Clinical trial NCT06608134: Safety and Feasibility of Umbilical Cord Wharton's Jelly Allograft Injections for Knee Osteoarthritis
Official title: Safety and Feasibility of Umbilical Cord Wharton's Jelly Allograft Injections for
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Osteoarthritis, Knee
Keywords: umbilical cord
Whartons Jelly
Allograft
knee pain
knee arthritis
Lead sponsor: R3 Medical Research
Sponsor class: INDUSTRY
First posted: 2024-09-23
Enrollment: 120
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, prospective, open label, dose escalation, non-controlled
Primary purpose: TREATMENT

Brief summary: This is a Pilot Study which is randomized, prospective, open label, dose escalation, non-controlled evaluating safety and feasibility of intra-articular Wharton's Jelly (WJ) allograft will be evaluated in patients suffering with knee osteoarthritis. The participants will be randomized to one of three dosing treatment arms that will consist of one intra-articular knee injection containing either low dose, medium dose or high dose WJ allograft tissue.

Detailed description: This is a Pilot Study which is randomized, prospective, open label, dose escalation, non-controlled study in which the safety and feasibility of intra-articular Wharton's Jelly (WJ) allograft will be evaluated in patients suffering with knee OA. The participants will be randomized to one of three dosing treatment arms that will consist of one intra-articular knee injection containing either low dose, medium dose or high dose WJ allograft tissue.

As this is a Pilot Study primarily designed to evaluate safety, no control will be used. The dosing groups will consist of either 2cc WJ Allograft (Low Dose), 3cc WJ Allograft (Medium Dose), or 4cc WJ Allograft (High Dose) with 120 total patients randomized into the three arms equally. In addition to baseline outcome instruments along with imaging and laboratory studies, patients will be followed for one year for evaluation of safety, pain relief and functional improvements.

Eligibility criteria: Inclusion Criteria:

* Be over age 30
* Diagnosed with Grade II or III OA on the KL scale (in one knee).
* Body Mass Index (BMI) \<50Kg/m2
* Pain score of 4 or more on the Numeric Pain Rating Scale (NPRS)
* Female patients must be abstinent, surgically sterilized or postmenopausal
* Premenopausal females must have a negative pregnancy test, on contraceptive measures and do not anticipate pregnancy during the duration of the study.
* Be willing and capable of giving written informed consent to participate in English.
* Be willing and capable of complying with study-related requirements, procedures and visits in English.

Exclusion Criteria:

* Have taken any pain medication including nonsteroidal anti-inflammatory drugs (NSAIDs) within 2 weeks prior to study injection date.
* Use anticoagulants have a substance abuse history and fail to agree not to take any knee-symptom modifying drugs during the course of the study without discussing and reporting the use to the site principal investigator and study team.
* Have had an intra-articular injection of any drug including viscosupplementation in the index knee in the past 6 months.
* Have had surgery on the index knee with the past 6 months.
* Had a traumatic injury to the index knee with the past 3 months.
* Planned elective surgery during the course of the study.
* A history of organ or hematologic transplantation, rheumatoid arthritis, or other autoimmune disorders.
* Be on immunosuppressive medications.
* Have a diagnosis of carcinoma with the past 2 years.
* Have a knee infection or have used antibiotics for knee infection within the past 3 months.
* Have participated in any other clinical trial or treatment (not just for the knee, but for any reason) with any investigational product within the past 30 days prior to inclusion of study.
* Female patients who are breast feeding or are pregnant or desire to become pregnant during the course of the study.
* Contraindications to radiographic or MRI imaging.
* Serious neurological, psychological or psychiatric disorders.
* Injury or disability claims under current litigation or pending or approved workers compensation claims.
* Have a known drug allergy to amphotericin-B, ciprofloxacin, gentamycin, penicillin, or streptomycin.

Primary outcomes:
measure: C Reactive Protein
timeFrame: Baseline, 1 week after the procedure, 6 weeks, 3 months, 6 months and one year
measure: Erythrocyte Sedimentation Rate
timeFrame: Baseline, 1 week after the procedure, 6 weeks, 3 months, 6 months and one year
measure: Alanine Transaminase
timeFrame: Baseline, 1 week after the procedure, 6 weeks, 3 months, 6 months and one year
measure: Aspartate Transaminase
timeFrame: Baseline, 1 week after the procedure, 6 weeks, 3 months, 6 months and one year
measure: Alkaline Phosphatase
timeFrame: Baseline, 1 week after the procedure, 6 weeks, 3 months, 6 months and one year
measure: Albumin
timeFrame: Baseline, 1 week after the procedure, 6 weeks, 3 months, 6 months and one year
measure: Creatinine
timeFrame: Baseline, 1 week after the procedure, 6 weeks, 3 months, 6 months and one year
measure: Blood Urea Nitrogen
timeFrame: Baseline, 1 week after the procedure, 6 weeks, 3 months, 6 months and one year
Secondary outcomes:
measure: 36-Item Short Form Survey (SF-36)
timeFrame: Baseline, 24 hours after intervention, 1 week, 6 weeks, 3 months, 6 months, 1 year
measure: Numerical Pain Rating Scale (NPRS)
timeFrame: Baseline, 24 hours after intervention, 1 week, 6 weeks, 3 months, 6 months, 1 year
measure: Knee Injury and Osteoarthritis Outcome Score
timeFrame: Baseline, 24 hours after intervention, 1 week, 6 weeks, 3 months, 6 months, 1 year
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: R3 Anti Aging Scottsdale
state: Arizona
city: Beverly Hills
country: United States
facility: R3 Anti Aging Beverly Hills
state: California
city: Fresno
country: United States
facility: Optimal Medical Group
state: California
city: New York
country: United States
facility: Scheer Medical Wellness
state: New York
city: Cleveland
country: United States
facility: Dr. Duc (Steve) Le, MD
state: Texas
Study officials:
References:
citation: Cisternas MG, Murphy L, Sacks JJ, Solomon DH, Pasta DJ, Helmick CG. Alternative Methods for Defining Osteoarthritis and the Impact on Estimating Prevalence in a US Population-Based Survey. Arthritis Care Res (Hoboken). 2016 May;68(5):574-80. doi: 10.1002/acr.22721.
citation: Van Manen MD, Nace J, Mont MA. Management of primary knee osteoarthritis and indications for total knee arthroplasty for general practitioners. J Am Osteopath Assoc. 2012 Nov;112(11):709-15.
citation: Losina E, Thornhill TS, Rome BN, Wright J, Katz JN. The dramatic increase in total knee replacement utilization rates in the United States cannot be fully explained by growth in population size and the obesity epidemic. J Bone Joint Surg Am. 2012 Feb 1;94(3):201-7. doi: 10.2106/JBJS.J.01958.
citation: Gupta A, Potty ASR, Ganta D, Mistovich RJ, Penna S, Cady C, Potty AG. Streamlining the KOOS Activities of Daily Living Subscale Using Machine Learning. Orthop J Sports Med. 2020 Mar 24;8(3):2325967120910447. doi: 10.1177/2325967120910447. eCollection 2020 Mar.
citation: Farr J, Gomoll AH, Yanke AB, Strauss EJ, Mowry KC; ASA Study Group. A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. J Knee Surg. 2019 Nov;32(11):1143-1154. doi: 10.1055/s-0039-1696672. Epub 2019 Sep 18.
citation: Hoorntje A, Witjes S, Koenraadt KLM, Aarts R, Weert T, van Geenen RCI. More Severe Preoperative Kellgren-Lawrence Grades of Knee Osteoarthritis were Partially Associated with Better Postoperative Patient-Reported Outcomes in TKA Patients. J Knee Surg. 2019 Mar;32(3):211-217. doi: 10.1055/s-0038-1635114. Epub 2018 Feb 28.
citation: Kahn TL, Soheili A, Schwarzkopf R. Outcomes of total knee arthroplasty in relation to preoperative patient-reported and radiographic measures: data from the osteoarthritis initiative. Geriatr Orthop Surg Rehabil. 2013 Dec;4(4):117-26. doi: 10.1177/2151458514520634.
citation: Eyichukwu GO. Non-Steroidal anti inflammatory drugs usage in orthopaedics and trauma practice. A guide and review. Niger J Med. 2010 Oct-Dec;19(4):374-81. doi: 10.4314/njm.v19i4.61959.
citation: Yasir M, Goyal A, Sonthalia S. Corticosteroid Adverse Effects. 2023 Jul 3. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK531462/
citation: Gupta A, Woods MD, Illingworth KD, Niemeier R, Schafer I, Cady C, Filip P, El-Amin SF 3rd. Single walled carbon nanotube composites for bone tissue engineering. J Orthop Res. 2013 Sep;31(9):1374-81. doi: 10.1002/jor.22379. Epub 2013 Apr 29.
citation: Lamplot JD, Rodeo SA, Brophy RH. A Practical Guide for the Current Use of Biologic Therapies in Sports Medicine. Am J Sports Med. 2020 Feb;48(2):488-503. doi: 10.1177/0363546519836090. Epub 2019 Apr 30.
citation: Rodriguez HC, Gupta M, Cavazos-Escobar E, El-Amin SF 3rd, Gupta A. Umbilical cord: an allogenic tissue for potential treatment of COVID-19. Hum Cell. 2021 Jan;34(1):1-13. doi: 10.1007/s13577-020-00444-5. Epub 2020 Oct 9.
citation: Gupta A, Cady C, Fauser AM, Rodriguez HC, Mistovich RJ, Potty AGR, Maffulli N. Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine Applications. Int J Mol Sci. 2020 Dec 9;21(24):9364. doi: 10.3390/ijms21249364.
citation: Main BJ, Maffulli N, Valk JA, Rodriguez HC, Gupta M, El-Amin SF 3rd, Gupta A. Umbilical Cord-Derived Wharton's Jelly for Regenerative Medicine Applications: A Systematic Review. Pharmaceuticals (Basel). 2021 Oct 27;14(11):1090. doi: 10.3390/ph14111090.
citation: Gupta A, El-Amin SF 3rd, Levy HJ, Sze-Tu R, Ibim SE, Maffulli N. Umbilical cord-derived Wharton's jelly for regenerative medicine applications. J Orthop Surg Res. 2020 Feb 13;15(1):49. doi: 10.1186/s13018-020-1553-7.
citation: Dernek B, Duymus TM, Koseoglu PK, Aydin T, Kesiktas FN, Aksoy C, Mutlu S. Efficacy of single-dose hyaluronic acid products with two different structures in patients with early-stage knee osteoarthritis. J Phys Ther Sci. 2016 Nov;28(11):3036-3040. doi: 10.1589/jpts.28.3036. Epub 2016 Nov 29.