Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells With Platelet Rich Plasma

Knee Osteoarthritis Clinical Trial

— CMM-PRGF/ART  

Official title:

Phase I/II. Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells With Platelet Rich Plasma(PRGF)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02365142
• Other study ID #: CMM-PRGF/ART
• Secondary ID: 2011-006036-23
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: July 18, 2014
• Last updated: October 23, 2017
• Start date: June 2014
• Est. completion date: June 2018

Study information

• Verified date: October 2017
• Source: Clinica Universidad de Navarra, Universidad de Navarra
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Patients and methods

Clinical trial phase I- II, randomized , multicenter , with two treatment arms and 19 patients for each group. The investigators compare the intraarticular injection of against the administration of two different doses of mesenchymal stem cells with hialuronic acid according to the following scheme:

1. Group A: 3 intra-articular injections of platelet rich plasma (PRGF®) separated by 7 days.

2. Group B: 3 intra-articular injections of platelet richa plasma (PRGF®) separated by 7 days and one with Mesenchimal stems cells. 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 of platelet richa plasma (PRGF®). The treatment is completed with 2 more injection of platelet richa plasma (PRGF®) separeted by one week.

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 and 12 months from treatment): Femorotibial space.

• Radiographic using MRI (baseline and 12 months from treatment): by assessing the number location of the lesions , cartilage thickness , signal intensity , subchondral bone alteration , volume and WORMS and dGEMRIC protocols.

Description:

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

Patients and methods

Clinical trial phase I- II, randomized , multicenter , with two treatment arms and 19 patients for each group. The investigators compare the intraarticular injection of against the administration of two different doses of mesenchymal stem cells with hialuronic acid according to the following scheme:

1. Group A: 3 intra-articular injections of platelet richa plasma (PRGF®) separated by 7 days.

2. Group B: 3 intra-articular injections of platelet richa plasma (PRGF®) separated by 7 days and one with Mesenchimal stem cell. 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 of platelet richa plasma (PRGF®). The treatment is completed with 2 more injection of platelet richa plasma (PRGF®) separeted by one week.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 38
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• Males and females between 40 and 80 year old

• Bad results with previous hyaluronic acid injection

• 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

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Biological:
• 100 million Bone marrow mesenchimal stem cells
100 million Bone marrow mesenchimal stem cells with PRGF
• Platelet Rich plasma (PRGF)
3 injections of PRGF

Locations

Country	Name	City	State
Spain	Departamento Cirugía Ortopédica y Traumatología. Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario de Salamanca	Salamanca	Castilla-León

Sponsors (1)

Lead Sponsor	Collaborator
Clinica Universidad de Navarra, Universidad de Navarra

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Baseline Visual analogue scale (VAS) Baseline Visual analogue scale (VAS)	Baseline Visual analogue scale (VAS) prior to the initial dose on day 1	Day 1
Primary	Baseline value of knee injury and osteoarthritis outcome score (Koos).	Prior to the intervention on day 1 value of knee injury and osteoarthritis outcome score (Koos).	Day 1
Primary	Baseline Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC).	Universities Osteoarthritis Index score (WOMAC).	Day 1
Primary	Baseline SF-36 value	Baseline SF-36 value	Day 1
Primary	Baseline euroquol 5D value	Pretreatment euroquol 5D value	Day 1
Primary	Baseline Lequesne index	Prior to the intervention on day 1 Lequesne index	Day 1
Primary	Baseline femorotibial distance	Prior to the intervention femoritibial distance on rosenberg x-ray view	Day 1
Primary	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	Participants with Serious and Non-Serious Adverse Events Number of Participants with Serious and Non-Serious Adverse Events During the follow up	Follow up (up to 12 months)
Primary	Visual analogue scale (VAS) at 1 month	Visual analogue scale (VAS) at on month	1 month
Primary	Visual analogue scale (VAS) at 3 months	Visual analogue scale (VAS) at 3 months	3 months
Primary	Visual analogue scale (VAS) at 6 months	Visual analogue scale (VAS) at 6 months	6 months
Primary	Visual analogue scale (VAS) at 12 months	Visual analogue scale (VAS) at 12 months	12 months
Primary	Value of knee injury and osteoarthritis outcome score (Koos) at 1 month	Value of knee injury and osteoarthritis outcome score (Koos) at 1 month	1 month
Primary	Value of knee injury and osteoarthritis outcome score (Koos) at 3 month	Value of knee injury and osteoarthritis outcome score (Koos) at 3 month	3 Months
Primary	Value of knee injury and osteoarthritis outcome score (Koos) at 6 month	Value of knee injury and osteoarthritis outcome score (Koos) at 6 month	6 months
Primary	Value of knee injury and osteoarthritis outcome score (Koos) at 12 months	Value of knee injury and osteoarthritis outcome score (Koos) at 12 months	12 months

External Links

•   University clinic of navarre trial information