AzTrials
AzTrials

Osteoarthritis, KneePhase 1/2NCT04711304

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

A Phase 1/2 study testing Umbilical Cord-derived Wharton's Jelly, Hyaluronic acid and Saline in people with Osteoarthritis, Knee, run by BioIntegrate.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Osteoarthritis, Knee
What is being tested?
Umbilical Cord-derived Wharton's Jelly, Hyaluronic acid and Saline
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
168 participants
Where
No sites listed yet
Study dates
1 Jan 2023to 1 Jun 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must be 18 years or older.
  • Must have a body mass index (BMI) of < 50Kg/m2.
  • Must be able to comply with the requirements of study visits.
  • Diagnosed with mild to moderate knee osteoarthritis (OA) in one knee only - Grade 2 or 3 on the Kellgren Lawrence (KL) grading scale.
  • Pain score of 4 or more on the NPRS (on scale of 0 to 10).
  • Female patients were abstinent, surgically sterilized or postmenopausal.
Show all 10Show fewer
  • 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.
  • Males with premenopausal female partners, will take contraceptive measures for the duration of study.
  • Be willing and capable of giving written informed consent to participate in this clinical study.
  • Be willing and capable of complying with study-related requirements, procedures and visits.

Who cannot join

  • 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.
  • Patients who are positive on special tests and stability tests on the physical exam case report form.
  • Patients with intraarticular injection of any drug including corticosteroids, viscosupplementation in the index knee in last 3 months.
  • Patients with index knee surgery within last 6 months.
  • Patients with traumatic injury to index knee within last 3 months.
  • Patients with planned elective surgery during the course of the study.
Show all 15Show fewer
  • Patients with organ or hematologic transplantation history, rheumatoid arthritis or other autoimmune disorders.
  • Patients on immunosuppressive medication/treatment, diagnosis of non-basal cell carcinoma within last 5 years.
  • Patients with knee infection or who used antibiotics for knee infection within last 3 months.
  • Patients who participated in another clinical trial or treatment with any investigational product within last 30 days prior to inclusion in the study.
  • Female patients who are breast feeding or are pregnant or desire to be pregnant during the course of the study.
  • Patients with contraindication to X-ray or MRI imaging.
  • Patients with serious neurological, psychological or psychiatric disorders.
  • Patients with other medical conditions determined by site principal investigator as interfering with the study.
  • Patients with an injury or disability claim under current litigation or pending or approved workers' compensation claim.

Trial locations and contacts

No sites are listed yet.

Saadiq F. El-Amin III, MD, PhD contact

678-257-7078

dr.saadiqelamin@gmail.com

Ashim Gupta, PhD, MBA contact

agupta@biointegrate.com

About this study

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.

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.

Read the 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.

Being tested
Umbilical Cord-derived Wharton's Jelly, Hyaluronic acid, Saline
Keywords
Knee Osteoarthritis, Umbilical Cord, Wharton's Jelly
Medical subject headings
Osteoarthritis, Knee

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Umbilical Cord-derived Wharton's JellyBiological

    Intraarticular injection

  • Hyaluronic acidDevice

    Intraarticular injection

  • SalineOther

    Intraarticular injection

Study groups in NCT04711304
Study groupRoleWhat they receive
Wharton's JellyExperimentalIntraarticular injection of Wharton's Jelly
Receives: Biological: Umbilical Cord-derived Wharton's Jelly
Hyaluronic AcidActive comparatorIntraarticular injection of Hyaluronic Acid
Receives: Device: Hyaluronic acid
SalinePlacebo comparatorIntraarticular injection of Saline
Receives: Other: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    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.

    Measured: Immediately after injection

  2. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    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.

    Measured: 24hours after injection

  3. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    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.

    Measured: 48hours after injection

  4. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    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.

    Measured: 1week after injection

  5. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    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.

    Measured: 6weeks after injection

  6. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    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.

    Measured: 3Months after injection

  7. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    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.

    Measured: 6Months after injection

  8. Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    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.

    Measured: 1Year after injection

  9. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    To determine patient satisfaction via 7-point Likert Scale. An increase in score indicates improvement.

    Measured: 1week after injection

  10. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    To determine patient satisfaction via 7-point Likert Scale. An increase in score indicates improvement.

    Measured: 6weeks after injection

  11. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    To determine patient satisfaction via 7-point Likert Scale. An increase in score indicates improvement.

    Measured: 3Months after injection

  12. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    To determine patient satisfaction via 7-point Likert Scale. An increase in score indicates improvement.

    Measured: 6Months after injection

  13. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    To determine patient satisfaction via 7-point Likert Scale. An increase in score indicates improvement.

    Measured: 1Year after injection

  14. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    To determine patient satisfaction via 36-item short form survey (SF36)

    Measured: Change from baseline to 3Months after injection

  15. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    To determine patient satisfaction via 36-item short form survey (SF36)

    Measured: Change from baseline to 6Months after injection

  16. Patient Satisfaction associated with intraarticular administration of umbilical cord-derived Wharton's Jelly

    To determine patient satisfaction via 36-item short form survey (SF36)

    Measured: Change from baseline to 1Year after injection

Secondary outcomes (23)
  1. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS)

    Measured: Change from baseline to immediately after injection

  2. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and immediately after injection

  3. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Change from baseline to 24hours after injection

  4. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 24hours after injection

  5. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Change from baseline to 48hours after injection

  6. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 48hours after injection

  7. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Change from baseline to 1week after injection

  8. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 1week after injection

  9. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Change from baseline to 6weeks after injection

  10. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 6weeks after injection

  11. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Change from baseline to 3Months after injection

  12. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for NPRS from baseline and 3Months after injection

  13. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Change from baseline to 6Months after injection

  14. Change in patient reported outcome measures, Numeric Pain Rating Scale

    To determine change in patient reported outcome measure, Numeric Pain Rating Scale (NPRS). A decrease in score indicates improvement.

    Measured: Change from baseline to 1year after injection

  15. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score

    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

    Measured: Change from baseline to 1week after injection

  16. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score

    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

    Measured: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for KOOS from baseline and 1week after injection

  17. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score

    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

    Measured: Change from baseline to 6weeks after injection

  18. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score

    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

    Measured: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for KOOS from baseline and 6weeks after injection

  19. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score

    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

    Measured: Change from baseline to 3Months after injection

  20. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score

    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

    Measured: Difference between groups (Wharton's Jelly, Hyaluronic Acid and Saline) in changes score for KOOS from baseline and 3Months after injection

  21. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score

    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

    Measured: Change from baseline to 6Months after injection

  22. Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score

    To determine change in patient reported outcome measure, Knee Injury and Osteoarthritis Outcome Score (KOOS). An increase in score indicates improvement.

    Measured: Change from baseline to 1Year after injection

  23. Cartilage Formation

    To assess cartilage formation via MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue). An increase in score indicates improvement.

    Measured: Change from baseline to 1year after injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jan 2021
  2. Study start1 Jan 2023 (estimated)
  3. Primary completion1 Jun 2026 (estimated)
  4. Study completion1 Jun 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
168 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04711304
Sponsor's protocol ID
BIOINT - 2020WJ/OA
Status last verified
Jul 2022
First submitted
13 Jan 2021
Last updated
21 Jul 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gupta A, Maffulli N, Rodriguez HC, Carson EW, Bascharon RA, Delfino K, Levy HJ, El-Amin SF 3rd. Safety and efficacy of umbilical cord-derived Wharton's jelly compared to hyaluronic acid and saline for knee osteoarthritis: study protocol for a randomized, controlled, single-blind, multi-center trial. J Orthop Surg Res. 2021 May 31;16(1):352. doi: 10.1186/s13018-021-02475-6.

    PubMed 34059080

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Umbilical Cord-derived Wharton's Jelly, Hyaluronic acid and Saline in people with Osteoarthritis, Knee, run by BioIntegrate.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 21 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Saadiq F. El-Amin III, MD, PhD (678-257-7078, dr.saadiqelamin@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse or severe adverse events associated with intraarticular administration of umbilical cord-derived Wharton's Jelly (time frame: Immediately after injection). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04711304, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2022.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in