Osteo Arthritis Knee
Conditions
Keywords
embolization, vascular
Brief summary
Purpose: To evaluate embolization as a treatment for OA related knee pain versus placebo to demonstrate the actual effect of embolization on pain and disability. Participants: There will be 21 subjects enrolled over the age 40 with knee pain secondary to arthritis. Procedures (methods): This will be a single-blinded randomized-controlled study of GAE versus placebo in a small population with knee pain secondary to arthritis to determine safety and efficacy. Clinical procedures and evaluations will consist of a preoperative screening assessment to determine if the potential study subject meets the inclusion and exclusion criteria, enrollment, surgical procedure for geniculate artery embolization, and follow-up visits at 24 hours, 2 weeks, 1, 3, 6, & 12 months. An MRI may be performed after the 1-month visit.
Detailed description
This will be a single-blinded randomized-controlled study of GAE versus placebo in a small population with knee pain secondary to arthritis to determine safety and efficacy. After Institutional Review Board (IRB) approval of a written informed consent and over, approximately a 24 month duration, N=21 subjects will be recruited. Only subjects ≥ 40 years will be screened for study recruitment. Subjects will be randomized in a 2:1 ratio of GAE:Placebo and will be blinded from study treatment (see flow chart below). The placebo procedure will be a diagnostic angiogram of the knee, without embolization. Appropriate measures will be taken to ensure patients and nursing staff caring for the patient are blinded to assignment. Each patient will be told at the time of recruitment that they may be randomly assigned to sham, but if after 1 month they have not had symptom improvement, their assigned procedure would be revealed and, if they had undergone a sham procedure, they will be allowed to proceed with embolization. This second procedure should be shorter than a complete angiogram and embolization, as the detailed angiogram will not need to be repeated, and therefore both arms will have similar total radiation dose. Clinical procedures and evaluations will consist of a preoperative screening assessment to determine if the potential study subject meets the inclusion and exclusion criteria, enrollment, surgical procedure for geniculate artery embolization, and follow-up visits at 24 hours, 2 weeks, 1, 3, 6, & 12 months. An MRI may be performed after the 1-month visit.
Interventions
Gel-Bead Microspheres will be used for geniculate artery embolization (GAE) in subjects with knee osteoarthritis.
DIAGNOSTIC_TESTSham Procedure
Patients will receive a sham procedure, which will include a diagnostic angiogram
Sponsors
Medtronic
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
This will be a single-blinded randomized-controlled study of GAE versus placebo in a small population with knee pain secondary to arthritis to determine safety and efficacy. The placebo procedure will be a diagnostic angiogram of the knee, without embolization. Appropriate measures will be taken to ensure patients and nursing staff caring for the patient are blinded to assignment. Each patient will be told at the time of recruitment that they may be randomly assigned to sham, but if after 1 month they have not had symptom improvement, their assigned procedure would be revealed and, if they had undergone a sham procedure, they will be allowed to proceed with embolization.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Moderate to severe knee pain (visual analog scale (VAS) \> 50 mm), and Pain refractory to at least 3 months\* of conservative therapies (anti- inflammatory drugs, or physical therapy, or muscle strengthening, or intra- articular injections), and Kellgren-Lawrence grade 1, 2 or 3 on radiograph of the knee.
Exclusion criteria
Current local infection, or Life expectancy less than 6 months, or Known advanced atherosclerosis, or Rheumatoid or infectious arthritis, or Prior knee surgery, or Uncorrectable coagulopathy including international normalized ratio (INR) \> 2.5 or platelets \< 30,000, or Iodine allergy resulting in anaphylaxis, or Renal dysfunction as defined by serum creatinine \>1.6 dl/mg or estimated glomerular filtration rate (eGFR) \<60 obtained within the past 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Patient Pain as Measured by VAS at Month 3 | 3 months following procedure | The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain will be assessed at each of the patient's follow-up visits and used to measure the change from baseline (prior to the GAE procedure). The investigators will use this to measure if the patient's pain level decreases. |
| Mean Patient Pain as Measured by VAS at Month 1 | 1 month following procedure | The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain will be assessed at each of the patient's follow-up visits and used to measure the change from baseline (prior to the GAE procedure). The investigators will use this to measure if the patient's pain level decreases. |
| Mean WOMAC Scores at Month 3 | 3 months following procedure | Western Ontario and McMaster University Osteoarthritis Index (WOMAC) will be used to measure function. This is a score derived from a questionnaire in which the patient answers questions regarding rheumatic symptoms in the subcategories of pain (5 items), stiffness (2 items), and physical function (17 items). Individuals select the level of difficulty they have performing various tasks using a 5 point Likert scale (0=None, 1=Slightly, 3=Very, 4=Extremely). Then, results are scored with a total score (minimum 0; maximum 96). A higher score indicates more difficulty in each of the categories. |
| Mean WOMAC Scores at Month 6 | 6 months following procedure | Western Ontario and McMaster University Osteoarthritis Index (WOMAC) will be used to measure function. This is a score derived from a questionnaire in which the patient answers questions regarding rheumatic symptoms in the subcategories of pain (5 items), stiffness (2 items), and physical function (17 items). Individuals select the level of difficulty they have performing various tasks using a 5 point Likert scale (0=None, 1=Slightly, 3=Very, 4=Extremely). Then, results are scored with a total score (minimum 0; maximum 96). A higher score indicates more difficulty in each of the categories. |
| Mean Patient Pain as Measured by VAS at Month 6 | 6 months following procedure | The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain will be assessed at each of the patient's follow-up visits and used to measure the change from baseline (prior to the GAE procedure). The investigators will use this to measure if the patient's pain level decreases. |
| Mean WOMAC Scores at Month 1 | 1 month following procedure | Western Ontario and McMaster University Osteoarthritis Index (WOMAC) will be used to measure function. This is a score derived from a questionnaire in which the patient answers questions regarding rheumatic symptoms in the subcategories of pain (5 items), stiffness (2 items), and physical function (17 items). Individuals select the level of difficulty they have performing various tasks using a 5 point Likert scale (0=None, 1=Slightly, 3=Very, 4=Extremely). Then, results are scored with a total score (minimum 0; maximum 96). A higher score indicates more difficulty in each of the categories. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Reduction in Medication | 12 months following procedure | Reduction in the number or strength of previously initiated OA medical therapy (e.g. NSAIDs) at 6 months follow-up, which will be summarized using counts. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Patient With Complications | 6 months following procedure for the GAE Procedure and Crossover Arm Arms/Groups and 1 month following procedure for the Sham Procedure Arm/Group | The number and description of complications, adverse events, or poor outcomes (such as no improvement in pain) that are secondary to the GAE procedure, which will be summarized using counts. |
Countries
United States
Participant flow
Pre-assignment details
All patients that received the sham procedure crossed over into the crossover arm.
Participants by arm
| Arm | Count |
|---|---|
| GAE Procedure Patients will be randomized to receive the Geniculate Artery Embolization Procedure
Geniculate Artery Embolization: Gel-Bead Microspheres will be used for geniculate artery embolization (GAE) in subjects with knee osteoarthritis. | 14 |
| Sham Procedure First, Then GAE Procedure Patients will be randomized to a sham procedure.
Sham Procedure: Patients will receive a sham procedure, which will include a diagnostic angiogram
If after 1 month patients see no improvement, they will be unblinded and crossover to receive the Geniculate Artery Embolization Procedure
Geniculate Artery Embolization: Gel-Bead Microspheres will be used for geniculate artery embolization (GAE) in subjects with knee osteoarthritis. | 7 |
| Total | 21 |
Baseline characteristics
| Characteristic | Total | GAE Procedure | Sham Procedure First, Then GAE Procedure |
|---|---|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 7.8 | 63.9 years STANDARD_DEVIATION 8.4 | 62.9 years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 11 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 11 Participants | 4 Participants |
| Region of Enrollment United States | 21 Participants | 14 Participants | 7 Participants |
| Sex: Female, Male Female | 18 Participants | 12 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 1 Participants |
| VAS Baseline | 14.3 mm STANDARD_DEVIATION 3.1 | 13.9 mm STANDARD_DEVIATION 3.1 | 15.4 mm STANDARD_DEVIATION 3.5 |
| VAS baseline following sham procedure | 14 mm STANDARD_DEVIATION 2.7 | — | 14 mm STANDARD_DEVIATION 2.7 |
| WOMAC Baseline Following Sham Procedure | 65.9 units on a scale STANDARD_DEVIATION 11.3 | — | 65.9 units on a scale STANDARD_DEVIATION 11.3 |
| WOMAC Baseline for study | 66.6 units on a scale STANDARD_DEVIATION 14.4 | 64.9 units on a scale STANDARD_DEVIATION 16.6 | 70.9 units on a scale STANDARD_DEVIATION 13.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 8 / 14 | 2 / 7 | 5 / 7 |
| serious Total, serious adverse events | 0 / 14 | 0 / 7 | 0 / 7 |
Outcome results
Primary
Mean Patient Pain as Measured by VAS at Month 1
The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain will be assessed at each of the patient's follow-up visits and used to measure the change from baseline (prior to the GAE procedure). The investigators will use this to measure if the patient's pain level decreases.
Time frame: 1 month following procedure
Population: One participant was excluded from the GAE arm due to increased pain that resulted in additional medication and was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GAE Procedure | Mean Patient Pain as Measured by VAS at Month 1 | 30.5 mm | Standard Deviation 27.9 |
| Sham Procedure | Mean Patient Pain as Measured by VAS at Month 1 | 78.4 mm | Standard Deviation 10.2 |
| Crossover Arm | Mean Patient Pain as Measured by VAS at Month 1 | 39.8 mm | Standard Deviation 31 |
Primary
Mean Patient Pain as Measured by VAS at Month 3
The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain will be assessed at each of the patient's follow-up visits and used to measure the change from baseline (prior to the GAE procedure). The investigators will use this to measure if the patient's pain level decreases.
Time frame: 3 months following procedure
Population: One participant was excluded from the GAE arm due to increased pain that resulted in additional medication and was excluded from the analysis. One additional participant in this arm did not have data available at the 3 month visit. All sham participants crossed over to receive treatment after 1 month, thus no 3-month data available for this group. One patient in the crossover arm did not have VAS data available for the 3 month visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GAE Procedure | Mean Patient Pain as Measured by VAS at Month 3 | 21.3 mm | Standard Deviation 27.9 |
| Crossover Arm | Mean Patient Pain as Measured by VAS at Month 3 | 41.2 mm | Standard Deviation 31.1 |
Primary
Mean Patient Pain as Measured by VAS at Month 6
The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain will be assessed at each of the patient's follow-up visits and used to measure the change from baseline (prior to the GAE procedure). The investigators will use this to measure if the patient's pain level decreases.
Time frame: 6 months following procedure
Population: One participant was excluded from the GAE arm due to increased pain that resulted in additional medication and was excluded from the analysis. All sham participants crossed over to receive treatment after 1 month, thus no 6-month data available for this group. One patient in the crossover arm did not have VAS data available for the 6 month visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GAE Procedure | Mean Patient Pain as Measured by VAS at Month 6 | 20.3 mm | Standard Deviation 25.6 |
| Crossover Arm | Mean Patient Pain as Measured by VAS at Month 6 | 19.2 mm | Standard Deviation 35.3 |
Primary
Mean WOMAC Scores at Month 1
Western Ontario and McMaster University Osteoarthritis Index (WOMAC) will be used to measure function. This is a score derived from a questionnaire in which the patient answers questions regarding rheumatic symptoms in the subcategories of pain (5 items), stiffness (2 items), and physical function (17 items). Individuals select the level of difficulty they have performing various tasks using a 5 point Likert scale (0=None, 1=Slightly, 3=Very, 4=Extremely). Then, results are scored with a total score (minimum 0; maximum 96). A higher score indicates more difficulty in each of the categories.
Time frame: 1 month following procedure
Population: One participant was excluded from the GAE arm due to increased pain that resulted in additional medication and was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GAE Procedure | Mean WOMAC Scores at Month 1 | 34.7 units on a scale | Standard Deviation 24 |
| Sham Procedure | Mean WOMAC Scores at Month 1 | 65.9 units on a scale | Standard Deviation 11.3 |
| Crossover Arm | Mean WOMAC Scores at Month 1 | 46.3 units on a scale | Standard Deviation 29.6 |
Primary
Mean WOMAC Scores at Month 3
Western Ontario and McMaster University Osteoarthritis Index (WOMAC) will be used to measure function. This is a score derived from a questionnaire in which the patient answers questions regarding rheumatic symptoms in the subcategories of pain (5 items), stiffness (2 items), and physical function (17 items). Individuals select the level of difficulty they have performing various tasks using a 5 point Likert scale (0=None, 1=Slightly, 3=Very, 4=Extremely). Then, results are scored with a total score (minimum 0; maximum 96). A higher score indicates more difficulty in each of the categories.
Time frame: 3 months following procedure
Population: One participant was excluded from the GAE arm due to increased pain that resulted in additional medication and was excluded from the analysis. One additional participant in this arm did not have data available at the 3 month visit. All sham participants crossed over to receive treatment after 1 month, thus no 3-month data available for this group. One patient in the crossover arm did not have WOMAC data available for the 3 month visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GAE Procedure | Mean WOMAC Scores at Month 3 | 19.7 units on a scale | Standard Deviation 20.5 |
| Crossover Arm | Mean WOMAC Scores at Month 3 | 39.5 units on a scale | Standard Deviation 27.3 |
Primary
Mean WOMAC Scores at Month 6
Western Ontario and McMaster University Osteoarthritis Index (WOMAC) will be used to measure function. This is a score derived from a questionnaire in which the patient answers questions regarding rheumatic symptoms in the subcategories of pain (5 items), stiffness (2 items), and physical function (17 items). Individuals select the level of difficulty they have performing various tasks using a 5 point Likert scale (0=None, 1=Slightly, 3=Very, 4=Extremely). Then, results are scored with a total score (minimum 0; maximum 96). A higher score indicates more difficulty in each of the categories.
Time frame: 6 months following procedure
Population: One participant was excluded from the GAE arm due to increased pain that resulted in additional medication and was excluded from the analysis. All sham participants crossed over to receive treatment after 1 month, thus no 6-month data available for this group. One crossover participant did not have WOMAC data available for the 6 month visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GAE Procedure | Mean WOMAC Scores at Month 6 | 29 units on a scale | Standard Deviation 25 |
| Crossover Arm | Mean WOMAC Scores at Month 6 | 26 units on a scale | Standard Deviation 31 |
Secondary
Number of Participants With Reduction in Medication
Reduction in the number or strength of previously initiated OA medical therapy (e.g. NSAIDs) at 6 months follow-up, which will be summarized using counts.
Time frame: 12 months following procedure
Population: All participants in the sham arm crossed over 1 month after the sham procedure, thus no 6-month data available for this group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GAE Procedure | Number of Participants With Reduction in Medication | 5 Participants |
| Sham Procedure | Number of Participants With Reduction in Medication | 0 Participants |
| Crossover Arm | Number of Participants With Reduction in Medication | 1 Participants |
Other Pre-specified
Number of Patient With Complications
The number and description of complications, adverse events, or poor outcomes (such as no improvement in pain) that are secondary to the GAE procedure, which will be summarized using counts.
Time frame: 6 months following procedure for the GAE Procedure and Crossover Arm Arms/Groups and 1 month following procedure for the Sham Procedure Arm/Group
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GAE Procedure | Number of Patient With Complications | 8 Participants |
| Sham Procedure | Number of Patient With Complications | 2 Participants |
| Crossover Arm | Number of Patient With Complications | 5 Participants |