Treatment of Knee Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells

University of Navarra

Status and phase: Completed; Phase 2; Phase 1

Conditions: Osteoarthritis

Treatments: Drug: Hyaluronic acid; Biological: 10 million Bone marrow mesenchimal stem cells; Biological: 100 million Bone marrow mesenchimal stem cells

Study type: Interventional

Funder types: Other

Identifiers

NCT02123368

2009-017624-72 (EudraCT Number)

CMM/ART

Details and patient eligibility

About

Purpose: To determine the safety, feasibility and effectiveness (clinical and radiological) of intra-articular administration of autologous mesenchymal stem cells (MSCs) in patients with knee osteoarthritis.

Patients and methods

Clinical trial phase I- II, randomized , multicenter , with three treatment arms and 10 patients for each group. The investigators compare the intraarticular injection of hialuronic acid against the administration of two different doses of mesenchymal stem cells with hialuronic acid according to the following scheme:

1. Group A: intra-articular injection of hyaluronic acid (Hyalone®). Single dose.
2. Group B: Low Dosage of MSCs . Intra-articular injection of 10 million autologous mesenchymal progenitor stem cells cultured ex - vivo (cell suspension sterile small volume (5-10 ml ) in a vehicle suitable for intraarticular injection ) followed by an intraarticular injection Hiaurónico Acid ( Hyalone®).
3. Group C : High dose of MSCs. Intra-articular injection of 100 million autologous mesenchymal progenitor stem cells cultured ex - vivo ( cell suspension sterile small volume (5-10 ml ) in a vehicle suitable for intraarticular injection ) followed by an intraarticular injection Hiaurónico Acid (Hyalone®).

The primary endpoint is safety and feasibility. The investigators registered the occurrence of complications and / or adverse effects during the study.

In addition the investigators assess the response to intra-articular infusion of CMM analyzing the following parameters:

• Clinical assessment of pain and function (Baseline, 1, 3, 6 and 12 months since treatment): VAS , WOMAC , KOOS , EuroQol, SF-16, Lequesne , WOMAC , KOOS.
• Radiographic (baseline, 6 and 12 months since treatment): Femorotibial space.
• Radiographic using MRI (baseline, 6 and 12 months since treatment): by assessing the number location of the lesions , cartilage thickness , signal intensity , subchondral bone alteration , volume and WORMS and dGEMRIC protocols.

Full description

Purpose: To determine the safety, feasibility and effectiveness (clinical and radiological) of intra-articular administration of autologous mesenchymal stem cells (MSCs) in patients with knee osteoarthritis.

Patients and methods

Clinical trial phase I- II, randomized , multicenter , with three treatment arms and 10 patients for each group. The investigators compare the intraarticular injection of hialuronic acid against the administration of two different doses of mesenchymal stem cells with hialuronic acid according to the following scheme:

1. Group A: intra-articular injection of hyaluronic acid (Hyalone®). Single dose.
2. Group B: Low Dosage of MSCs . Intra-articular injection of 10 million autologous mesenchymal progenitor stem cells cultured ex - vivo (cell suspension sterile small volume (5-10 ml ) in a vehicle suitable for intraarticular injection ) followed by an intraarticular injection Hiaurónico Acid ( Hyalone®).
3. Group C : High dose of MSCs. Intra-articular injection of 100 million autologous mesenchymal progenitor stem cells cultured ex - vivo ( cell suspension sterile small volume (5-10 ml ) in a vehicle suitable for intraarticular injection ) followed by an intraarticular injection Hiaurónico Acid (Hyalone®).

The autologous mesenchymal stem cells are obtained from the iliac crest and cultured ex vivo under local anesthesia and sedation.

The primary endpoint is safety and feasibility. The investigators registered the occurrence of complications and / or adverse effects during the study.

In addition the investigators assess the response to intra-articular infusion of CMM analyzing the following parameters:

• Clinical assessment of pain and function (Baseline, 1, 3, 6 and 12 months since treatment): VAS , WOMAC , KOOS , EuroQol, SF-16, Lequesne , WOMAC , KOOS.
• Radiographic (baseline, 6 and 12 months since treatment): Femorotibial space.
• Radiographic using MRI (baseline, 6 and 12 months since treatment): by assessing the number location of the lesions , cartilage thickness , signal intensity , subchondral bone alteration , volume and WORMS and dGEMRIC protocols.

All patients met the following inclusion and exclusion criteria:

Inclusion Criteria:

• Males and females between 50 and 80 year old.
• Diagnosis of knee OA according to the criteria of osteoarthritis of the ACR (American College of Rheumatology).
• Joint pain equal or greater than 2.5 points on the visual analogue scale (VAS).
• Radiological Classification: Kellgren-Lawrence scale greater or equal to 2.
• Body mass index between 20 and 35 kg/m2.
• Ability to follow during the study period.

Exclusion Criteria:

• Bilateral Osteoarthritis of the Knee requiring treatment in both knees.
• Previous diagnosis of polyarticular disease.
• Severe mechanical deformation.
• Arthroscopy during the previous 6 months.
• Intraarticular infiltration of hyaluronic acid in the last 6 months.
• Systemic autoimmune rheumatic disease.
• Poorly controlled diabetes mellitus.
• Blood dyscrasias.
• Immunosuppressive or anticoagulant treatments.
• Treatment with corticosteroids in the 3 months prior to inclusion in the study.
• NSAID therapy within 15 days prior to inclusion in the study.
• Patients with a history of allergy to penicillin or streptomycin.
• Allergy to hyaluronic acid or poultry proteins.

Enrollment: 30 patients

Sex: All

Ages: 50 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males and females between 50 and 80 year old.
• Diagnosis of knee OA according to the criteria of osteoarthritis of the ACR (American College of Rheumatology).
• Joint pain equal or greater than 2.5 points on the visual analogue scale (VAS).
• Radiological Classification: Kellgren-Lawrence scale greater or equal to 2.
• Body mass index between 20 and 35 kg/m2.
• Ability to follow during the study period.

Exclusion criteria

• Bilateral Osteoarthritis of the Knee requiring treatment in both knees.
• Previous diagnosis of polyarticular disease.
• Severe mechanical deformation.
• Arthroscopy during the previous 6 months.
• Intraarticular infiltration of hyaluronic acid in the last 6 months.
• Systemic autoimmune rheumatic disease.
• Poorly controlled diabetes mellitus.
• Blood dyscrasias.
• Immunosuppressive or anticoagulant treatments.
• Treatment with corticosteroids in the 3 months prior to inclusion in the study.
• NSAID therapy within 15 days prior to inclusion in the study.
• Patients with a history of allergy to penicillin or streptomycin.
• Allergy to hyaluronic acid or poultry proteins.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Hialuronic acid

Active Comparator group

Description:

Single intraarticular injection of Hyaluronic acid (Hyal One)

Treatment:

Drug: Hyaluronic acid

Hyaluronic acid and MSC 10

Active Comparator group

Description:

Single intraarticular injection of Hyaluronic acid (Hyal One) 10 million Bone marrow mesenchimal stem cells

Treatment:

Biological: 10 million Bone marrow mesenchimal stem cells

Drug: Hyaluronic acid

Hyaluronic acid AND MSC 100

Active Comparator group

Description:

Single intraarticular injection of Hyaluronic acid (Hyal One) 100 million Bone marrow mesenchimal stem cells

Treatment:

Biological: 100 million Bone marrow mesenchimal stem cells

Drug: Hyaluronic acid