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

Osteoarthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02123368
• Other study ID #: CMM/ART
• Secondary ID: 2009-017624-72
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 12, 2013
• Last updated: October 23, 2017
• Start date: May 2012
• Est. completion date: February 2015

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) 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteoarthritis

Intervention

Drug:
• Hyaluronic acid
Single intraarticular injection of Hyaluronic acid (Hyal One)

Biological:
• 10 million Bone marrow mesenchimal stem cells
10 million of Bone marrow mesenchimal stem cells
• 100 million Bone marrow mesenchimal stem cells
100 million of Bone marrow mesenchimal stem cells

Locations

Country	Name	City	State
Spain	Orthopaedic and traumatology department. Clínica Universidad de Navarra	Pamplona	Navarra
Spain	Traumatology department. Complejo Hospitalario de Salamanca	Salamanca	Castilla y 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)	prior to the initial dose on 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).	Prior to the intervention on day 1
Primary	Baseline Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC).	Prior to the intervention on day 1 Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC).	Prior to the intervention on day 1
Primary	Baseline SF-36 value	Prior to the intervention on day 1 SF-36 value	Prior to the intervention on day 1
Primary	Baseline euroquol 5D value	Pretreatment euroquol 5D value	Prior to the intervention on day 1
Primary	Baseline Lequesne index	Prior to the intervention on day 1 Lequesne index	Prior to the intervention on day 1
Primary	Baseline femorotibial distance	Prior to the intervention femoritibial distance on rosenberg x-ray view	Prior to the intervention
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	During the follow up	Follow up
Primary	Visual analogue scale (VAS) at on 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
Primary	Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month	Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month	1 month
Primary	Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 3 month	Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month	3 months
Primary	Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month	Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month	6 months
Primary	Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months	Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months	12 months
Primary	SF-36 value at 1 month	SF-36 value	1 month
Primary	SF 36 value at 3 months	SF 36 value at 3 months	3 months
Primary	SF 36 value at 6 months	SF 36 value at 6 months	6 months
Primary	SF 36 value at 12 months	SF 36 value at 12 months	12 months
Primary	Euroquol 5D value at 1 month	Euroquol 5D value at 1 month	1 MOnth
Primary	Euroquol 5D value at 3 months	Euroquol 5D value at 3 months	3 months
Primary	Euroquol 5D value at 6 months	Euroquol 5D value at 6 months	6 months
Primary	Euroquol 5D value at 12 months	Euroquol 5D value at 12 months	12 months
Primary	Lequesne index at 1 month	Lequesne index at 1 month	1 month
Primary	Lequesne index at 3 months	Lequesne index at 3 months	3 months
Primary	Lequesne index at 6 months	Lequesne index at 6 months	6 months
Primary	Lequesne index at 12 months	Lequesne index at 12 months	12 months
Primary	Femorotibial distance at 6 months	Femorotibial distance at 6 months	6 months
Primary	Femorotibial distance at 12 months	Femorotibial distance at 12 months	12 months
Primary	Baseline MRI WORMS protocol	Prior to the intervention MRI WORMS protocol	Prior to the intervention
Primary	MRI WORMS protocol score at 6 months	MRI WORMS protocol score at 6 months	6 months
Primary	MRI WORMS protocol score at 12 months	MRI WORMS protocol score at 12 months	12 months

External Links

•   University clinic of navarre trial information