exclusion Criteria
Subjects that meet any of the following exclusion criteria will not be eligible for this study:
- Mild knee pain as determined by visual analog scale < 5 out of 10
- OA on knee radiograph resulting in greater than 20 degree varus or valgus angulation
- Moderate loss of kidney function, define as estimated glomerular filtration rate of less than 45 mL/min.
- Significant arterial atherosclerosis that would limit selective angiography
- History of fibromyalgia, autoimmune, or inflammatory disorder
- History of any lumbar spine surgery, spine injections, or radicular pain in the extremity believed to originate from the spine
- Allergy to iodinated contrast agents
- Active Infection or malignancy
- Recent (within 12 months) or active cigarette use
- Prior total or partial knee replacement in the subject knee
- Active pregnancy
- Uncorrectable bleeding diasthesis
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: GAE Treatment
Subjects will be treated with a genicular artery embolization (GAE) procedure performed with Embozene Microspheres.
The microspheres will be delivered in a saline-contrast medium solution and will be delivered to the arteries supplying the areas of the subject's pain.
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Embozene is a medical device made by Boston Scientific approved in the United States for the treatment of hypervascular tumors and arteriovenous malformations.
It consists of thousands of microscopic spheres that are injected into the artery in the knee going to the region of pain.
One of the causes of pain in the setting of knee arthritis is increased blood flow going to the specific area of pain.
The goal of this procedure is to decrease the blood flow (embolize) to the specific region of the knee that is causing your pain.
This is done by infusing Embozene particles into the specific blood vessel (genicular artery) supplying the area of pain in the knee.
Other Names:
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No Intervention: Observational
Subjects randomized to the observational group will not undergo the experimental GAE Treatment. PI will offer subjects enrolled into the observational group to crossover to the experimental GAE Treatment group after they have completed their 6-month follow-up assessments. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in clinical response
Time Frame: 6 months
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The primary evaluation is the change in clinical response, measured by The Western Ontario and McMaster Universities Arthritis Index (WOMAC).
The primary endpoint is percentage of subjects achieving at least a 50% reduction in WOMAC at 6 months with an intent-to-treat analysis.
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6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Short term clinical outcomes
Time Frame: 1 and 3 months
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• Compare clinical success rates (defined as at least 50% reduction in WOMAC) between GAE and observation at 1 and 3 months.
This will be a intent-to-treat analysis.
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1 and 3 months
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Clinic outcomes at multiple timepoints
Time Frame: 1-24 months
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• Compare clinical success rates (defined as at least 50% reduction in WOMAC) between GAE and observation at various timepoints: 1 months, 3 months, 6 months, 12 months, 24 months.
This will be a per-protocol analysis.
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1-24 months
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Degree of change in clinical outcomes via WOMAC
Time Frame: 1-24 months
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• Compare median decrease in WOMAC (measured by percentage) between GAE and observation at various timepoints: 1 month, 3 months, 6 months, 12 months, 24 months.
This will be a per-protocol analysis.
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1-24 months
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Decrease in pain
Time Frame: 1-24 months
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• Compare median decrease in pain (measured by VAS: visual analog scale) between GAE and observation at various timepoints: 1 month, 3 months, 6 months, 12 months, 24 months.
This will be a per-protocol analysis.
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1-24 months
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Change in quality of life
Time Frame: 1-24 months
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• Compare median improvement in health-related quality of life (measured by KOOS5) between GAE and observation at various timepoints: 1 month, 3 months, 6 months, 12 months, 24 months.
This will be a per-protocol analysis.
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1-24 months
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Change in MRI
Time Frame: 6-24 months
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• To assess changes in imaging (MRI) in patients undergoing GAE versus observation, at 0, 6, and 24 months.
This will be a per-protocol exploratory analysis.
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6-24 months
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Change in inflammatory biomarkers
Time Frame: 6-24 months
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• To assess changes in inflammatory markers in patients undergoing GAE versus observation at 0, 6 and 24 months.
This will be a per-protocol exploratory analysis.
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6-24 months
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Correlation of baseline characteristics with clinical response
Time Frame: 1-24 months
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• To assess how differences in baseline clinical, imaging, and biochemical characteristics correlate with clinical response.
This will be a per-protocol exploratory analysis.
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1-24 months
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Degree of progression of osteoarthritis
Time Frame: 24 months
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• To assess the degree of progression of osteoarthritis via changes in knee radiograph at 0 and 24 months in patients undergoing GAE versus observation.
This will be a per-protocol exploratory analysis.
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24 months
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Safety assessment
Time Frame: 24 months
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Assess safety via tabulation of adverse events
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24 months
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Pain medication use
Time Frame: 24 months
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To assess change in pain medication use after GAE versus observation.
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24 months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Siddharth A Padia, MD, University of California, Los Angeles
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 22-001004
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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