Overview

This trial is active, not recruiting.

Condition osteoarthritis
Treatments hyaluronic acid, 10 million bone marrow mesenchimal stem cells, 100 million bone marrow mesenchimal stem cells
Phase phase 1/phase 2
Sponsor Clinica Universidad de Navarra, Universidad de Navarra
Start date May 2012
End date November 2014
Trial size 30 participants
Trial identifier NCT02123368, 2009-017624-72, CMM/ART

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Single intraarticular injection of Hyaluronic acid (Hyal One)
hyaluronic acid HyalOne
Single intraarticular injection of Hyaluronic acid (Hyal One)
(Active Comparator)
Single intraarticular injection of Hyaluronic acid (Hyal One) 10 million Bone marrow mesenchimal stem cells
hyaluronic acid HyalOne
Single intraarticular injection of Hyaluronic acid (Hyal One)
10 million bone marrow mesenchimal stem cells 10 million Bone marrow mesenchimal stem cells
10 million of Bone marrow mesenchimal stem cells
(Active Comparator)
Single intraarticular injection of Hyaluronic acid (Hyal One) 100 million Bone marrow mesenchimal stem cells
hyaluronic acid HyalOne
Single intraarticular injection of Hyaluronic acid (Hyal One)
100 million bone marrow mesenchimal stem cells 100 million Bone marrow mesenchimal stem cells
100 million of Bone marrow mesenchimal stem cells

Primary Outcomes

Measure
Baseline Visual analogue scale (VAS)
time frame: prior to the initial dose on day 1
Baseline value of knee injury and osteoarthritis outcome score (Koos).
time frame: Prior to the intervention on day 1
Baseline Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC).
time frame: Prior to the intervention on day 1
Baseline SF-36 value
time frame: Prior to the intervention on day 1
Baseline euroquol 5D value
time frame: Prior to the intervention on day 1
Baseline Lequesne index
time frame: Prior to the intervention on day 1
Baseline femorotibial distance
time frame: Prior to the intervention
Number of Participants with Serious and Non-Serious Adverse Events Number of Participants with Serious and Non-Serious Adverse Events Number of Participants with Serious and Non-Serious Adverse Events
time frame: Follow up
Visual analogue scale (VAS) at on month
time frame: 1 month
Visual analogue scale (VAS) at 3 months
time frame: 3 months
Visual analogue scale (VAS) at 6 months
time frame: 6 months
Visual analogue scale (VAS) at 12 months
time frame: 12 months
Value of knee injury and osteoarthritis outcome score (Koos) at 1 month
time frame: 1 month
Value of knee injury and osteoarthritis outcome score (Koos) at 3 month
time frame: 3 Months
Value of knee injury and osteoarthritis outcome score (Koos) at 6 month
time frame: 6 months
Value of knee injury and osteoarthritis outcome score (Koos) at 12 months
time frame: 12 months
Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month
time frame: 1 month
Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 3 month
time frame: 3 months
Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month
time frame: 6 months
Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months
time frame: 12 months
SF-36 value at 1 month
time frame: 1 month
SF 36 value at 3 months
time frame: 3 months
SF 36 value at 6 months
time frame: 6 months
SF 36 value at 12 months
time frame: 12 months
Euroquol 5D value at 1 month
time frame: 1 MOnth
Euroquol 5D value at 3 months
time frame: 3 months
Euroquol 5D value at 6 months
time frame: 6 months
Euroquol 5D value at 12 months
time frame: 12 months
Lequesne index at 1 month
time frame: 1 month
Lequesne index at 3 months
time frame: 3 months
Lequesne index at 6 months
time frame: 6 months
Lequesne index at 12 months
time frame: 12 months
Femorotibial distance at 6 months
time frame: 6 months
Femorotibial distance at 12 months
time frame: 12 months
Baseline MRI WORMS protocol
time frame: Prior to the intervention
MRI WORMS protocol score at 6 months
time frame: 6 months
MRI WORMS protocol score at 12 months
time frame: 12 months

Eligibility Criteria

Male or female participants from 50 years up to 80 years old.

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.

Additional Information

Official title Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells
Principal investigator José Lamo-Espinosa, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2015.
Information provided to ClinicalTrials.gov by Clinica Universidad de Navarra, Universidad de Navarra.