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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-005321-51 | EudraCT Number | ||
| EC11-309 | Other Grant/Funding Number | Spanish Ministry of Health, Independent Clinical Investigatio | |
| MSV_allo | Registry Identifier | Protocol code |
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| Name | Class |
|---|---|
| University of Valladolid | OTHER |
| Sanidad de Castilla y León | OTHER |
| Centro Medico Teknon | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Allogenic mesenchymal stromal cells injection | Experimental | Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intraarticular injection of 40 millions MSC. |
|
| Hyaluronic acid (Durolane) | Active Comparator | Intraarticular injection of hyaluronic acid (60 mg) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogenic mesenchymal stromal cells injection | Other | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Up to one year |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Javier García-Sancho, MD, PhD | University of Valladolid, Scientific Park | Study Chair |
| Aurelio Vega, MD,PhD | Hospital Clinico Universitario, Valladolid | Study Director |
| Luis Orozco, MD, PhD | Centro Médico Teknon, Barcelona | Study Director |
| Ana Sanchez, MD, PhD | Director, Cell Production Unit, Parque Científico UVa | Study Director |
| Jose M Moraleda, MD. PhD | Virgen de la Arrixaca University Hospital, Murcia, Spain | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centro Medico Teknon | Barcelona | Barcelona | 08022 | Spain | ||
| Hospital Clinico Universitario |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21792091 | Background | Orozco L, Soler R, Morera C, Alberca M, Sanchez A, Garcia-Sancho J. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation. 2011 Oct 15;92(7):822-8. doi: 10.1097/TP.0b013e3182298a15. | |
| 23680930 | Background | Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentis J, Sanchez A, Garcia-Sancho J. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation. 2013 Jun 27;95(12):1535-41. doi: 10.1097/TP.0b013e318291a2da. |
| Label | URL |
|---|---|
| Cell Therapy Network | View source |
Not provided
All patients fulfilled the selection criteria, were randomized and received the assigned medication.
30 patients were included between 26/Jul/2012 (Pat. 01) and12/Dic/2012 (Pat. 30).
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | 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. | Posted | Number | participants | Up to one year |
|
1 year
All patients completed the study successfully. The mean duration of the patients in the study was 12.4 (± 0.6) months, 12.5 (± 0.8) months in the MSV group and 12.4 (± 0.3) months in the hyaluronic acid group.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Artralgia | Musculoskeletal and connective tissue disorders | MedDRA v16.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Javier Garcia-Sancho | Instituto de Biología y Genética Molecular (IBGM) | 34 983 423 084 | jgsancho@ibgm.uva.es |
Not provided
| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| D010003 | Osteoarthritis |
| D009140 | Musculoskeletal Diseases |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D012216 | Rheumatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D006820 | Hyaluronic Acid |
| ID | Term |
|---|---|
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Hyaluronic Acid | Drug | Intra-articular injection of 60 mg of hyaluronic acid (Durolane) in a single injection (3 ml) |
|
|
| up to one year |
| 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. | up to one year |
| Valladolid |
| Valladolid |
| 47003 |
| Spain |
| 24887752 | Background | Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentis J, Sanchez A, Garcia-Sancho J. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-year follow-up results. Transplantation. 2014 Jun 15;97(11):e66-8. doi: 10.1097/TP.0000000000000167. No abstract available. |
| 25822648 | Derived | Vega A, Martin-Ferrero MA, Del Canto F, Alberca M, Garcia V, Munar A, Orozco L, Soler R, Fuertes JJ, Huguet M, Sanchez A, Garcia-Sancho J. Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial. Transplantation. 2015 Aug;99(8):1681-90. doi: 10.1097/TP.0000000000000678. |
| MSV providing | View source |
| osteoarthritis, knee | View source |
| mesenchymal stem cells | View source |
| BG001 | 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) |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 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) |
|
|
| 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. | Posted | Mean | Standard Deviation | units on a scale | up to one year |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | number of values (range 0-88) | up to one year |
|
|
|
| 0 |
| 15 |
| 14 |
| 15 |
| EG001 | 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) | 0 | 15 | 13 | 15 |
| Joint Effusion | Musculoskeletal and connective tissue disorders | MedDRA v16.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v16.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA v16.0 | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA v16.0 | Systematic Assessment |
|
| Nasofaringitis | Infections and infestations | MedDRA v16.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA v16.0 | Systematic Assessment |
|
| Rinitis | Infections and infestations | MedDRA v16.0 | Systematic Assessment |
|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v16.0 | Systematic Assessment |
|
| Neoplasia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v16.0 | Systematic Assessment |
|
| Dental implant | Surgical and medical procedures | MedDRA v16.0 | Systematic Assessment |
|
| Allergic dermatitis | Skin and subcutaneous tissue disorders | MedDRA v16.0 | Systematic Assessment |
|
| Amenorrhea | Reproductive system and breast disorders | MedDRA v16.0 | Systematic Assessment |
|
| Testicular pain | Reproductive system and breast disorders | MedDRA v16.0 | Systematic Assessment |
|
| Premature menopause | Reproductive system and breast disorders | MedDRA v16.0 | Systematic Assessment |
|
| Menorrhagia | Reproductive system and breast disorders | MedDRA v16.0 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA v16.0 | Systematic Assessment |
|
| Amnesia | Nervous system disorders | MedDRA v16.0 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA v16.0 | Systematic Assessment |
|
| Drowsiness | Nervous system disorders | MedDRA v16.0 | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | MedDRA v16.0 | Systematic Assessment |
|
| Dental pain | Gastrointestinal disorders | MedDRA v16.0 | Systematic Assessment |
|
| Leak | General disorders | MedDRA v16.0 | Systematic Assessment |
|
| Artralgia/Artritis | Musculoskeletal and connective tissue disorders | MedDRA v16.0 | Systematic Assessment |
|
| Arthralgia/Effusion | Musculoskeletal and connective tissue disorders | MedDRA v16.0 | Systematic Assessment |
|
| Corneal erosion / Blepharitis | Eye disorders | MedDRA v16.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA v16.0 | Systematic Assessment |
|
| Nervousness | Psychiatric disorders | MedDRA v16.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA v16.0 | Systematic Assessment |
|
The only disclosure restriction on the PI is that the sponsor must review results communications prior to public release.
| WOMAC11_Changes from Basal - General 12 months |
|
| WOMAC11_Changes from Basal - Dificulty 3 months |
|
| WOMAC11_Changes from Basal - Dificulty 6 months |
|
| WOMAC11_Changes from Basal - Dificulty 12 months |
|
| WOMAC11_Changes from Basal - Stiffness 3 months |
|
| WOMAC11_Changes from Basal - Stiffness 6 months |
|
| WOMAC11_Changes from Basal - Stiffness 12 months |
|
| WOMAC11_Changes from Basal - Pain 3 months |
|
| WOMAC11_Changes from Basal - Pain 6 months |
|
| WOMAC11_Changes from Basal - Pain 12 months |
|
| SF-12_Changes from Basal - General Health 3 months |
|
| SF-12_Changes from Basal - General Health 6 months |
|
| SF-12_Changes from Basal - General Health 12 month |
|
| SF-12_Changes from Basal - Physical function 3 m |
|
| SF-12_Changes from Basal - Physical function 6 m |
|
| SF-12_Changes from Basal - Physical function 12 m |
|
| SF-12_Changes from Basal - Physical rol 3 months |
|
| SF-12_Changes from Basal - Physical rol 6 months |
|
| SF-12_Changes from Basal - Physical rol 12 months |
|
| SF-12_Changes from Basal - Emotional rol 3 months |
|
| SF-12_Changes from Basal - Emotional rol 6 months |
|
| SF-12_Changes from Basal - Emotional rol 12 months |
|
| SF-12_Changes from Basal - Body pain 3 months |
|
| SF-12_Changes from Basal - Body pain 6 months |
|
| SF-12_Changes from Basal - Body pain 12 months |
|
| SF-12_Changes from Basal - Mental Health 3 months |
|
| SF-12_Changes from Basal - Mental Health 6 months |
|
| SF-12_Changes from Basal - Mental Health 12 months |
|
| SF-12_Changes from Basal - Vitality 3 months |
|
| SF-12_Changes from Basal - Vitality 6 months |
|
| SF-12_Changes from Basal - Vitality 12 months |
|
| SF-12_Changes from Basal - Social function 3 mo |
|
| SF-12_Changes from Basal - Social function 6 mo |
|
| SF-12_Changes from Basal - Social function 12 mo |
|
| SF-12_Changes from Basal - Physical Health 3 mo |
|
| SF-12_Changes from Basal - Physical Health 6 mo |
|
| SF-12_Changes from Basal - Physical Health 12 mo |
|
| SF-12_Changes from Basal - Mental Health 3 mo |
|
| SF-12_Changes from Basal - Mental Health 6 mo |
|
| SF-12_Changes from Basal - Mental Health 12 mo |
|
| VAS_Changes from Basal - 3 months |
|
| VAS_Changes from Basal - 6 months |
|
| VAS_Changes from Basal - 12 months |
|
| LEQUESNE_Changes from Basal - 3 months |
|
| LEQUESNE_Changes from Basal - 6 months |
|
| LEQUESNE_Changes from Basal - 12 months |
|
| MRI.Nº of values between 50-90 per visit.12. |
|
| MRI. Change of Nº of measurements. 6 |
|
| MRI. Change of Nº of measurements.12 |
|