Clinical trial NCT02123368: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Osteoarthritis
Keywords: Osteoarthritis
Mesenchimal stem cell
Knee
Lead sponsor: Clinica Universidad de Navarra, Universidad de Navarra
Sponsor class: OTHER
First posted: 2014-04-25
Enrollment: 30
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Baseline Visual analogue scale (VAS)
timeFrame: prior to the initial dose on day 1
measure: Baseline value of knee injury and osteoarthritis outcome score (Koos).
timeFrame: Prior to the intervention on day 1
measure: Baseline Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC).
timeFrame: Prior to the intervention on day 1
measure: Baseline SF-36 value
timeFrame: Prior to the intervention on day 1
measure: Baseline euroquol 5D value
timeFrame: Prior to the intervention on day 1
measure: Baseline Lequesne index
timeFrame: Prior to the intervention on day 1
measure: Baseline femorotibial distance
timeFrame: Prior to the intervention
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
measure: Visual analogue scale (VAS) at on 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
measure: Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month
timeFrame: 1 month
measure: Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 3 month
timeFrame: 3 months
measure: Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month
timeFrame: 6 months
measure: Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months
timeFrame: 12 months
measure: SF-36 value at 1 month
timeFrame: 1 month
measure: SF 36 value at 3 months
timeFrame: 3 months
measure: SF 36 value at 6 months
timeFrame: 6 months
measure: SF 36 value at 12 months
timeFrame: 12 months
measure: Euroquol 5D value at 1 month
timeFrame: 1 MOnth
measure: Euroquol 5D value at 3 months
timeFrame: 3 months
measure: Euroquol 5D value at 6 months
timeFrame: 6 months
measure: Euroquol 5D value at 12 months
timeFrame: 12 months
measure: Lequesne index at 1 month
timeFrame: 1 month
measure: Lequesne index at 3 months
timeFrame: 3 months
measure: Lequesne index at 6 months
timeFrame: 6 months
measure: Lequesne index at 12 months
timeFrame: 12 months
measure: Femorotibial distance at 6 months
timeFrame: 6 months
measure: Femorotibial distance at 12 months
timeFrame: 12 months
measure: Baseline MRI WORMS protocol
timeFrame: Prior to the intervention
measure: MRI WORMS protocol score at 6 months
timeFrame: 6 months
measure: MRI WORMS protocol score at 12 months
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Salamanca
country: Spain
facility: Traumatology department. Complejo Hospitalario de Salamanca
state: Castilla y León
city: Pamplona
country: Spain
facility: Orthopaedic and traumatology department. Clínica Universidad de Navarra
state: Navarra
Study officials:
affiliation: Clinica Universidad de Navarra
name: José Lamo-Espinosa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinica Universidad de Navarra
name: Felipe Prosper, MD PhD
role: STUDY_DIRECTOR
affiliation: University of Salamanca
name: Juan Blanco, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lamo-Espinosa JM, Prosper F, Blanco JF, Sanchez-Guijo F, Alberca M, Garcia V, Gonzalez-Vallinas M, Garcia-Sancho J. Long-term efficacy of autologous bone marrow mesenchymal stromal cells for treatment of knee osteoarthritis. J Transl Med. 2021 Dec 11;19(1):506. doi: 10.1186/s12967-021-03160-2.
citation: Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Molto F, Nunez-Cordoba JM, Lopez-Elio S, Andreu E, Sanchez-Guijo F, Aquerreta JD, Bondia JM, Valenti-Azcarate A, Del Consuelo Del Canizo M, Villaron EM, Valenti-Nin JR, Prosper F. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II). J Transl Med. 2018 Jul 31;16(1):213. doi: 10.1186/s12967-018-1591-7.
citation: Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Molto F, Nunez-Cordoba JM, Sanchez-Echenique C, Bondia JM, Aquerreta JD, Andreu EJ, Ornilla E, Villaron EM, Valenti-Azcarate A, Sanchez-Guijo F, Del Canizo MC, Valenti-Nin JR, Prosper F. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II). J Transl Med. 2016 Aug 26;14(1):246. doi: 10.1186/s12967-016-0998-2.