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.
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
- Type of treatment
- Injection or infusion, Medical device
- 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.
Ashim Gupta, PhD, MBA contact
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.
- Conditions
- Osteoarthritis, Knee
- 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 group | Role | What they receive |
|---|---|---|
| Wharton's Jelly | Experimental | Intraarticular injection of Wharton's Jelly Receives: Biological: Umbilical Cord-derived Wharton's Jelly |
| Hyaluronic Acid | Active comparator | Intraarticular injection of Hyaluronic Acid Receives: Device: Hyaluronic acid |
| Saline | Placebo comparator | Intraarticular injection of Saline Receives: Other: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
- First posted15 Jan 2021
- Study start1 Jan 2023 (estimated)
- Primary completion1 Jun 2026 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- BioIntegrate
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Saadiq F. El-Amin III, MD, PhD, Principal investigator, El-Amin Orthopaedic & Sports Medicine InstituteAshim Gupta, PhD, MBA, Study director, BioIntegrate
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
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04711304
- Acronym / sponsor ID
- BIOINT - 2020WJ/OA
- Conditions
- Osteoarthritis, Knee
- Keywords
- Knee Osteoarthritis, Umbilical Cord, Wharton's Jelly
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 168 participants (estimated)
- Lead sponsor
- BioIntegrateIndustry (pharma, biotech, devices)
- Study start
- 1 Jan 2023 (estimated)
- Primary completion
- 1 Jun 2026 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 15 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Wharton's Jelly | Experimental | Biological: Umbilical Cord-derived Wharton's JellyIntraarticular injection of Wharton's Jelly |
| Hyaluronic Acid | Active comparator | Device: Hyaluronic acidIntraarticular injection of Hyaluronic Acid |
| Saline | Placebo comparator | Other: SalineIntraarticular injection of Saline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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).
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Umbilical Cord-derived Wharton's JellyIntraarticular injection | Biological | Wharton's Jelly |
| Hyaluronic acidIntraarticular injection | Device | Hyaluronic Acid |
| SalineIntraarticular injection | Other | Saline |
Primary outcome
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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)
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)
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)
23 secondary outcomes
Change in patient reported outcome measures, Numeric Pain Rating Scale
Time frame: Change from baseline to immediately after injection
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
Change in patient reported outcome measures, Numeric Pain Rating Scale
Time frame: Change from baseline to 24hours after injection
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
Change in patient reported outcome measures, Numeric Pain Rating Scale
Time frame: Change from baseline to 48hours after injection
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
Change in patient reported outcome measures, Numeric Pain Rating Scale
Time frame: Change from baseline to 1week after injection
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
Change in patient reported outcome measures, Numeric Pain Rating Scale
Time frame: Change from baseline to 6weeks after injection
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
Change in patient reported outcome measures, Numeric Pain Rating Scale
Time frame: Change from baseline to 3Months after injection
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
Change in patient reported outcome measures, Numeric Pain Rating Scale
Time frame: Change from baseline to 6Months after injection
Change in patient reported outcome measures, Numeric Pain Rating Scale
Time frame: Change from baseline to 1year after injection
Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
Time frame: Change from baseline to 1week after injection
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
Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
Time frame: Change from baseline to 6weeks after injection
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
Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
Time frame: Change from baseline to 3Months after injection
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
Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
Time frame: Change from baseline to 6Months after injection
Change in patient reported outcome measures, Knee Injury and Osteoarthritis Outcome Score
Time frame: Change from baseline to 1Year after injection
Cartilage Formation
Time frame: Change from baseline to 1year after injection
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2022.
- Derived from this study: PubMed 34059080Gupta 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashim Gupta, PhD, MBA contact
Saadiq F. El-Amin III, MD, PhD principal investigator
El-Amin Orthopaedic & Sports Medicine Institute
Ashim Gupta, PhD, MBA study director
BioIntegrate
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.