Osteoarthritis, KneePhase 2/3NCT05076526
PRP-HA Versus HA in Knee Osteoarthritis
A Phase 2/3 study testing Hyaluronic acid (Synolis VA) and Cellular Matrix platelet-rich-plasma with hyaluronic acid (CM PRP-HA) in people with Osteoarthritis, Knee, run by Singapore General Hospital.
Trial summary
Osteoarthritis (OA) is a prevalent chronic condition which most commonly affects the knee. The pathogenesis of OA involves initial mechanical stress resulting in cartilage lesions, leading to inflammatory processes causing joint degradation. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- Hyaluronic acid (Synolis VA) and Cellular Matrix platelet-rich-plasma with hyaluronic acid (CM PRP-HA)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- No sites listed yet
- Study dates
- Nov 2021to Nov 2022
- Phase
- Phase 2/3
- 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 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients of age 30 years and above
- Radiographical diagnosis of knee OA - ie narrowing of joint space, presence of osteophytes, possible sclerosis and subchondral cysts
- History of chronic pain in knee or knee swelling for at least 3 months
- Ability of patients to provide informed consent
Who cannot join
- Concurrent complementary and alternative medicine (CAM) treatments e.g. acupuncture
- Inflammatory diseases / infection / fracture / trauma
- Malignancies
- Pregnant or lactating females
- Consistent use of NSAIDs within 48 hours of procedure
- Corticosteroid injection at treatment site within 1 month
Show all 9Show fewer
- Systemic use of corticosteroids within 2 weeks
- Tobacco use
- (For patients receiving PRP-HA injection only): Hemoglobin <10 g/dL and platelets <150,000/mm3
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Randomized Controlled Trial Comparing Cellular Matrix Combination of Platelet Rich Plasma With Hyaluronic Acid (CM-PRP-HA) Versus Hyaluronic Acid in Knee Osteoarthritis
Osteoarthritis (OA) is a prevalent chronic condition which most commonly affects the knee. The pathogenesis of OA involves initial mechanical stress resulting in cartilage lesions, leading to inflammatory processes causing joint degradation. Numerous pharmacological and non-pharmacological therapies have been employed, including hyaluronic acid (HA) supplementations to alleviate the joint damage from mechanical load by acting as a shock absorber which provides lubrication, and intra-articular corticosteroid injections to reduce inflammation. However, HA is unable to facilitate cartilage regeneration and corticosteroids has numerous undesirable side effects which render them unsustainable treatment options.
Recently, many studies worldwide have demonstrated that platelet-rich-plasma (PRP) stimulates cartilage repair by actively secreting growth factors which activate cell proliferation and differentiation thereby promoting tissue regeneration. However, there has been varying results across various RCTs due to the heterogeneity of studies, with inconclusive recommendations on the treatment regimen for PRP-HA. Currently, PRP treatment is also not formally recognized as a treatment modality for knee OA in many countries, including Singapore.
This randomised controlled trial aims to compare the efficacy of Cellular Matrix (CM) PRP-HA versus HA (Synolis VA) intra-articular injections in knee OA through quantifying the improvement in long-term treatment outcomes such as pain, stiffness, and functional impairment, potentially improving the quality of life for many patients with knee OA.
Read the detailed description
In vitro experimentations have also established the efficacy of PRP, where chondrocytes stimulated with PRP has shown to increase proteoglycan and collagen synthesis which bears similar biochemical qualities to that of hyaline cartilage. PRP has also shown to provide more critical growth factors (including PDGF, TGF-beta, IGF, EGF, VEGF, FGF) than conventional culture media, increasing the synthesis of major cellular proteins and collagen in the extracellular component of intervertebral disc cells, potentially enhancing the functional properties of joint cartilages.
Presently, cellular matrix (CM) remains as the only device which allows for the combination of PRP and HA to be delivered to patients within a single intra-articular injection. However, there are insufficient large-scale studies to reliably evaluate the efficacy of PRP-HA on knee OA and formulate a universal recommendation on its treatment regimen. There are also no RCTs conducted on our local population to explore the effects of CM-PRP-HA on knee OA.
- Conditions
- Osteoarthritis, Knee
- Being tested
- Hyaluronic acid (Synolis VA), Cellular Matrix platelet-rich-plasma with hyaluronic acid (CM PRP-HA)
- Keywords
- Platelet-rich plasma, Hyaluronic acid
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyaluronic acid (Synolis VA)Biological
Synolis VA harbours the following characteristics:
- NaHA (Sodium hyaluronate): 20mg/mL, biofermantative and pharmaceutical grade origin.
- Sorbitol: 40mg/mL
- Molecular weight of 2MDa, sterilized in moist heat
Cellular Matrix platelet-rich-plasma with hyaluronic acid (CM PRP-HA)Biological
The CM-PRP-HA tube is under vacuum containing the following:
- 2mL of hyaluronic acid gel in phosphate buffer (Sodium chloride, Dipotassium hydrogenphosphate, Potassium dihydrogenphosphate, Potassium chloride and water for injection). Not crosslinked Hyaluronic Acid (40mg per tube) is obtained from fermentation
- 3g of inert cell-selector gel
- 0.6mL of anticoagulant (sodium citrate 4%)
| Study group | Role | What they receive |
|---|---|---|
| HA | Active comparator | Patients will receive 2 intra-articular injections of 2mL Synolis VA (20 mg/mL HA and 40 mg/mL sorbitol), with an interval of 1 month between both injections. Receives: Biological: Hyaluronic acid (Synolis VA) |
| PRP-HA | Experimental | Patients will receive 2 intra-articular injections of 5mL CM-PRP-HA combination (3mL of autologous PRP, 2mL of 16mg/mL HA), with an interval of 1 month between both injections. Receives: Biological: Cellular Matrix platelet-rich-plasma with hyaluronic acid (CM PRP-HA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score
WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes
Measured: Baseline
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline at 1 month
WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes
Measured: 1 month after last injection
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline at 3 months
WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes
Measured: 3 months after last injection
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline at 6 months
WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes
Measured: 6 months after last injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2021
- Study startNov 2021 (estimated)
- Primary completionNov 2022 (estimated)
- Study completionNov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- More trials run by Singapore General HospitalThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a single-blinded randomised controlled trial.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 132 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kenon Chua Ser, Singapore General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05076526
- Sponsor's protocol ID
- In progress
- Status last verified
- Oct 2021
- First submitted
- 1 Jul 2021
- Last updated
- 13 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Aggregate data will be made available
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial Comparing Cellular Matrix Combination of Platelet Rich Plasma With Hyaluronic Acid (CM-PRP-HA) Versus Hyaluronic Acid in Knee Osteoarthritis
- ClinicalTrials.gov ID
- NCT05076526
- Acronym / sponsor ID
- In progress
- Conditions
- Osteoarthritis, Knee
- Keywords
- Platelet-rich plasma, Hyaluronic acid
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 132 participants (estimated)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Study start
- Nov 2021 (estimated)
- Primary completion
- Nov 2022 (estimated)
- Study completion
- Nov 2022 (estimated)
- First posted
- 13 Oct 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.
Osteoarthritis (OA) is a prevalent chronic condition which most commonly affects the knee. The pathogenesis of OA involves initial mechanical stress resulting in cartilage lesions, leading to inflammatory processes causing joint degradation. Numerous pharmacological and non-pharmacological therapies have been employed, including hyaluronic acid (HA) supplementations to alleviate the joint damage from mechanical load by acting as a shock absorber which provides lubrication, and intra-articular corticosteroid injections to reduce inflammation. However, HA is unable to facilitate cartilage regeneration and corticosteroids has numerous undesirable side effects which render them unsustainable treatment options.
Recently, many studies worldwide have demonstrated that platelet-rich-plasma (PRP) stimulates cartilage repair by actively secreting growth factors which activate cell proliferation and differentiation thereby promoting tissue regeneration. However, there has been varying results across various RCTs due to the heterogeneity of studies, with inconclusive recommendations on the treatment regimen for PRP-HA. Currently, PRP treatment is also not formally recognized as a treatment modality for knee OA in many countries, including Singapore.
This randomised controlled trial aims to compare the efficacy of Cellular Matrix (CM) PRP-HA versus HA (Synolis VA) intra-articular injections in knee OA through quantifying the improvement in long-term treatment outcomes such as pain, stiffness, and functional impairment, potentially improving the quality of life for many patients with knee OA.
Detailed description
In vitro experimentations have also established the efficacy of PRP, where chondrocytes stimulated with PRP has shown to increase proteoglycan and collagen synthesis which bears similar biochemical qualities to that of hyaline cartilage. PRP has also shown to provide more critical growth factors (including PDGF, TGF-beta, IGF, EGF, VEGF, FGF) than conventional culture media, increasing the synthesis of major cellular proteins and collagen in the extracellular component of intervertebral disc cells, potentially enhancing the functional properties of joint cartilages.
Presently, cellular matrix (CM) remains as the only device which allows for the combination of PRP and HA to be delivered to patients within a single intra-articular injection. However, there are insufficient large-scale studies to reliably evaluate the efficacy of PRP-HA on knee OA and formulate a universal recommendation on its treatment regimen. There are also no RCTs conducted on our local population to explore the effects of CM-PRP-HA on knee OA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- This is a single-blinded randomised controlled trial.
| Arm | Type | Receives |
|---|---|---|
| HA | Active comparator | Biological: Hyaluronic acid (Synolis VA)Patients will receive 2 intra-articular injections of 2mL Synolis VA (20 mg/mL HA and 40 mg/mL sorbitol), with an interval of 1 month between both injections. |
| PRP-HA | Experimental | Biological: Cellular Matrix platelet-rich-plasma with hyaluronic acid (CM PRP-HA)Patients will receive 2 intra-articular injections of 5mL CM-PRP-HA combination (3mL of autologous PRP, 2mL of 16mg/mL HA), with an interval of 1 month between both injections. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients of age 30 years and above
- Radiographical diagnosis of knee OA - ie narrowing of joint space, presence of osteophytes, possible sclerosis and subchondral cysts
- History of chronic pain in knee or knee swelling for at least 3 months
- Ability of patients to provide informed consent
Key exclusion criteria (9 listed)
- Concurrent complementary and alternative medicine (CAM) treatments e.g. acupuncture
- Inflammatory diseases / infection / fracture / trauma
- Malignancies
- Pregnant or lactating females
- Consistent use of NSAIDs within 48 hours of procedure
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 |
|---|---|---|
| Hyaluronic acid (Synolis VA)Synolis VA harbours the following characteristics: * NaHA (Sodium hyaluronate): 20mg/mL, biofermantative and pharmaceutical grade origin. * Sorbitol: 40mg/mL * Molecular weight of 2MDa, sterilized in moist heat | Biological | HA |
| Cellular Matrix platelet-rich-plasma with hyaluronic acid (CM PRP-HA)The CM-PRP-HA tube is under vacuum containing the following: * 2mL of hyaluronic acid gel in phosphate buffer (Sodium chloride, Dipotassium hydrogenphosphate, Potassium dihydrogenphosphate, Potassium chloride and water for injection). Not crosslinked Hyaluronic Acid (40mg per tube) is obtained from fermentation * 3g of inert cell-selector gel * 0.6mL of anticoagulant (sodium citrate 4%) | Biological | PRP-HA |
Primary outcome
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score
Time frame: Baseline
WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline at 1 month
Time frame: 1 month after last injection
WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline at 3 months
Time frame: 3 months after last injection
WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline at 6 months
Time frame: 6 months after last injection
WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2021.
- Individual participant dataSharing planned: No. Aggregate data will be made available
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Hyaluronic acid (Synolis VA) and Cellular Matrix platelet-rich-plasma with hyaluronic acid (CM PRP-HA) in people with Osteoarthritis, Knee, run by Singapore General Hospital.
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 4 inclusion and 9 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 13 Oct 2021. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Kenon Chua, MBBS, MRCSEd, FRCSEd (+65 6222 3322, kenonchua@icloud.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Oct 2021.