Clinical trial NCT04405297: A Disease-based Treatment Study for Diagnosed Osteoarthritis Utilizing Adipose-derived Regenerative Cells
Official title: A Disease-based Treatment Study for Diagnosed Osteoarthritis Utilizing Adipose-derived Regenerative Cells
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Knee Osteoarthritis
Hip Osteoarthritis
Ankle Osteoarthritis
Shoulder Osteoarthritis
Wrist Osteoarthritis
Keywords: Stem Cells
Adipose-derived regenerative cells
Osteoarthritis
Adipose-derived stem cells
Arthritis
Joint Diseases
Lead sponsor: Sanford Health
Sponsor class: OTHER
First posted: 2020-05-28
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The focus of this study is to investigate the therapeutic benefit of autologous ADRCs in patients with OA in various joints. The ENDURE study allows subjects at Sanford Health and in the United States access to adipose-derived regenerative cells while reviewing safety for subjects with knee, shoulder, hip, ankle and wrist OA, using a more pragmatic and standard clinical approach.

Brief summary: This is a prospective, multi-location safety and effectiveness study, and data registry of autologous adult ADRCs generated by the Transpose® RT System in subjects with OA in the shoulder, wrist, knee, hip, or ankle.

Detailed description: Subjects who have signed informed consent and Health Insurance Portability and Accountability Act (HIPPA) authorization, and are determined to meet all inclusion criteria and no exclusion criteria will be enrolled in this study and receive the ADRC treatment.

The subject will have an injection procedure (ADRC treatment) For this study, a licensed physician trained in liposuction must perform the syringe liposuction procedure. The licensed physician who performs the lipoplasty may be the Investigator or a non-Investigator physician (e.g., a plastic surgeon) who is trained on the study protocol.

All subjects will undergo a minor syringe liposuction procedure to acquire approximately 100 mL of lipoaspirate for preparation of ADRC using the Transpose® RT System. The removed tissue is processed to extract a cell suspension (the cell product). Once the cell product has been obtained, tested, and found to conform to release criteria, the subject will be treated with the ADRCs.

Eligibility criteria: All Cohorts:

To be eligible to participate in this study, a subject must meet all the following criteria.

Inclusion Criteria-ALL Cohorts:

1. Men and women age 18 or older
2. Clinical and radiographic diagnosis of OA in one of the following areas: Ankle, Hip, Knee, Shoulder, or Wrist
3. Continued OA pain in the targeted joint despite conservative measures (per treating provider's discretion)
4. Average daily VAS Pain Score ≥3
5. Understand and provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization prior to initiation of any study-specific procedures
6. On physical exam. subject appears to have adequate adipose tissue for liposuction
7. Subject must also meet additional inclusion criteria specific to the targeted joint cohort

Ankle Cohort:

1. Currently Kellgren-Lawrence Grade II, III or IV in the ankle based on X-ray (weight-bearing mortise views with 20⁰ internal rotation)
2. Ankle pain for at least 6 months, despite conservative treatment or inability to tolerate the side effects of medications
3. Normal activity level, not bedridden or confined to a wheelchair, able to walk 30 meters without the aid of a walker, crutches or cane

Hip Cohort:

1. Hip OA diagnosed on x-ray and/or Magnetic Resonance Imaging (MRI) (Tӧnnis grade 1, 2, or 3)

Knee Cohort:

1. Kellgren-Lawrence system of Grade II, III, or IV
2. Subject may have concomitant patellofemoral but they must have stage II or higher generalized knee OA

Shoulder Cohort:

1. Grades 1, 2 or 3 OA in the index glenohumeral joint based on the Samilson-Prieto classification system as confirmed by X-ray (axillary view and true anterior-posterior view)
2. Subjects who have failed standard non-surgical management of their shoulder arthritis who would benefit from a shoulder arthroplasty. Failed medical management will be defined as persistent pain and disability despite adequate standard non-operative management for 6 months. Medical management will be defined as:

   1. The use of drugs including analgesics and non-steroidal anti-inflammatory drugs
   2. Activity modification

Wrist Cohort:

1. Clinical symptoms consistent with wrist OA

Exclusion Criteria- ALL Cohorts:

1. Subject cannot meet any of the exclusion criteria listed of the targeted joint cohort
2. Viscosupplementation within 6 months of screening in the targeted joint
3. Other Biologic Injection (Platelet Rich Plasma (PRP) or stem cell) within 6 months in the targeted joint
4. Surgery in the targeted joint within the past 6 months (either open or scope)
5. Planned/anticipated surgery of the targeted joint during study participation
6. Systemic or intra-articular injection of corticosteroids in any joint within 3 months before screening (re-screening allowed once this criteria is met)
7. Females of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study. Oral, injected or implanted hormonal contraceptive, barrier methods (condom or diaphragm with spermicide), intrauterine device, surgical sterilization, transdermal delivery, congenital sterility or sexual abstinence are considered acceptable forms of birth control. If sexually active, the subject must have been using one of the accepted birth control methods at least one month prior to study entry.
8. Part of a vulnerable population per Office for Human Research Protections (OHRP) definition (pregnant women and breast-feeding women, cognitively impaired, prisoners, etc.)
9. Unwilling to discontinue the use of Non-Steroidal Anti-Inflammatory (NSAID)s for 7 calendar days prior to the procedure
10. Unwilling to discontinue NSAIDS for 5 calendar days after procedure
11. Insufficient amount of subcutaneous tissue to allow recovery of at least 100mL of lipoaspirate
12. Diagnosed musculoskeletal cancer or any diagnosed cancer, other than musculoskeletal if not on long term remission (e.g. at least 5 years or negative biopsy at last exam), except basal cell carcinoma
13. Have received chronic (more than 7 consecutive days) treatment with systemic corticosteroids at a dose equivalent to prednisone ≥ 10 mg/day within 14 days prior to an injection procedure.
14. Subject is currently participating in another clinical trial that has not yet completed its primary endpoint. (Nonintervention observational studies are not exclusionary.)
15. History of, or ongoing, autoimmune disorder that requires treatment with an immunosuppressive medication
16. Subjects who have a documented history or presence of inflammatory arthritis, rheumatoid arthritis, and sepsis in the treatment site
17. History of bleeding disorders or inflammatory joint disease
18. Inability to hold anti-platelet therapy according to treating provider prior to procedure
19. Any medical condition that could preclude participation in the study in the opinion of the investigator
20. Active workers' compensation case in progress with the targeted joint
21. Daily opioid use for the 3 months prior to screening or anticipated daily use while participating on study
22. Psychiatric disorder that may prevent participation in the study in the opinion of the investigators
23. A positive screen for human immunodeficiency virus (HIV) by antibodies or nucleic acid test
24. Has a known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA \[qualitative\] is detected)
25. Allergy to sodium citrate of any "caine" type of local anesthetic
26. Hemoglobin less than 10g/dL at the time of screening
27. Leukocytes \<3,000/µL; neutrophils \<1,500/µL; lymphocytes \<800/µL; platelets \<100,000/µL at the time of screening
28. Subjects with a known diagnosis of osteoporosis
29. Diagnosis of liver disease as defined by alanine aminotransferase (ALT) \>2x the upper limit of age-determined normal (ULN) or total bilirubin \> 1.5x ULN

Ankle Cohort:

1. Lower leg trauma in a location other than within the ankle
2. Arthroscopy or open surgery of the ankle joint within 6 months of screening.
3. Extreme obesity, as defined by National Institutes of Health (NIH) Clinical Guidelines Body Mass Index (BMI \> 40)
4. Any condition other than OA of the ankle joint which, in the opinion of the investigator, affects their ability to ambulate to a sufficient degree to interfere with the assessment of the safety and treatment effects of the study injection.

Hip Cohort:

1. Evidence of hip dysplasia (centre edge angle less than 20⁰)
2. Previous fracture trauma to the affected hip requiring medical or surgical treatment
3. Severe acetabular deformities (e.g. acetabular protrusion, coxa profunda, circumferential labral ossification)
4. Infections or skin diseases at target hip joint
5. Significant medical co-morbidities (requiring daily assistance for activities of daily living)
6. Any clinically significant or symptomatic vascular or neurologic disorder of the lower extremities
7. Extreme obesity, as defined by NIH Clinical Guidelines Body Mass Index (BMI\>40)
8. Femoral head deformity (perthes or AVN)

Knee Cohort:

1. Extreme obesity, as defined by NIH Clinical Guidelines Body Mass Index (BMI\>40)
2. Clinically apparent tense effusion of the targeted knee
3. Significant valgus/varus deformities (+/- 10⁰)

Shoulder Cohort:

1. Walch B2 glenoid with greater than 10⁰ of retroversion
2. Active joint or systemic infection
3. Rotator cuff arthropathy
4. Significant muscle paralysis
5. Charcot's arthropathy

Wrist Cohort:

1. Subjects who have a documented diagnosis of active carpal tunnel syndrome

Primary outcomes:
measure: Safety as indicated by incidence (%) of unanticipated AEs. All AEs and SAEs will be graded on severity by the Investigator using the National Institutes of Health Common Terminology Criteria for Adverse Events (NIH CTCAE).
timeFrame: Up to 2 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the knee using PROMIS 10 Global health
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the knee using SF-12v2
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the knee using the Visual Analog Pain Scale (VAS-Pain)
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the knee using the Knee Osteoarthritis Outcome Score (KOOS)
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in the range of motion of the knee (ROM) measurements for the knee
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the shoulder using PROMIS 10 Global health
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the shoulder using SF-12v2
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the shoulder using the Visual Analog Pain Scale (VAS-Pain)
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the shoulder using American Surgeon and Elbow Surgeon (ASES) measure
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the shoulder using the Oxford Shoulder Score
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in the range of motion of the shoulder (ROM)
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the wrist using PROMIS 10 Global health
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the wrist using SF-12v2
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the wrist using the Pain Score Analog Scale (VAS-Pain)
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the wrist using the Quick-Dash
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the wrist using PROMIS-Upper Extremity
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in the range of motion of the wrist (ROM)
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the ankle using PROMIS 10 Global health
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the ankle using SF-12v2
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the ankle using the Pain Score on Visual Analog (VAS-Pain)
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the ankle using the Foot and Ankle Disability Index (FADI)
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in the range of motion of the ankle (ROM)
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the hip using PROMIS 10 Global health
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the hip using SF-12v2
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the hip using Pain Score on Visual Analog Scale (VAS-Pain)
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in patient reported outcomes (PRO) measurements for the hip using the Hip Disability Osteoarthritis Outcome Score (HOOS)
timeFrame: Through study completion, up to 3 years
measure: Efficacy outcomes include changes in the range of motion of the knee (ROM) measurements for the hip
timeFrame: Through study completion, up to 3 years
Secondary outcomes:
measure: The secondary objective is to create a data registry for future research on ADRC use for OA
timeFrame: Through study completion, up to 3 years
Other outcomes:
measure: A small volume of each subject's ADRC will be processed and stored for future research.
timeFrame: Through study completion, up to 3 years
Locations:
city: Sioux Falls
country: United States
facility: Sanford Orthopedics and Sports Medicine
state: South Dakota
Study officials:
affiliation: Sanford Health
name: David A. Pearce, PhD
role: PRINCIPAL_INVESTIGATOR
References: