Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells With Platelet Rich Plasma (CMM-PRGF/ART)

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

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.

Study Overview

• Status: Unknown
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Biological: Platelet Rich plasma (PRGF); Biological: 100 million Bone marrow mesenchimal stem cells

Detailed 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:

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Castilla-León
    • Salamanca, Castilla-León, Spain, 37007
      • Hospital Universitario de Salamanca
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Departamento Cirugía Ortopédica y Traumatología. Clinica Universidad de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Platelet Rich Plasma (PRGF); Platelet Rich plasma (PRGF) 3 intraarticular onjections sepataded by 7 days.	Biological: Platelet Rich plasma (PRGF); 3 injections of PRGF
Active Comparator: BMMSC with Platelet Rich Plasma (PRGF); Single intraarticular injection of 100 million Bone marrow mesenchimal stem cells and three intraarticular injections of plateler Rich Plasma (PRGF) separatede by 7 days.	Biological: Platelet Rich plasma (PRGF); 3 injections of PRGF; Biological: 100 million Bone marrow mesenchimal stem cells; 100 million Bone marrow mesenchimal stem cells with PRGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual analogue scale (VAS) at 3 months	Visual analogue scale (VAS) at 3 months	3 months
Visual analogue scale (VAS) at 6 months	Visual analogue scale (VAS) at 6 months	6 months
Visual analogue scale (VAS) at 12 months	Visual analogue scale (VAS) at 12 months	12 months
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
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
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
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
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
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
Baseline Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC).	Universities Osteoarthritis Index score (WOMAC).	Day 1
Baseline SF-36 value	Baseline SF-36 value	Day 1
Baseline euroquol 5D value	Pretreatment euroquol 5D value	Day 1
Baseline Lequesne index	Prior to the intervention on day 1 Lequesne index	Day 1
Baseline femorotibial distance	Prior to the intervention femoritibial distance on rosenberg x-ray view	Day 1
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)
Visual analogue scale (VAS) at 1 month	Visual analogue scale (VAS) at on month	1 month

Collaborators and Investigators

• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Investigators: Principal Investigator: José Lamo-Espinosa, MD, Clinica Universidad de Navarra; Study Director: Felipe Prosper, MD, PhD, Clinica Universidad de Navarra; Principal Investigator: Juan Blanco, MD; PhD, Complejo Universitario de Salamanca

Publications and helpful links

General Publications

• Lamo-Espinosa JM, Blanco JF, Sanchez M, Moreno V, Granero-Molto F, Sanchez-Guijo F, Crespo-Cullel I, Mora G, San Vicente DD, Pompei-Fernandez O, Aquerreta JD, Nunez-Cordoba JM, Vitoria Sola M, Valenti-Azcarate A, Andreu EJ, Del Consuelo Del Canizo M, Valenti-Nin JR, Prosper F. Phase II multicenter randomized controlled clinical trial on the efficacy of intra-articular injection of autologous bone marrow mesenchymal stem cells with platelet rich plasma for the treatment of knee osteoarthritis. J Transl Med. 2020 Sep 18;18(1):356. doi: 10.1186/s12967-020-02530-6.

Helpful Links

• University clinic of navarre trial information

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: July 18, 2014
• First Submitted That Met QC Criteria: February 17, 2015
• First Posted (Estimate): February 18, 2015

Study Record Updates

• Last Update Posted (Actual): October 24, 2017
• Last Update Submitted That Met QC Criteria: October 23, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Osteoarthritis; Knee Osteoarthritis; Mesenchimal stem cell
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: CMM-PRGF/ART; 2011-006036-23 (EudraCT Number)