Clinical trial NCT02365142: Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells With Platelet Rich Plasma
Official title: Phase I/II. Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells With Platelet Rich Plasma(PRGF)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Knee Osteoarthritis
Keywords: Knee Osteoarthritis
Mesenchimal stem cell
Osteoarthritis
Lead sponsor: Clinica Universidad de Navarra, Universidad de Navarra
Sponsor class: OTHER
First posted: 2015-02-18
Enrollment: 38
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

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:

Eligibility criteria: 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

Primary outcomes:
measure: Baseline Visual analogue scale (VAS) Baseline Visual analogue scale (VAS)
timeFrame: Day 1
measure: Baseline value of knee injury and osteoarthritis outcome score (Koos).
timeFrame: Day 1
measure: Baseline Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC).
timeFrame: Day 1
measure: Baseline SF-36 value
timeFrame: Day 1
measure: Baseline euroquol 5D value
timeFrame: Day 1
measure: Baseline Lequesne index
timeFrame: Day 1
measure: Baseline femorotibial distance
timeFrame: Day 1
measure: 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
timeFrame: Follow up (up to 12 months)
measure: Visual analogue scale (VAS) at 1 month
timeFrame: 1 month
measure: Visual analogue scale (VAS) at 3 months
timeFrame: 3 months
measure: Visual analogue scale (VAS) at 6 months
timeFrame: 6 months
measure: Visual analogue scale (VAS) at 12 months
timeFrame: 12 months
measure: Value of knee injury and osteoarthritis outcome score (Koos) at 1 month
timeFrame: 1 month
measure: Value of knee injury and osteoarthritis outcome score (Koos) at 3 month
timeFrame: 3 Months
measure: Value of knee injury and osteoarthritis outcome score (Koos) at 6 month
timeFrame: 6 months
measure: Value of knee injury and osteoarthritis outcome score (Koos) at 12 months
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
state: Castilla-León
city: Pamplona
country: Spain
facility: Departamento Cirugía Ortopédica y Traumatología. Clinica Universidad de Navarra
state: Navarra
Study officials:
affiliation: Clinica Universidad de Navarra
name: José Lamo-Espinosa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clínica Universidad de Navarra
name: Felipe Prosper, MD, PhD
role: STUDY_DIRECTOR
affiliation: Complejo Universitario de Salamanca
name: Juan Blanco, MD; PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.