Treatment of Knee Osteoarthritis With Allogenic Mesenchymal Stem Cells

Phase 1

Completed

Conditions: Osteoarthritis, Knee
Arthritis of Knee
Knee Osteoarthritis

Interventions: Other: Allogenic mesenchymal stromal cells injection
Drug: Hyaluronic Acid

Registration Number: NCT01586312

Lead Sponsor: Red de Terapia Celular

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Allogenic mesenchymal stromal cells injection	Allogenic mesenchymal stromal cells injection	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)	Hyaluronic Acid	Intraarticular injection of hyaluronic acid (60 mg)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.