Back to resultsCellular Matrix Device for the Treatment of Mild to Moderate Knee Osteoarthritis
Primary Purpose
Knee Osteoarthritis
Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Cellular Matrix / A-CP HA Kit
Synvisc-One
Sponsored by
About this trial
This is an interventional treatment trial for Knee Osteoarthritis
Eligibility Criteria
Inclusion Criteria:
- femorotibial knee osteoarthritis defined according to the American College of Rheumatology (ACR) criteria
- Symptomatic knee osteoarthritis of a unilateral knee, characterized by pain at walking (WOMAC A1 score assessed over the previous 24 hours on a 100-mm Visual Analog Scale (VAS): 50 ≤ WOMAC A1 ≤ 90) or reduced joint function (total WOMAC C score assessed or over the previous 24 hours on a 100-mm VAS: 50 ≤ WOMAC A1 ≤ 90)
- Bilateral knee osteoarthritis is allowed, provided the contralateral knee is characterized by a maximum pain of 30 on a 0 to 100 mm scale and doesn't require systemic analgesic treatment, with the exception of paracetamol up to the maximum dose of 4 g per day
- Radiographic femorotibial knee osteoarthritis (radiograph not older than 3 months) Kellgren & Lawrence grades of II-III
- Outpatient capable of walking 50 meters without assistance
- Signature of the informed consent form
- Capable of understanding the study's imperatives, as well as written instructions
- Capable of filling-out evaluation questionnaires
Exclusion Criteria:
- Radiographic femoro-tibial knee osteoarthritis Kellgren & Lawrence grades of I or IV
- Bilateral knee osteoarthritis, characterized by pain greater than 30 of both knees evaluated on a 0 to 100-mm scale and requiring systemic analgesic treatment or paracetamol greater than 4g/ day
- Viscosupplementation in the past 3 months
- Corticosteroid injection in the past 3 months
- PRP or PRP/HA injection in the past 12 months
- Any surgery of the knee planned during the next 6 months
- Systematic use of corticosteroids (except those that are inhaled) or level III analgesics in the past 3 months and NSAID (non-steroidal anti-inflammatory drugs) during the past month
- Treatment with slow-acting anti-rheumatic drugs (diacerhein, soybean or avocado unsaponifiables, chondroitin sulfate, glucosamine) started in the past 6 months
- History of allergy to hyaluronic acid
- Auto-immune disease (rheumatoid arthritis, lupus)
- Surgery of the affected knee in the past 3 months
- Infection of the affected knee in the past 6 months
- Rheumatologic disorder other than arthritis
- Clinical evidence of local inflammation such as redness or heat of the joint
- Hereditary or acquired hematologic or clotting disorders, such as drepanocytosis, platelet dysfunction, thrombocytopenia (<150'000 platelets/mm3), etc.
- Anemia (Hemoglobin < 10g/dl)
- Anticoagulant treatment (patients under antiaggregant treatment can take part to this study as long as their clotting time (CT) is within the reference value)
- Acute infection
- Malignant disease (especially bone and hematological
- serious disorders (cardiovascular pathology, active gastroduodenal ulcer, digestive hemorrhage)
- Patient with renal impairment (creatinine clearance below 45 ml / min)
- Patient with liver failure, pending or who have recently received a liver transplant
- Pregnancy or breastfeeding or planning pregnancy during the course of the study
- Immunosuppression
- Insulin-dependent diabetic patient
- Participation ongoing or in the past 3 months in another clinical study
- Participation to another osteoarthritis clinical study during the past year
- Patient unable to submit to the constraints of the protocol, including patient whose mental condition does not allow him to understand the nature, objectives and possible consequences of the study
- Any other reason which, in the opinion of the investigator, may interfere with the proper conduct of the study
Sites / Locations
- Clinique Médipôle garonneRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Cellular Matrix / A-CP HA Kit
Synvisc-One
Arm Description
One intra-articular injection of a combination of PRP and non-crosslinked HA
One intra-articular injection of a crosslinked HA
Outcomes
Primary Outcome Measures
Change from Baseline pain on walking (Western Ontario & McMaster Universities [WOMAC] A1 of the WOMAC questionaire) at 6 months
For each group, pain on walking will be evaluated using a 100-mm Visual Analog Scale (VAS), where 0= no pain and 100 = extreme pain
Secondary Outcome Measures
Change from Baseline pain on walking at 1 and 3 months
For each group, pain on walking will be evaluated using a 100-mm Visual Analog Scale (VAS), where 0= no pain and 100 = extreme pain
Change from Baseline overall knee osteoarthritis symptoms at 1, 3 and 6 Months
For each group, overall knee osteoarthritis will be evaluated using the total WOMAC questionnaire; each item of this questionnaire will be scored using a 100-mm VAS at baseline, Month 1, Month 3, and Month 6. The total WOMAC score will be reported as a summed score of all items of the questionnaire, with 0 is the minimum and 2400 is the maximum.
Change from Baseline pain at 1, 3 and 6 Months
For each group, pain will be evaluated using the WOMAC A subscale; each item of this subscale will be scored using a 100-mm VAS at baseline, Month 1, Month 3, and Month 6. The total WOMAC A score will be reported as a summed score of all items of this subscale, where 0 = is the minimum (no pain) and 500 is the maximum (extreme pain).
Change from Baseline stiffness at 1, 3 and 6 Months
For each group, stiffness will be evaluated using the WOMAC B subscale; each item of this subscale will be scored using a 100-mm VAS at baseline, Month 1, Month 3, and Month 6. The total WOMAC B score will be reported as a summed score of all items of this subscale, where 0 = is the minimum (no stiffness) and 200 is the maximum (extreme stiffness).
Change from Baseline physical function at 1, 3 and 6 Months
For each group, physical function will be evaluated using the WOMAC C subscale; each item of this subscale will be scored using a 100-mm VAS at baseline, Month 1, Month 3, and Month 6. The total WOMAC C score will be reported as a summed score of all items of this subscale, where 0 = is the minimum (no difficulty to perform activities) and 1700 is the maximum (extreme difficulty to perform activities).
Change from Baseline quality of life at all time points
Quality of life will be assessed using the 36-Item Short Form (SF-36) survey that will be given to patients at each visit throughout the study.
Patient Global Assessment of the treatment received
Patient Global Assessment will be performed using a 5-point numeric scale at 1, 3 and 6 Months, with 1 = completely dissatisfied, 2= dissatisfied, 3 = no change, 4=satisfied , 5= completely satisfied
Clinician Global Assessment of the treatment received
Patient Global Assessment will be performed using a 5-point numeric scale at 1, 3 and 6 Months, 1 = completely dissatisfied, 2= dissatisfied, 3 = no change, 4=satisfied , 5= completely satisfied
Percentage of OMERACT-OARSI (Outcome Measure in Rheumatology - Osteoarthitis Research Society International) responders at 1, 3 and 6 Months
Percentage of patients requiring an injection of the combination of PRP/HA prepared with Cellular Matrix / A-CP HA at 6 Months
Number of local and systemic side effects throughout the study period
Cartilage structure
The cartilage structure will be evaluated on the basis of Magnetic Resonance Imaging (MRI) assays at baseline (before receiving the treatment) and 6 months. Differences on the T1 relaxation time parameter will be evaluated at different time points.
Rescue treatment consumption at 1, 3 and 6 Months
Consumption of authorized medication to relieve pain, according to the patient's diary
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03328728
Brief Title
Cellular Matrix Device for the Treatment of Mild to Moderate Knee Osteoarthritis
Official Title
A Prospective, Multicenter, Randomized,Controlled Study to Compare the Safety and Performance of Cellular Matrix Device (Combination of Autologous Platelet-rich Plasma and Non-crosslinked Hyaluronic Acid) to Those of Synvisc-One (Crosslinked Hyaluronic Acid) for the Treatment of Mild to Moderate Knee Osteoarthritis
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 18, 2017 (Actual)
Primary Completion Date
March 31, 2021 (Anticipated)
Study Completion Date
March 31, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regen Lab SA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a non-inferiority study on 190 patients to evaluate whether a treatment based on the combination of autologous platelet-rich plasma and hyaluronic acid obtained with Cellular Matrix represents a therapeutic advantage to relieve symptoms associated with a mild to moderate knee osteoarthritis (particularly pain on walking) compared to hyaluronic acid only (Synvisc®-One).
Detailed Description
Platelet-rich plasma (PRP) is an autologous product prepared from the patient's own blood, representing a powerful source of platelet-derived growth factors, particularly useful in the field of regenerative medicine. The active and sequential secretion of these growth factors induces different cell signaling cascades that activate angiogenesis, cell proliferation, cell differentiation, eventually leading to new matrix synthesis and tissue regeneration.
The potential benefits from the use of PRP for the treatment of cartilage defects rely on a number of studies conducted in validated animal models or in vitro, demonstrating the ability of PRP to stimulate collagen production and proteoglycans synthesis, as well as the proliferation and differentiation of mesenchymal stem cells into chondrocytes. Additionally, an increasing number of clinical studies shows an improvement of symptoms, most especially pain, without any occurrence of serious adverse events.
Hyaluronic acid (HA), as one of the major components of the synovial fluid surrounding the cartilage, assumes an important role in the viscoelastic properties of the articular cartilage, conferring its shock absorbing and lubricating functions.
It was demonstrated that rheological properties of synovial fluid decrease with aging and in patients suffering from osteoarthritis. Nowadays, intra-articular injections of hyaluronic acid represent a well recommended therapeutic option to relieve osteoarthritic symptoms, conferring a mechanical action on joints structures, thus leading to reduced pain and improved joint function Based on these data, it seems reasonable to hypothesize that a combination of both PRP and hyaluronic acid could provide greater benefits compared to the administration of each product alone, as their effects on osteoarthritis improvement are based on different mechanisms of action. In fact, on one side PRP promotes cartilage regeneration, while on the other side the HA acts as 3-dimensional support mesh for PRP, providing optimal release of platelets growth factors, strengthening and extending in time the activity of PRP.
Cellular Matrix/A-CP HA Kit is a medical device manufactured by the Swiss company Regen Lab SA. Cellular Matrix/A-CP HA Kit allows to prepare autologous PRP combined with a non-crosslinked hyaluronic acid in a safe, rapid manner and in a single step. The PRP/HA combination is intended to be injected intra-articularly, in order to relieve osteoarthritic symptoms and to improve joint mobility and function. Therefore, the PRP/HA combination might represent a novel therapeutic option for patient suffering from knee osteoarthritis.
This study will evaluate the effects of a single intra-articular injection of a PRP/HA combination prepared with Cellular Matrix/A-CP HA Kit, compared to those of a intra-articular single injection of a well-recognized hyaluronic acid treatment (Synvisc®-One), to relieve symptoms associated with mild to moderate knee osteoarthritis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Knee Osteoarthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
190 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cellular Matrix / A-CP HA Kit
Arm Type
Experimental
Arm Description
One intra-articular injection of a combination of PRP and non-crosslinked HA
Arm Title
Synvisc-One
Arm Type
Active Comparator
Arm Description
One intra-articular injection of a crosslinked HA
Intervention Type
Device
Intervention Name(s)
Cellular Matrix / A-CP HA Kit
Intervention Description
Treatment with a single intra-articular injection in the knee of Cellular Matrix / A-CP HA Kit; Cellular Matrix / A-CP HA Kit is designed for the safe, rapid and extemporaneous preparation of a cellular matrix of autologous PRP combined with HA. The Cellular Matrix / A-CP HA Kit is a single-use medical device including hematology tubes (A-CP HA tube), designed for blood collection and PRP/HA preparation after 5 min centrifugation. This tube contains a non-crosslinked hyaluronic acid (MW 1550 kDa) solution, a gel acting as a cell separator, and a sodium citrate acting as an anticoagulant. During centrifugation, the separator gel moves to form a barrier that separates red blood cells from other blood components. The HA, which migrates to the top of the gradient during centrifugation, can be mixed with PRP in order to give rise to a ready-to-use PRP/HA preparation.
Intervention Type
Device
Intervention Name(s)
Synvisc-One
Intervention Description
Treatment with a single intra-articular injection in the knee of Synvisc-One; Synvisc-One (hylan G-F 20) is a sterile, nonpyrogenic, elastoviscous fluid containing hylans. Hylans are derivatives of hyaluronans (sodium salt of hyaluronic acid). Hylan A has an average molecular weight of 6,000,000 daltons and hylan B is a hydrated gel. Hylan G-F 20 contains hylan A and hylan B (8.0 mg per ml) in buffered physiological sodium chloride solution.
Primary Outcome Measure Information:
Title
Change from Baseline pain on walking (Western Ontario & McMaster Universities [WOMAC] A1 of the WOMAC questionaire) at 6 months
Description
For each group, pain on walking will be evaluated using a 100-mm Visual Analog Scale (VAS), where 0= no pain and 100 = extreme pain
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change from Baseline pain on walking at 1 and 3 months
Description
For each group, pain on walking will be evaluated using a 100-mm Visual Analog Scale (VAS), where 0= no pain and 100 = extreme pain
Time Frame
1 and 3 months
Title
Change from Baseline overall knee osteoarthritis symptoms at 1, 3 and 6 Months
Description
For each group, overall knee osteoarthritis will be evaluated using the total WOMAC questionnaire; each item of this questionnaire will be scored using a 100-mm VAS at baseline, Month 1, Month 3, and Month 6. The total WOMAC score will be reported as a summed score of all items of the questionnaire, with 0 is the minimum and 2400 is the maximum.
Time Frame
1, 3 and 6 months
Title
Change from Baseline pain at 1, 3 and 6 Months
Description
For each group, pain will be evaluated using the WOMAC A subscale; each item of this subscale will be scored using a 100-mm VAS at baseline, Month 1, Month 3, and Month 6. The total WOMAC A score will be reported as a summed score of all items of this subscale, where 0 = is the minimum (no pain) and 500 is the maximum (extreme pain).
Time Frame
1, 3 and 6 months
Title
Change from Baseline stiffness at 1, 3 and 6 Months
Description
For each group, stiffness will be evaluated using the WOMAC B subscale; each item of this subscale will be scored using a 100-mm VAS at baseline, Month 1, Month 3, and Month 6. The total WOMAC B score will be reported as a summed score of all items of this subscale, where 0 = is the minimum (no stiffness) and 200 is the maximum (extreme stiffness).
Time Frame
1, 3 and 6 months
Title
Change from Baseline physical function at 1, 3 and 6 Months
Description
For each group, physical function will be evaluated using the WOMAC C subscale; each item of this subscale will be scored using a 100-mm VAS at baseline, Month 1, Month 3, and Month 6. The total WOMAC C score will be reported as a summed score of all items of this subscale, where 0 = is the minimum (no difficulty to perform activities) and 1700 is the maximum (extreme difficulty to perform activities).
Time Frame
1, 3 and 6 months
Title
Change from Baseline quality of life at all time points
Description
Quality of life will be assessed using the 36-Item Short Form (SF-36) survey that will be given to patients at each visit throughout the study.
Time Frame
1, 3 and 6 months
Title
Patient Global Assessment of the treatment received
Description
Patient Global Assessment will be performed using a 5-point numeric scale at 1, 3 and 6 Months, with 1 = completely dissatisfied, 2= dissatisfied, 3 = no change, 4=satisfied , 5= completely satisfied
Time Frame
1, 3 and 6 months
Title
Clinician Global Assessment of the treatment received
Description
Patient Global Assessment will be performed using a 5-point numeric scale at 1, 3 and 6 Months, 1 = completely dissatisfied, 2= dissatisfied, 3 = no change, 4=satisfied , 5= completely satisfied
Time Frame
1, 3 and 6 months
Title
Percentage of OMERACT-OARSI (Outcome Measure in Rheumatology - Osteoarthitis Research Society International) responders at 1, 3 and 6 Months
Time Frame
1, 3 and 6 months
Title
Percentage of patients requiring an injection of the combination of PRP/HA prepared with Cellular Matrix / A-CP HA at 6 Months
Time Frame
6 months
Title
Number of local and systemic side effects throughout the study period
Time Frame
6 months
Title
Cartilage structure
Description
The cartilage structure will be evaluated on the basis of Magnetic Resonance Imaging (MRI) assays at baseline (before receiving the treatment) and 6 months. Differences on the T1 relaxation time parameter will be evaluated at different time points.
Time Frame
6 months
Title
Rescue treatment consumption at 1, 3 and 6 Months
Description
Consumption of authorized medication to relieve pain, according to the patient's diary
Time Frame
1, 3 and 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
femorotibial knee osteoarthritis defined according to the American College of Rheumatology (ACR) criteria
Symptomatic knee osteoarthritis of a unilateral knee, characterized by pain at walking (WOMAC A1 score assessed over the previous 24 hours on a 100-mm Visual Analog Scale (VAS): 50 ≤ WOMAC A1 ≤ 90) or reduced joint function (total WOMAC C score assessed or over the previous 24 hours on a 100-mm VAS: 50 ≤ WOMAC A1 ≤ 90)
Bilateral knee osteoarthritis is allowed, provided the contralateral knee is characterized by a maximum pain of 30 on a 0 to 100 mm scale and doesn't require systemic analgesic treatment, with the exception of paracetamol up to the maximum dose of 4 g per day
Radiographic femorotibial knee osteoarthritis (radiograph not older than 3 months) Kellgren & Lawrence grades of II-III
Outpatient capable of walking 50 meters without assistance
Signature of the informed consent form
Capable of understanding the study's imperatives, as well as written instructions
Capable of filling-out evaluation questionnaires
Exclusion Criteria:
Radiographic femoro-tibial knee osteoarthritis Kellgren & Lawrence grades of I or IV
Bilateral knee osteoarthritis, characterized by pain greater than 30 of both knees evaluated on a 0 to 100-mm scale and requiring systemic analgesic treatment or paracetamol greater than 4g/ day
Viscosupplementation in the past 3 months
Corticosteroid injection in the past 3 months
PRP or PRP/HA injection in the past 12 months
Any surgery of the knee planned during the next 6 months
Systematic use of corticosteroids (except those that are inhaled) or level III analgesics in the past 3 months and NSAID (non-steroidal anti-inflammatory drugs) during the past month
Treatment with slow-acting anti-rheumatic drugs (diacerhein, soybean or avocado unsaponifiables, chondroitin sulfate, glucosamine) started in the past 6 months
History of allergy to hyaluronic acid
Auto-immune disease (rheumatoid arthritis, lupus)
Surgery of the affected knee in the past 3 months
Infection of the affected knee in the past 6 months
Rheumatologic disorder other than arthritis
Clinical evidence of local inflammation such as redness or heat of the joint
Hereditary or acquired hematologic or clotting disorders, such as drepanocytosis, platelet dysfunction, thrombocytopenia (<150'000 platelets/mm3), etc.
Anemia (Hemoglobin < 10g/dl)
Anticoagulant treatment (patients under antiaggregant treatment can take part to this study as long as their clotting time (CT) is within the reference value)
Acute infection
Malignant disease (especially bone and hematological
serious disorders (cardiovascular pathology, active gastroduodenal ulcer, digestive hemorrhage)
Patient with renal impairment (creatinine clearance below 45 ml / min)
Patient with liver failure, pending or who have recently received a liver transplant
Pregnancy or breastfeeding or planning pregnancy during the course of the study
Immunosuppression
Insulin-dependent diabetic patient
Participation ongoing or in the past 3 months in another clinical study
Participation to another osteoarthritis clinical study during the past year
Patient unable to submit to the constraints of the protocol, including patient whose mental condition does not allow him to understand the nature, objectives and possible consequences of the study
Any other reason which, in the opinion of the investigator, may interfere with the proper conduct of the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Valérie de Fourmestraux, PhD
Phone
+41(0)218640110
Ext
118
Email
vdefourmestraux@regenlab.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe Adam, MD
Organizational Affiliation
Clinique Médipôle Garonne
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinique Médipôle garonne
City
Toulouse
State/Province
Haute-Garonne
ZIP/Postal Code
31036
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe Adam, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Cellular Matrix Device for the Treatment of Mild to Moderate Knee Osteoarthritis
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