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

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

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Osteoarthritis
Intervention	Drug: Hyaluronic acid Biological: 10 million Bone marrow mesenchimal stem cells Biological: 100 million Bone marrow mesenchimal stem cells
Phase	Phase 1/Phase 2
Sponsor	Clinica Universidad de Navarra, Universidad de Navarra
Responsible Party	Clinica Universidad de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier	NCT02123368
First Received	November 12, 2013
Last Updated	April 23, 2014
Last verified	April 2014

Tracking Information[ + expand ][ + ]

First Received Date	November 12, 2013
Last Updated Date	April 23, 2014
Start Date	May 2012
Estimated Primary Completion Date	November 2014
Current Primary Outcome Measures	Baseline Visual analogue scale (VAS) [Time Frame: prior to the initial dose on day 1] [Designated as safety issue: No]Baseline Visual analogue scale (VAS) Baseline value of knee injury and osteoarthritis outcome score (Koos). [Time Frame: Prior to the intervention on day 1] [Designated as safety issue: No]Prior to the intervention on day 1 value of knee injury and osteoarthritis outcome score (Koos). Baseline Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC). [Time Frame: Prior to the intervention on day 1] [Designated as safety issue: No]Prior to the intervention on day 1 Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC). Baseline SF-36 value [Time Frame: Prior to the intervention on day 1] [Designated as safety issue: No]Prior to the intervention on day 1 SF-36 value Baseline euroquol 5D value [Time Frame: Prior to the intervention on day 1] [Designated as safety issue: No]Pretreatment euroquol 5D value Baseline Lequesne index [Time Frame: Prior to the intervention on day 1] [Designated as safety issue: No]Prior to the intervention on day 1 Lequesne index Baseline femorotibial distance [Time Frame: Prior to the intervention] [Designated as safety issue: No]Prior to the intervention femoritibial distance on rosenberg x-ray view 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] [Designated as safety issue: Yes]During the follow up Visual analogue scale (VAS) at on month [Time Frame: 1 month] [Designated as safety issue: No]Visual analogue scale (VAS) at on month Visual analogue scale (VAS) at 3 months [Time Frame: 3 months] [Designated as safety issue: No]Visual analogue scale (VAS) at 3 months Visual analogue scale (VAS) at 6 months [Time Frame: 6 months] [Designated as safety issue: No]Visual analogue scale (VAS) at 6 months Visual analogue scale (VAS) at 12 months [Time Frame: 12 months] [Designated as safety issue: No]Visual analogue scale (VAS) at 12 months Value of knee injury and osteoarthritis outcome score (Koos) at 1 month [Time Frame: 1 month] [Designated as safety issue: No]Value of knee injury and osteoarthritis outcome score (Koos) at 1 month Value of knee injury and osteoarthritis outcome score (Koos) at 3 month [Time Frame: 3 Months] [Designated as safety issue: No]Value of knee injury and osteoarthritis outcome score (Koos) at 3 month Value of knee injury and osteoarthritis outcome score (Koos) at 6 month [Time Frame: 6 months] [Designated as safety issue: No]Value of knee injury and osteoarthritis outcome score (Koos) at 6 month Value of knee injury and osteoarthritis outcome score (Koos) at 12 months [Time Frame: 12 months] [Designated as safety issue: No]Value of knee injury and osteoarthritis outcome score (Koos) at 12 months Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month [Time Frame: 1 month] [Designated as safety issue: No]Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 3 month [Time Frame: 3 months] [Designated as safety issue: No]Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month [Time Frame: 6 months] [Designated as safety issue: No]Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months [Time Frame: 12 months] [Designated as safety issue: No]Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months SF-36 value at 1 month [Time Frame: 1 month] [Designated as safety issue: No]SF-36 value SF 36 value at 3 months [Time Frame: 3 months] [Designated as safety issue: No]SF 36 value at 3 months SF 36 value at 6 months [Time Frame: 6 months] [Designated as safety issue: No]SF 36 value at 6 months SF 36 value at 12 months [Time Frame: 12 months] [Designated as safety issue: No]SF 36 value at 12 months Euroquol 5D value at 1 month [Time Frame: 1 MOnth] [Designated as safety issue: No]Euroquol 5D value at 1 month Euroquol 5D value at 3 months [Time Frame: 3 months] [Designated as safety issue: No]Euroquol 5D value at 3 months Euroquol 5D value at 6 months [Time Frame: 6 months] [Designated as safety issue: No]Euroquol 5D value at 6 months Euroquol 5D value at 12 months [Time Frame: 12 months] [Designated as safety issue: No]Euroquol 5D value at 12 months Lequesne index at 1 month [Time Frame: 1 month] [Designated as safety issue: No]Lequesne index at 1 month Lequesne index at 3 months [Time Frame: 3 months] [Designated as safety issue: No]Lequesne index at 3 months Lequesne index at 6 months [Time Frame: 6 months] [Designated as safety issue: No]Lequesne index at 6 months Lequesne index at 12 months [Time Frame: 12 months] [Designated as safety issue: No]Lequesne index at 12 months Femorotibial distance at 6 months [Time Frame: 6 months] [Designated as safety issue: No]Femorotibial distance at 6 months Femorotibial distance at 12 months [Time Frame: 12 months] [Designated as safety issue: No]Femorotibial distance at 12 months Baseline MRI WORMS protocol [Time Frame: Prior to the intervention] [Designated as safety issue: No]Prior to the intervention MRI WORMS protocol MRI WORMS protocol score at 6 months [Time Frame: 6 months] [Designated as safety issue: No]MRI WORMS protocol score at 6 months MRI WORMS protocol score at 12 months [Time Frame: 12 months] [Designated as safety issue: No]MRI WORMS protocol score at 12 months
Current Secondary Outcome Measures	Not Provided

Descriptive Information[ + expand ][ + ]

Brief Title	Treatment of Knee Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells
Official Title	Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells
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.
Study Type	Interventional
Study Phase	Phase 1/Phase 2
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Osteoarthritis
Intervention	Drug: Hyaluronic acid Single intraarticular injection of Hyaluronic acid (Hyal One) Other Names: HyalOneBiological: 10 million Bone marrow mesenchimal stem cells 10 million of Bone marrow mesenchimal stem cells Other Names: 10 million Bone marrow mesenchimal stem cellsBiological: 100 million Bone marrow mesenchimal stem cells 100 million of Bone marrow mesenchimal stem cells Other Names: 100 million Bone marrow mesenchimal stem cells
Study Arm (s)	Active Comparator: Hialuronic acid Single intraarticular injection of Hyaluronic acid (Hyal One) Active Comparator: Hyaluronic acid and MSC 10 Single intraarticular injection of Hyaluronic acid (Hyal One) 10 million Bone marrow mesenchimal stem cells Active Comparator: Hyaluronic acid AND MSC 100 Single intraarticular injection of Hyaluronic acid (Hyal One) 100 million Bone marrow mesenchimal stem cells

Recruitment Information[ + expand ][ + ]

Recruitment Status	Active, not recruiting
Estimated Enrollment	30
Estimated Completion Date	November 2014
Estimated Primary Completion Date	November 2014
Eligibility 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.
Gender	Both
Ages	50 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Spain

Administrative Information[ + expand ][ + ]

NCT Number	NCT02123368
Other Study ID Numbers	CMM/ART
Has Data Monitoring Committee	Yes
Information Provided By	Clinica Universidad de Navarra, Universidad de Navarra
Study Sponsor	Clinica Universidad de Navarra, Universidad de Navarra
Collaborators	Not Provided
Investigators	Principal Investigator: José Lamo-Espinosa, MD Clinica Universidad de NavarraStudy Director: Felipe Prosper, MD PhD Clinica Universidad de Navarra
Verification Date	April 2014

Locations[ + expand ][ + ]

Traumatology department. Complejo Hospitalario de Salamanca	Salamanca, Castilla y León, Spain, 37007
Orthopaedic and traumatology department. Clínica Universidad de Navarra	Pamplona, Navarra, Spain, 31008