Arthritis of Knee, Knee Osteoarthritis, Osteoarthritis, Knee
Conditions
Keywords
Knee degenerative disease, osteoarthritis, gonarthrosis, stem cell, cellular therapy, regenerative therapy, Mesenchymal stem cells, Bone marrow, musculoskeletal Diseases, Mesenchymal Stromal Cells (allogenic)
Brief summary
In this study we want to evaluate the clinical use of allogenic mesenchymal stem cells (MSC), obtained from bone marrow of healthy donors, for treatment of knee osteoarthritis. The trial is based in our own previous results with autologous MSC (ongoing NCT01183728 trial). We propose here a multicenter, phase I-II clinical trial, prospective, randomized, blinded, and controlled for the treatment of osteoarthritis (degrees II and III and IV). The assay consists of two arms with 15 patients each one. Patients in the experimental arm will be given an intra-articular transplantation of allogenic MSC, expanded Ex Vivo with our GMP-compliant procedure (MSV, PEI No. 10-134, authorized by the Competent Authority; same as in NCT01183728). In the control arm a standard treatment with intra-articular injection of hyaluronic acid shall be given. We shall follow the evolution of pain, disability, quality of life and quantitative changes in structure and composition of cartilage determined by T2-weighted MRI relaxation (Cartigram) for one year.
Interventions
OTHERAllogenic mesenchymal stromal cells injection
Mesenchymal stem cells prepared from bone marrow of healthy donors and expanded for 3-4 weeks according to our procedure described in PEI Num. 10-134, authorized by the Spanish Medicine Agency
DRUGHyaluronic Acid
Intra-articular injection of 60 mg of hyaluronic acid (Durolane) in a single injection (3 ml)
Sponsors
University of Valladolid
Sanidad de Castilla y León
Centro Medico Teknon
Red de Terapia Celular
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Knee osteoarthritis grade II, III and IV of Kellgren and Lawrence assessed by two observers. * Chronic knee pain with mechanical characteristics. * No local or systemic septic process. * Haematological and biochemical analysis without significant alterations that contraindicate treatment. * Informed written consent of the patient. * The patient is able to understand the nature of the study
Exclusion criteria
* Age over 75 or under 18 years or legally dependent * Present Infection (to be included in the study no signs of infection must be evidenced) * Congenital or acquired malformation resulting in significant deformity of the knee (varus\<10º; valgus\<20º) and leading to problems in application or evaluation of results. * Overweight expressed as body mass index (BMI) greater than 30.5 (obesity grade II). BMI estimated as mass (kg) / corporal surface (m2). * Women who are pregnant or intend to become pregnant or breast-feeding * Neoplasia * Immunosuppressive states * Intra-articular infiltartion of any treatments in the last 3 months previous to study inclusion * Participation in another clinical trial or treatment with a different investigational product within 30 days prior to inclusion in the study. * Other pathologic conditions or circumstances that difficult participation in the study according to medical criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Up to one year | Adverse events reported. Clinical review and questionaires for pain, disability and quality of life at 0, 3, 6 and 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | up to one year | Clinical review, questionaires for pain, disability and quality of life at 0, 3, 6 and 12 months. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index): Questionnaire to quantify the pain, stiffness and physical function in patients with osteoarthritis of the knee or hip. SF-12 (Short Form 12, an abbreviated form of SF36) is a questionnaire for the detection of changes in quality of life. The visual analogue scale (VAS) is a psychometric response scale which can be used for subjective measurements of knee pain. LEQUESNE algofunctional index: is a composite measure of pain and disability, with specific self-report questionnaires for knee (osteoarthritis). All the scale ranges ranges (minimum and maximum scores) are between 0 and 100%. Values are given in differences from baseline (usually negative values). More negative values show more improvement on both scales. |
| Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) | up to one year | Magnetic Resonance imaging measurements of T2 relaxation (Cartigram) performed at 0, 6 and 12 months to quantify articular cartilage degeneration. The values (in milliseconds) are T1/2 for decay of the T2 MRI signals. Normal values are below 50 ms; values above 50 ms correspond to inflamed cartilage. Mean (SD) are expressed as the number of values (of a total of 88 measurements) that are between 50 and 90 ms. A value =\<4.4 is considered normal (can be attained by chance). Values above 4.4 are considered pathological. The worst possible is 88. |
Countries
Spain
Participant flow
Recruitment details
30 patients were included between 26/Jul/2012 (Pat. 01) and12/Dic/2012 (Pat. 30).
Pre-assignment details
All patients fulfilled the selection criteria, were randomized and received the assigned medication.
Participants by arm
| Arm | Count |
|---|---|
| Allogenic Mesenchymal Stromal Cells Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intraarticular injection of 40 millions MSC.
Injection of Mesenchymal Stromal Cells: Mesenchymal stem cells prepared from bone marrow of healthy donors and expanded for 3-4 weeks according to our procedure described in PEI Num. 10-134, authorized by the Spanish Medicine Agency | 15 |
| Hyaluronic Acid (Durolane) Intraarticular injection of hyaluronic acid (60 mg)
Hyaluronic Acid: Intra-articular injection of 60 mg of hyaluronic acid (Durolane) in a single injection (3 ml) | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Allogenic Mesenchymal Stromal Cells | Total | Hyaluronic Acid (Durolane) |
|---|---|---|---|
| Age, Continuous | 56.60 years STANDARD_DEVIATION 9.57 | 56.97 years STANDARD_DEVIATION 9.33 | 57.33 years STANDARD_DEVIATION 9.41 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 30 Participants | 15 Participants |
| Region of Enrollment Spain | 15 participants | 30 participants | 15 participants |
| Sex: Female, Male Female | 7 Participants | 17 Participants | 10 Participants |
| Sex: Female, Male Male | 8 Participants | 13 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 15 | 13 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Adverse events reported. Clinical review and questionaires for pain, disability and quality of life at 0, 3, 6 and 12 months
Time frame: Up to one year
Population: Efficacy evaluable patients (EEP): A patient has been considered evaluable whenever it has undergone the specified interventions (injection of hyaluronic acid or allogeneic MSC).~and~Safety population (SP): The population that includes all evaluable patients who have undergone one of the two study treatments.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Allogenic Mesenchymal Stromal Cells | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 14 participants |
| Hyaluronic Acid (Durolane) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 13 participants |
Secondary
Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram)
Magnetic Resonance imaging measurements of T2 relaxation (Cartigram) performed at 0, 6 and 12 months to quantify articular cartilage degeneration. The values (in milliseconds) are T1/2 for decay of the T2 MRI signals. Normal values are below 50 ms; values above 50 ms correspond to inflamed cartilage. Mean (SD) are expressed as the number of values (of a total of 88 measurements) that are between 50 and 90 ms. A value =\<4.4 is considered normal (can be attained by chance). Values above 4.4 are considered pathological. The worst possible is 88.
Time frame: up to one year
Population: The efficacy endpoint analysis will be based on all patients who have not committed major protocol violations, and have at least one assessment of efficacy of the end graft. 3 patients of the allogenic MSC treatment group were excluded from this analysis because of incomplete measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Allogenic Mesenchymal Stromal Cells | Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) | MRI. Nº of values between 50-90 per visit. 6 | 9.33 number of values (range 0-88) | Standard Deviation 4.5 |
| Allogenic Mesenchymal Stromal Cells | Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) | MRI. Change of Nº of measurements. 6 | -3.00 number of values (range 0-88) | Standard Deviation 2.5 |
| Allogenic Mesenchymal Stromal Cells | Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) | MRI.Nº of values between 50-90 per visit.12. | 8.25 number of values (range 0-88) | Standard Deviation 5.6 |
| Allogenic Mesenchymal Stromal Cells | Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) | MRI. Change of Nº of measurements.12 | -4.08 number of values (range 0-88) | Standard Deviation 6 |
| Allogenic Mesenchymal Stromal Cells | Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) | MRI. Nº of values between 50-90 per visit. 0 | 12.33 number of values (range 0-88) | Standard Deviation 3.5 |
| Hyaluronic Acid (Durolane) | Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) | MRI. Change of Nº of measurements.12 | -2.80 number of values (range 0-88) | Standard Deviation 4.1 |
| Hyaluronic Acid (Durolane) | Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) | MRI. Nº of values between 50-90 per visit. 0 | 13.53 number of values (range 0-88) | Standard Deviation 5.7 |
| Hyaluronic Acid (Durolane) | Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) | MRI. Nº of values between 50-90 per visit. 6 | 11.73 number of values (range 0-88) | Standard Deviation 7.5 |
| Hyaluronic Acid (Durolane) | Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) | MRI.Nº of values between 50-90 per visit.12. | 10.73 number of values (range 0-88) | Standard Deviation 5.5 |
| Hyaluronic Acid (Durolane) | Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) | MRI. Change of Nº of measurements. 6 | -1.80 number of values (range 0-88) | Standard Deviation 5.8 |
Secondary
Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores)
Clinical review, questionaires for pain, disability and quality of life at 0, 3, 6 and 12 months. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index): Questionnaire to quantify the pain, stiffness and physical function in patients with osteoarthritis of the knee or hip. SF-12 (Short Form 12, an abbreviated form of SF36) is a questionnaire for the detection of changes in quality of life. The visual analogue scale (VAS) is a psychometric response scale which can be used for subjective measurements of knee pain. LEQUESNE algofunctional index: is a composite measure of pain and disability, with specific self-report questionnaires for knee (osteoarthritis). All the scale ranges ranges (minimum and maximum scores) are between 0 and 100%. Values are given in differences from baseline (usually negative values). More negative values show more improvement on both scales.
Time frame: up to one year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - General Health 3 months | 0.12 units on a scale | Standard Deviation 22.5 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - General 6 months | -13.03 units on a scale | Standard Deviation 18.2 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - General 12 months | -13.47 units on a scale | Standard Deviation 22.8 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Dificulty 3 months | -8.51 units on a scale | Standard Deviation 22.8 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Dificulty 6 months | -14.53 units on a scale | Standard Deviation 19.8 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Dificulty 12 months | -12.59 units on a scale | Standard Deviation 23.1 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Stiffness 3 months | -4.77 units on a scale | Standard Deviation 30.5 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Stiffness 6 months | -3.17 units on a scale | Standard Deviation 23.8 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Stiffness 12 months | -10.67 units on a scale | Standard Deviation 31.1 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Pain 3 months | -10.01 units on a scale | Standard Deviation 23.7 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Pain 6 months | -13.02 units on a scale | Standard Deviation 19 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Pain 12 months | -16.30 units on a scale | Standard Deviation 23 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - General 3 months | -8.48 units on a scale | Standard Deviation 22.6 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - General Health 6 months | 10.64 units on a scale | Standard Deviation 22.8 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - General Health 12 month | 5.24 units on a scale | Standard Deviation 27.9 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical function 3 m | 10.00 units on a scale | Standard Deviation 36.4 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical function 6 m | 13.33 units on a scale | Standard Deviation 26.5 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical function 12 m | 21.67 units on a scale | Standard Deviation 22.9 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical rol 3 months | 2.50 units on a scale | Standard Deviation 21.2 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical rol 6 months | 6.67 units on a scale | Standard Deviation 38.9 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical rol 12 months | 5.00 units on a scale | Standard Deviation 34 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Emotional rol 3 months | -1.67 units on a scale | Standard Deviation 22.6 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Emotional rol 6 months | 5.83 units on a scale | Standard Deviation 33 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Emotional rol 12 months | 0.00 units on a scale | Standard Deviation 31 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Body pain 3 months | 10.0 units on a scale | Standard Deviation 26.4 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Body pain 6 months | 15.00 units on a scale | Standard Deviation 28 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Body pain 12 months | 13.33 units on a scale | Standard Deviation 36.4 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 3 months | -5.83 units on a scale | Standard Deviation 24.5 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 6 months | 3.33 units on a scale | Standard Deviation 25.2 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 12 months | 0.00 units on a scale | Standard Deviation 14.2 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Vitality 3 months | -6.67 units on a scale | Standard Deviation 37.2 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Vitality 6 months | -1.67 units on a scale | Standard Deviation 33.4 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Vitality 12 months | -8.33 units on a scale | Standard Deviation 36.2 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Social function 3 mo | -1.67 units on a scale | Standard Deviation 27.5 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Social function 6 mo | 6.67 units on a scale | Standard Deviation 27.5 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Social function 12 mo | 6.67 units on a scale | Standard Deviation 29.1 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical Health 3 mo | 3.44 units on a scale | Standard Deviation 7.8 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical Health 6 mo | 4.51 units on a scale | Standard Deviation 7 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical Health 12 mo | 5.42 units on a scale | Standard Deviation 9.3 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 3 mo | -3.56 units on a scale | Standard Deviation 10.5 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 6 mo | 0.44 units on a scale | Standard Deviation 11.7 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 12 mo | -2.41 units on a scale | Standard Deviation 8.2 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | VAS_Changes from Basal - 3 months | -13.67 units on a scale | Standard Deviation 30.7 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | VAS_Changes from Basal - 6 months | -20.67 units on a scale | Standard Deviation 29.3 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | VAS_Changes from Basal - 12 months | -21.20 units on a scale | Standard Deviation 28.5 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | LEQUESNE_Changes from Basal - 3 months | -3.63 units on a scale | Standard Deviation 12.4 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | LEQUESNE_Changes from Basal - 6 months | -13.95 units on a scale | Standard Deviation 10.8 |
| Allogenic Mesenchymal Stromal Cells | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | LEQUESNE_Changes from Basal - 12 months | -8.76 units on a scale | Standard Deviation 12.4 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | LEQUESNE_Changes from Basal - 6 months | -5.46 units on a scale | Standard Deviation 13.4 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - General 3 months | -4.52 units on a scale | Standard Deviation 17.4 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Body pain 3 months | 5.00 units on a scale | Standard Deviation 28.7 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - General 6 months | -5.47 units on a scale | Standard Deviation 15.9 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical Health 3 mo | 3.71 units on a scale | Standard Deviation 7.6 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - General 12 months | -4.10 units on a scale | Standard Deviation 18.4 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Body pain 6 months | 11.67 units on a scale | Standard Deviation 26.5 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Dificulty 3 months | -6.46 units on a scale | Standard Deviation 18.7 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | VAS_Changes from Basal - 3 months | -7.53 units on a scale | Standard Deviation 23.6 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Dificulty 6 months | -6.97 units on a scale | Standard Deviation 20.5 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Body pain 12 months | 13.33 units on a scale | Standard Deviation 24.8 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Dificulty 12 months | -4.26 units on a scale | Standard Deviation 21.3 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical Health 6 mo | 3.76 units on a scale | Standard Deviation 9.3 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Stiffness 3 months | -1.93 units on a scale | Standard Deviation 25.2 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 3 months | 3.33 units on a scale | Standard Deviation 19.7 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Stiffness 6 months | -2.87 units on a scale | Standard Deviation 23.6 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | LEQUESNE_Changes from Basal - 3 months | -5.18 units on a scale | Standard Deviation 12.8 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Stiffness 12 months | -4.50 units on a scale | Standard Deviation 29.5 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 6 months | 3.33 units on a scale | Standard Deviation 19.7 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Pain 3 months | -4.27 units on a scale | Standard Deviation 17.2 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical Health 12 mo | 4.59 units on a scale | Standard Deviation 9.3 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Pain 6 months | -5.97 units on a scale | Standard Deviation 12.1 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 12 months | 5.00 units on a scale | Standard Deviation 18.8 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | WOMAC11_Changes from Basal - Pain 12 months | -6.36 units on a scale | Standard Deviation 15.8 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | VAS_Changes from Basal - 6 months | -11.93 units on a scale | Standard Deviation 20.6 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - General Health 3 months | 0.39 units on a scale | Standard Deviation 16.2 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Vitality 3 months | 1.67 units on a scale | Standard Deviation 25.8 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - General Health 6 months | 2.11 units on a scale | Standard Deviation 21.2 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 3 mo | -1.99 units on a scale | Standard Deviation 8.9 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - General Health 12 month | 2.51 units on a scale | Standard Deviation 21.1 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Vitality 6 months | 1.67 units on a scale | Standard Deviation 25.8 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical function 3 m | 18.33 units on a scale | Standard Deviation 30.6 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | LEQUESNE_Changes from Basal - 12 months | -3.13 units on a scale | Standard Deviation 12.6 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical function 6 m | 11.67 units on a scale | Standard Deviation 32.6 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Vitality 12 months | -6.67 units on a scale | Standard Deviation 24 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical function 12 m | 20.00 units on a scale | Standard Deviation 30.2 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 6 mo | -1.09 units on a scale | Standard Deviation 7 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical rol 3 months | 4.17 units on a scale | Standard Deviation 31.2 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Social function 3 mo | -1.67 units on a scale | Standard Deviation 27.5 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical rol 6 months | 9.17 units on a scale | Standard Deviation 29.7 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | VAS_Changes from Basal - 12 months | -13.07 units on a scale | Standard Deviation 21.6 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Physical rol 12 months | 6.67 units on a scale | Standard Deviation 30.6 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Social function 6 mo | -6.67 units on a scale | Standard Deviation 29.1 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Emotional rol 3 months | -5.83 units on a scale | Standard Deviation 24.5 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Mental Health 12 mo | -1.56 units on a scale | Standard Deviation 9.1 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Emotional rol 6 months | 1.67 units on a scale | Standard Deviation 15.6 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Social function 12 mo | 0.00 units on a scale | Standard Deviation 26.7 |
| Hyaluronic Acid (Durolane) | Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) | SF-12_Changes from Basal - Emotional rol 12 months | 0.83 units on a scale | Standard Deviation 18 |