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Evaluation of Safety and Efficacy of Wharton's Jelly Compared to Hyaluronic Acid and Saline for Knee Osteoarthritis.

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ClinicalTrials.gov Identifier: NCT04711304
Recruitment Status : Not yet recruiting
First Posted : January 15, 2021
Last Update Posted : July 20, 2021
Sponsor:
Information provided by (Responsible Party):
BioIntegrate

Brief Summary:
The purpose of this study is to determine the safety and efficacy of intraarticular injection of umbilical cord derived Wharton's Jelly compared to hyaluronic acid and saline for treatment of knee osteoarthritis symptoms.

Condition or disease Intervention/treatment Phase
Osteoarthritis, Knee Biological: Umbilical Cord-derived Wharton's Jelly Device: Hyaluronic acid Other: Saline Phase 1 Phase 2

Detailed Description:

Osteoarthritis (OA) is the most common joint disorder in the United States (US), affecting approximately 12% (~30 million) of US adults aged between 25 and 74 years. By 2030, the number of US adults with arthritis is expected to reach 67 million leading to continuous increase in number of total knee replacement surgeries. While total knee replacement surgeries have shown advantages, avoiding or delaying surgery appears desirable, both from medical and health care system perspective. Lowering the number of total knee replacement surgeries will also lead to a reduced number of costly revision surgeries. Published studies have also demonstrated that the outcomes after total knee replacement surgeries for patients with Grade II or III knee OA (on Kellgren-Lawrence scale) are worse compared to patients with Grade IV OA. Additionally, conventional treatment modalities including activity modification, physical therapy, pharmacological agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, viscosupplementation and narcotics have limitations and potential side effects. Thus, there is a need for alternative intervention for patients with Grade II or III knee OA.

Interest in the use of biologics for regenerative medicine applications has increased over the last decade. To be compliant in the United States (U.S.), biologics that adhere to the U.S. Food and Drug Administration (FDA) regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/P's) regulated under title 21, part 1271 of the Code of Federal Regulations (CFR) must meet all the conditions under section 361 of Public Health Safety (PHS) Act to be regulated solely under this section. According to this regulation, HCT/P's must meet the criteria of being minimally manipulated, for homologous use only, not to be combination products, to have no systemic effect, and to be non-dependent on the metabolic activity of the living cells. Despite increased use, there is insufficient literature assessing the amount of growth factors (GF), cytokines (CK), hyaluronic acid (HA) and extracellular vesicles (EV) including exosomes present in these products, and more specifically, umbilical cord derived Wharton's Jelly. In addition, there is limited or no literature assessing the safety and efficacy of umbilical cord derived Wharton's Jelly products via a randomized, controlled, multi-center study.

To address the insufficient literature assessing the presence and quantity of GF, CK, HA and EV including exosomes, investigators formulated a novel umbilical cord derived Wharton's Jelly product and evaluated it for the presence of these factors. The results from this study demonstrated that the essential components of regenerative medicine, namely GF, CK, HA and EV, are all present in large quantities in the formulated Wharton's Jelly. This study was an essential preliminary step to better characterize this Wharton's Jelly formulation before performing clinical trials to determine safety and efficacy of this novel formulation for regenerative medicine applications including for providing symptomatic relief to patients with Grade II or III knee OA.

The goal of the proposed study is to evaluate the safety and efficacy of intraarticular injection of umbilical cord derived Wharton's Jelly for treatment of knee osteoarthritis symptoms. Investigators hypothesize that there will be no difference in patients receiving injection of umbilical cord derived Wharton's Jelly, HA or saline with respect to safety. Investigators also hypothesize that patients receiving intraarticular injection of Wharton's Jelly will show an improvement in their overall satisfaction, Numeric Pain rating Scale (NPRS), Knee Injury and Osteoarthritis Outcome Score (KOOS) and cartilage formation over a period of 1 year compared to the baseline visit. Our null hypothesis is that there is no difference in patients receiving either Wharton's Jelly, hyaluronic acid or saline; and no difference between the baseline and after-treatment within each treatment group over a period of 1 year.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 168 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Randomized, Controlled, Single-blind, Multi-center Trial to Evaluate the Safety and Efficacy of Intraarticular Injection of Umbilical Cord Derived Wharton's Jelly Compared to Hyaluronic Acid and Saline for Knee Osteoarthritis.
Estimated Study Start Date : January 1, 2022
Estimated Primary Completion Date : June 1, 2025
Estimated Study Completion Date : June 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Experimental: Wharton's Jelly
Intraarticular injection of Wharton's Jelly
Biological: Umbilical Cord-derived Wharton's Jelly
Intraarticular injection

Active Comparator: Hyaluronic Acid
Intraarticular injection of Hyaluronic Acid
Device: Hyaluronic acid
Intraarticular injection

Placebo Comparator: Saline
Intraarticular injection of Saline
Other: Saline
Intraarticular injection




Primary Outcome Measures :
  1. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: Immediately after injection ]
    To determine safety i.e. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.

  2. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 24hours after injection ]
    To determine safety i.e. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.

  3. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 48hours after injection ]
    To determine safety i.e. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.

  4. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 1week after injection ]
    To determine safety i.e. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.

  5. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 6weeks after injection ]
    To determine safety i.e. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.

  6. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 3Months after injection ]
    To determine safety i.e. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.

  7. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 6Months after injection ]
    To determine safety i.e. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.

  8. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 1Year after injection ]
    To determine safety i.e. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.

  9. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 1week after injection ]
    To determine patient satisfaction via 7-point Likert Scale. An increase in score indicates improvement.

  10. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 6weeks after injection ]
    To determine patient satisfaction via 7-point Likert Scale. An increase in score indicates improvement.

  11. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 3Months after injection ]
    To determine patient satisfaction via 7-point Likert Scale. An increase in score indicates improvement.

  12. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 6Months after injection ]
    To determine patient satisfaction via 7-point Likert Scale. An increase in score indicates improvement.

  13. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: 1Year after injection ]
    To determine patient satisfaction via 7-point Likert Scale. An increase in score indicates improvement.

  14. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: Change from baseline to 3Months after injection ]
    To determine patient satisfaction via 36-item short form survey (SF36)

  15. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: Change from baseline to 6Months after injection ]
    To determine patient satisfaction via 36-item short form survey (SF36)

  16. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly [ Time Frame: Change from baseline to 1Year after injection ]
    To determine patient satisfaction via 36-item short form survey (SF36)


Secondary Outcome Measures :
  1. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Change from baseline to immediately after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS)

  2. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and immediately after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  3. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Change from baseline to 24hours after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  4. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 24hours after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  5. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Change from baseline to 48hours after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  6. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 48hours after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  7. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Change from baseline to 1week after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  8. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 1week after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  9. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Change from baseline to 6weeks after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  10. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 6weeks after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  11. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Change from baseline to 3Months after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  12. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 3Months after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  13. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Change from baseline to 6Months after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  14. Change in patient reported outcome measures, Numeric Pain Rating Scale [ Time Frame: Change from baseline to 1year after injection ]
    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

  15. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score [ Time Frame: Change from baseline to 1week after injection ]
    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

  16. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score [ Time Frame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for KOOS from baseline and 1week after injection ]
    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

  17. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score [ Time Frame: Change from baseline to 6weeks after injection ]
    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

  18. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score [ Time Frame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for KOOS from baseline and 6weeks after injection ]
    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

  19. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score [ Time Frame: Change from baseline to 3Months after injection ]
    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

  20. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score [ Time Frame: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for KOOS from baseline and 3Months after injection ]
    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

  21. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score [ Time Frame: Change from baseline to 6Months after injection ]
    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

  22. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score [ Time Frame: Change from baseline to 1Year after injection ]
    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

  23. Cartilage Formation [ Time Frame: Change from baseline to 1year after injection ]
    To assess cartilage formation via MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue). An increase in score indicates improvement.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must be 18 years or older.
  2. Must have a body mass index (BMI) of < 50Kg/m2.
  3. Must be able to comply with the requirements of study visits.
  4. Diagnosed with mild to moderate knee osteoarthritis (OA) in one knee only - Grade 2 or 3 on the Kellgren Lawrence (KL) grading scale.
  5. Pain score of 4 or more on the NPRS (on scale of 0 to 10).
  6. Female patients were abstinent, surgically sterilized or postmenopausal.
  7. Premenopausal females with negative pregnancy test, and who does not anticipate pregnancy and will actively practice an accepted contraceptive method for the duration of study.
  8. Males with premenopausal female partners, will take contraceptive measures for the duration of study.
  9. Be willing and capable of giving written informed consent to participate in this clinical study.
  10. Be willing and capable of complying with study-related requirements, procedures and visits.

Exclusion Criteria:

  1. Patients who have taken any pain medications including NSAIDs within 2 weeks, prior to the study injection date, regularly use anticoagulants, substance abuse history, and/or failure to agree not to take any knee-symptom modifying drugs during the course of the study without discussing and reporting the use to site principal investigator and study team.
  2. Patients who are positive on special tests and stability tests on the physical exam case report form.
  3. Patients with intraarticular injection of any drug including corticosteroids, viscosupplementation in the index knee in last 3 months.
  4. Patients with index knee surgery within last 6 months.
  5. Patients with traumatic injury to index knee within last 3 months.
  6. Patients with planned elective surgery during the course of the study.
  7. Patients with organ or hematologic transplantation history, rheumatoid arthritis or other autoimmune disorders.
  8. Patients on immunosuppressive medication/treatment, diagnosis of non-basal cell carcinoma within last 5 years.
  9. Patients with knee infection or who used antibiotics for knee infection within last 3 months.
  10. Patients who participated in another clinical trial or treatment with any investigational product within last 30 days prior to inclusion in the study.
  11. Female patients who are breast feeding or are pregnant or desire to be pregnant during the course of the study.
  12. Patients with contraindication to X-ray or MRI imaging.
  13. Patients with serious neurological, psychological or psychiatric disorders.
  14. Patients with other medical conditions determined by site principal investigator as interfering with the study.
  15. Patients with an injury or disability claim under current litigation or pending or approved workers' compensation claim.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04711304


Contacts
Layout table for location contacts
Contact: Saadiq F. El-Amin III, MD, PhD 678-257-7078 dr.saadiqelamin@gmail.com
Contact: Ashim Gupta, PhD, MBA agupta@biointegrate.com

Sponsors and Collaborators
BioIntegrate
Investigators
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Principal Investigator: Saadiq F. El-Amin III, MD, PhD El-Amin Orthopaedic & Sports Medicine Institute
Study Director: Ashim Gupta, PhD, MBA BioIntegrate
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: BioIntegrate
ClinicalTrials.gov Identifier: NCT04711304    
Other Study ID Numbers: BIOINT - 2020WJ/OA
First Posted: January 15, 2021    Key Record Dates
Last Update Posted: July 20, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioIntegrate:
Knee Osteoarthritis, Umbilical Cord, Wharton's Jelly
Additional relevant MeSH terms:
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Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Hyaluronic Acid
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Viscosupplements
Protective Agents