Treatment of Knee Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells
- Conditions
- Osteoarthritis
- Interventions
- Biological: 10 million Bone marrow mesenchimal stem cellsBiological: 100 million Bone marrow mesenchimal stem cells
- Registration Number
- NCT02123368
- Lead Sponsor
- Clinica Universidad de Navarra, Universidad de Navarra
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Hyaluronic acid and MSC 10 10 million Bone marrow mesenchimal stem cells Single intraarticular injection of Hyaluronic acid (Hyal One) 10 million Bone marrow mesenchimal stem cells Hyaluronic acid AND MSC 100 Hyaluronic acid Single intraarticular injection of Hyaluronic acid (Hyal One) 100 million Bone marrow mesenchimal stem cells Hyaluronic acid AND MSC 100 100 million Bone marrow mesenchimal stem cells Single intraarticular injection of Hyaluronic acid (Hyal One) 100 million Bone marrow mesenchimal stem cells Hialuronic acid Hyaluronic acid Single intraarticular injection of Hyaluronic acid (Hyal One) Hyaluronic acid and MSC 10 Hyaluronic acid Single intraarticular injection of Hyaluronic acid (Hyal One) 10 million Bone marrow mesenchimal stem cells
- Primary Outcome Measures
Name Time Method SF 36 value at 6 months 6 months SF 36 value at 6 months
Baseline Visual analogue scale (VAS) prior to the initial dose on day 1 Baseline Visual analogue scale (VAS)
Baseline Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC). Prior to the intervention on day 1 Prior to the intervention on day 1 Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC).
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 Follow up During the follow up
Visual analogue scale (VAS) at 3 months 3 months Visual analogue scale (VAS) at 3 months
Visual analogue scale (VAS) at 12 months 12 months Visual analogue scale (VAS) at 12 months
Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month 6 months Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month
Baseline value of knee injury and osteoarthritis outcome score (Koos). Prior to the intervention on day 1 Prior to the intervention on day 1 value of knee injury and osteoarthritis outcome score (Koos).
Visual analogue scale (VAS) at 6 months 6 months Visual analogue scale (VAS) at 6 months
Baseline SF-36 value Prior to the intervention on day 1 Prior to the intervention on day 1 SF-36 value
Baseline euroquol 5D value Prior to the intervention on day 1 Pretreatment euroquol 5D value
Baseline femorotibial distance Prior to the intervention Prior to the intervention femoritibial distance on rosenberg x-ray view
Baseline Lequesne index Prior to the intervention on day 1 Prior to the intervention on day 1 Lequesne index
Value of knee injury and osteoarthritis outcome score (Koos) at 3 month 3 Months Value of knee injury and osteoarthritis outcome score (Koos) at 3 month
Visual analogue scale (VAS) at on month 1 month Visual analogue scale (VAS) at on month
Value of knee injury and osteoarthritis outcome score (Koos) at 1 month 1 month Value of knee injury and osteoarthritis outcome score (Koos) at 1 month
Value of knee injury and osteoarthritis outcome score (Koos) at 6 month 6 months Value of knee injury and osteoarthritis outcome score (Koos) at 6 month
Value of knee injury and osteoarthritis outcome score (Koos) at 12 months 12 months Value of knee injury and osteoarthritis outcome score (Koos) at 12 months
Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month 1 month Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month
Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 3 month 3 months Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month
SF 36 value at 3 months 3 months SF 36 value at 3 months
SF 36 value at 12 months 12 months SF 36 value at 12 months
Euroquol 5D value at 6 months 6 months Euroquol 5D value at 6 months
Euroquol 5D value at 12 months 12 months Euroquol 5D value at 12 months
Lequesne index at 1 month 1 month Lequesne index at 1 month
Lequesne index at 3 months 3 months Lequesne index at 3 months
Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months 12 months Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months
SF-36 value at 1 month 1 month SF-36 value
Euroquol 5D value at 1 month 1 MOnth Euroquol 5D value at 1 month
Femorotibial distance at 6 months 6 months Femorotibial distance at 6 months
MRI WORMS protocol score at 12 months 12 months MRI WORMS protocol score at 12 months
Euroquol 5D value at 3 months 3 months Euroquol 5D value at 3 months
MRI WORMS protocol score at 6 months 6 months MRI WORMS protocol score at 6 months
Lequesne index at 6 months 6 months Lequesne index at 6 months
Lequesne index at 12 months 12 months Lequesne index at 12 months
Femorotibial distance at 12 months 12 months Femorotibial distance at 12 months
Baseline MRI WORMS protocol Prior to the intervention Prior to the intervention MRI WORMS protocol
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (2)
Orthopaedic and traumatology department. Clínica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Traumatology department. Complejo Hospitalario de Salamanca
🇪🇸Salamanca, Castilla y León, Spain