Clinical trial NCT05700682: Perfusion MRI-targeted Joint Embolization for Chronic Musculoskeletal Pain of the Shoulder, Hip and Knee
Official title: Perfusion MRI-targeted Joint Embolization to Diagnose and Treat Neovascularity Associated with Chronic Musculoskeletal Pain of the Shoulder, Hip and Knee: a Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Osteoarthritis, Knee
Osteoarthritis, Hip
Osteo Arthritis Shoulders
Synovitis of Knee
Synovitis/Tenosynovitis - Hip
Synovitis
Pain, Chronic
Keywords: joint
embolization
neovascularity
pain
knee
hip
shoulder
Lead sponsor: Palo Alto Veterans Institute for Research
Sponsor class: OTHER
Collaborators: name: Varian Medical Systems
First posted: 2023-01-26
Enrollment: 120
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be veterans eligible for care at the VA. Anticipated age range is 25-80. Gender will be predominantly male (approximately 90%), concordant with demographic information of the VA population. Pregnant women, children, vulnerable subjects, study personnel and students will not be eligible for enrollment.

Brief summary: In this work the investigators will study the relationship between chronic musculoskeletal pain and abnormal blood flow (neovascularity) around the shoulder, hip and knee. Veterans with as history of chronic shoulder, hip or knee pain and mild/moderate joint degenerative changes will be potential study subjects. Blood flow around joints will be evaluated using perfusion magnetic resonance imaging (MRI). Participants with demonstrably abnormal blood flow around their painful joint will be eligible for enrollment in a pilot study of joint embolization to treat their pain. Participants who choose to not undergo treatment will be re-assessed with MRI after one year to characterize the natural history of joint neovascularity and its relationship to pain.

Detailed description: 1. Joint MRI (shoulder, hip, knee) is ordered by a clinical provider due to ongoing/chronic joint pain. At the time of MR exam protocoling, investigators review prior imaging and determine that the patient has mild-moderate osteoarthritis. Patient is identified as a potential participant and is sent a letter by physical mail or e-mail (signed by PIs) discussing the research project. Subsequently, the clinical research coordinator reaches out to the potential participant by phone 7-14 days before the date of the MR exam to assess interest in the study.
2. Participant is interested and enrolls in the Diagnostic Arm of the study. Upon enrollment, the participant will undergo perfusion MRI and cartilage parameter mapping at the time of the initial MR exam (a 15-minute "add on" scan with Multihance intravenous contrast at the end of the standard clinical MRI). The participant will also complete a WOMAC (knee/hip) or WORC (shoulder) survey to document the baseline characteristics of their pain.
3. If there is NO neovascularity on the perfusion MRI, the participant will remain in the Diagnostic Arm of the study. Participants who remain in the Diagnostic Arm will undergo follow-up WOMAC surveys at 6 months / 1 year; and a research perfusion MR at one year. Follow-up data from the 1-year visit will represent the primary clinical and imaging endpoints of the Diagnostic Arm.
4. If neovascularity is present, the participant will be offered enrollment into the Therapeutic Arm. Participants not interested in the Therapeutic Arm will remain in the Diagnostic Arm.
5. Participants who elect to enroll in the Therapeutic Arm of the study are referred to the study investigators, who will screen for exclusion criteria. Importantly, if the participant has risk factors for or confirmed peripheral arterial disease (PAD), they must undergo CT angiography of the relevant anatomy (abdomen/pelvis with or without lower extremity runoff). If the participant does not meet any exclusion criteria, they will be scheduled for embolization therapy of their painful joint (shoulder, hip or knee). The participant will undergo embolization under fluoroscopic guidance using Embozene microspheres. Briefly, the relevant arterial vessels supplying the joint of interest will be accessed with an arterial catheter. The presence of abnormal peri-articular vessels seen on MRI will be confirmed during fluoroscopic imaging with injection of contrast material (Omnipaque). These abnormal vessels will then be embolized via careful injection of bland embolic particles (Embozene microspheres). After embolization, participant will attend one clinic follow-up visit at 2 weeks to screen for side effects or complications. The participant will be surveyed for their symptoms (WOMAC/WORC) at 1, 3, 6 and 12-months post-treatment. They will undergo research MR exams perfusion and cartilage parameter mapping at 3- and 12-months post-treatment.
6. Recruitment will occur over 1.5 years. Follow-up in both Arms will occur over 1 year. After completion of the study, the investigators anticipate approximately 3-4 months will be required for data analysis and manuscript preparation. Total study duration will therefore be 2.5 to 3 years.

Eligibility criteria: Inclusion Criteria (Both Arms):

1. Participants must be Veterans who receive care in the VA system.
2. Participants must have a history of chronic pain of the shoulder, hip or knee for at least 1 year.
3. Participants must have mild to moderate degenerative changes of the painful joint as depicted on prior imaging (X-ray, CT or MRI).
4. Participants must have undergone at least one failed primary treatment for their chronic pain (e.g. physical therapy, NSAIDs, steroid injection).
5. Participants must have an MRI of their painful joint (shoulder, hip or knee) ordered by a clinical provider.

Inclusion Criteria (Therapeutic Arm):

1. Participants must have enrolled in the Diagnostic Arm of the study and must have undergone perfusion MR imaging of their painful joint.
2. Participants must have evidence of peri-articular hypervascularity on their perfusion MR exams. This will be determined by the study PIs.

Exclusion Criteria (Diagnostic Arm):

1. Acute injury in the last 12 weeks.
2. Age under 25.
3. Severe degenerative changes of painful joint (shoulder, hip or knee).
4. History of arthroplasty or metallic implant within the painful joint.
5. Severe gadolinium contrast allergy.
6. Severe renal disease or ongoing dialysis.
7. History of malignancy with life expectancy of less than one year, or malignancy with known bone metastasis.
8. Current pregnancy.
9. Formal diagnosis of cognitive impairment.

Exclusion Criteria (Therapeutic Arm):

1. Severe iodinated contrast allergy.
2. Severe coronary or peripheral arterial disease.
3. Coagulopathy.
4. Uncontrolled type 2 diabetes or diabetic neuropathy.
5. History of seizures or other severe complication from conscious sedation.
6. Prior upper or lower extremity arterial bypass.
7. Ongoing participation in another interventional (therapeutic) trial for chronic joint pain.
8. Lack of peri-articular hypervascularity on initial perfusion MRI.
9. All exclusion criteria for the Diagnostic Arm.

Primary outcomes:
measure: Primary Clinical Outcome (Hip and Knee, Therapeutic Arm Only)
timeFrame: Score obtained at follow-up visit 6 months after intervention
measure: Primary Clinical Outcome (Shoulder, Therapeutic Arm Only)
timeFrame: Score obtained at follow-up visit 6 months after intervention
measure: Primary Imaging Outcome (Therapeutic Arm Only)
timeFrame: Research MRI obtained 3 months after intervention
Secondary outcomes:
measure: Secondary Clinical Outcome (Hip and Knee, Diagnostic Arm Only)
timeFrame: Score obtained at follow-up visit after 12 months
measure: Secondary Clinical Outcome (Shoulder, Diagnostic Arm Only)
timeFrame: Score obtained at follow-up visit after 12 months
measure: Secondary Imaging Outcome (Diagnostic Arm Only)
timeFrame: Research MRI obtained after 12 months of follow-up
measure: Secondary Imaging Outcome 2 (Diagnostic Arm Only)
timeFrame: Research MRI obtained after 12 months of follow-up
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: VA Palo Alto Healthcare System
state: California
Study officials:
affiliation: VA Palo Alto Health Care System
name: Sirish Kishore, MD
role: PRINCIPAL_INVESTIGATOR
References: