Adult Stem Cell Therapy for Repairing Articular Cartilage in Gonarthrosis

Study Overview
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Brief Summary
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This is a prospective, open-label, single-dose, single-arm phase I-II study in which 15 patients diagnosed with gonarthrosis grade II-III (Kellgren and Lawrence) will enter the study with the primary objective of assessing the feasibility and safety of the knee articular infiltration of autologous bone marrow mesenchymal stem cells (MSC). Secondary objectives are to assess the efficacy by imaging procedures and clinical questionnaires. MSC obtained from each patient's bone marrow will be isolated and expanded Ex-Vivo under GMP conditions at Xcelia-División de Terapias avanzadas del Banc de Sang I Teixits. After 21 days, patients will be implanted a single-dose of approximately 40 millions of autologous MSC in the knee by articular injection, and followed up for 12 month. Articular cartilage changes will be determined by T2-weighted MRI (Cartigram) at 6 and 12 month. Clinical assessment will measure the pain by the visual analogue scale (VAS), the self-reported functional status by Heath Assessment Questionnaire (HAQ), and the quality of life by Short Form 36 questionnaire (SF-36) at 3, 6 and 12 month. The working hypothesis proposes that the expected regenerative articular cartilage effect of the MSC will be produced to a measurable degree by imaging procedures and clinical questionnaires.

Official Title
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Articular Cartilage Regeneration in Gonarthrosis Grade II and III by Articular Infiltration of Xcel-m-condro-alpha.

Conditions
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Osteoarthritis, Knee, Knee Injuries, Joint Diseases, Rheumatic Diseases, Cartilage Diseases

Intervention / Treatment
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* Other: Autologous MSC knee implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gonarthrosis grade II-III of Kellgren and Lawrence assessed by two observers Chronic knee pain with mechanical characteristics Absence of local or systemic septic process Haematological and biochemical laboratory tests without significant alterations that contraindicate treatment. Informed Consent form signed by the patient The patient is able to understand the nature of the study Exclusion Criteria: Patients < 18 years or legally dependent Patients >65 years Previous surgery of the knee Intraarticular treatment in the past 6 month Knee ligament or meniscus rupture observed by MRI Any sign of infection Positive serology for HIV-1 or HIV-2, Hepatitis B (HBsAg), Hepatitis C (Anti-HCV-Ab) and syphilis. Congenital or acquired malformation resulting in significant deformity of the knee 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). Pregnant women or intend to become pregnant or breast-feeding Neoplasia Immunosuppressive states 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous MSC knee implantation<br>Isolation and Ex-Vivo expansion of Mesenchymal stem cells (MSC) obtained from each patient's bone marrow under GMP conditions at Xcelia-División de Terapias Avanzadas del Banc de Sang I Teixits. After 21 days, approximately 40 millions of autologous MSC will be implanted in the knee by articular injection. | Other: Autologous MSC knee implantation<br>* Isolation and Ex-Vivo expansion of Mesenchymal stem cells (MSC) obtained from each patient's bone marrow under GMP conditions at Xcelia-División de Terapias avanzadas del Banc de Sang I Teixits. After 21 days, approximately 40 millions of autologous MSC will be implanted in the knee by articular injection.<br>* Other names: Xcel-m-condro-alpha;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of autologous bone marrow mesenchymal stem cells (MSC) knee articular infiltration. | Feasibility will be assessed by checking the cascade of procedures (from bone marrow extraction to MSC implantation) and confirming the global process is viable. | 12 months | 
| Safety of autologous bone marrow mesenchymal stem cells (MSC) knee articular infiltration. | Safety will be assessed by collecting adverse events throughout the experimental phase, including the follow-up at 12 months. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy by imaging procedures. | Articular cartilage changes will be determined by T2-weighted MRI (Cartigram). | 6 months | 
| Efficacy by imaging procedures. | Articular cartilage changes will be determined by T2-weighted MRI (Cartigram). | 12 month | 
| Clinical outcomes. | Clinical assessment will measure the pain by the visual analogue scale (VAS), the self-reported functional status by Heath Assessment Questionnaire (HAQ), and the quality of life by Short Form 36 questionnaire (SF-36). | 3 month | 
| Clinical outcomes. | Clinical assessment will measure the pain by the visual analogue scale (VAS), the self-reported functional status by Heath Assessment Questionnaire (HAQ), and the quality of life by Short Form 36 questionnaire (SF-36). | 6 months | 
| Clinical outcomes. | Clinical assessment will measure the pain by the visual analogue scale (VAS), the self-reported functional status by Heath Assessment Questionnaire (HAQ), and the quality of life by Short Form 36 questionnaire (SF-36). | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell therapy, Regenerative therapy, Advance therapy, Bone marrow, Mesenchymal stem cell, Autologous, Interventional clinical trial, Osteoarthrosis, Osteoarthritis, Knee