Treatment of Knee Osteoarthritis With Autologous Mesenchymal Stem Cells (KDD&MSV)

• ClinicalTrials.gov Identifier: NCT01183728
• Recruitment Status: Completed
• First Posted: August 18, 2010
• Results First Posted: January 15, 2015
• Last Update Posted: January 15, 2015
• Sponsor: Red de Terapia Celular
• Collaborators: Fundacion Teknon, Centro Medico Teknon, Barcelona; University of Valladolid; Centro en Red de Medicina Regenerativa de Castilla y Leon; Institut de Terapia Regenerativa Tissular; EGARSAT Suma Intermutual, Barcelona, Spain; Cetir Sant Jordi, S.a..
• Information provided by (Responsible Party): Red de Terapia Celular

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Osteoarthritis, Knee; Knee Degenerative Disease; Knee Osteoarthritis
• Intervention: Other: Autologous bone marrow mesenchymal stem cells (MSV)
• Enrollment: 12

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	MSV Autologous Transplantation
Arm/Group Description	Bone marrow collected from patient will be used for mesenchymal stem cells isolation and expansion under GMP conditions at IBGM-Valladolid (MSV). Autologous MSV implanted in knee by articular injection Autologous bone marrow mesenchymal stem cells (MSV): Bone marrow collection from patient, mesenchymal cells isolation and expansion under GMP conditions following the IBGM-Valladolid protocol (MSV). Autologous MSV implantation by articular injection.
Period Title: Overall Study
Started	12
Completed	12
Not Completed	0

Baseline Characteristics

Arm/Group Title		MSV Autologous Transplantation
Arm/Group Description		Bone marrow collected from patient will be used for mesenchymal stem cells isolation and expansion under GMP conditions at IBGM-Valladolid (MSV). Autologous MSV implanted in knee by articular injection Autologous bone marrow mesenchymal stem cells (MSV): Bone marrow collection from patient, mesenchymal cells isolation and expansion under GMP conditions following the IBGM-Valladolid protocol (MSV). Autologous MSV implantation by articular injection.
Overall Number of Baseline Participants		12
Baseline Analysis Population Description		All included patients met the inclusion criteria and no exclusion criteria.
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	12 participants
>=18 and <=70 years		9
>70 years		3
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants
	Female	4 33.3%
	Male	8 66.7%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Spain	Number Analyzed	12 participants
		12
Number of Participants with Major Surgical History on Treated Knee; Measure Type: Number; Unit of measure: Participants	Number Analyzed	12 participants
With Major Surgical History on Treated Knee		9
Without Major Surgical History on Treated Knee		3
Number of Participants with 4th grade osteoarthritis.; Measure Type: Number; Unit of measure: Participants	Number Analyzed	12 participants
With 4th grade osteoarthritis		5
With 2nd or 3th grade osteoarthritis		7

Outcome Measures

1. Primary Outcome

Title	Feasibility and Safety of the Implementation of MSV in the Treatment of Osteoarthritis of the Knee.
Description	Clinical review, questionaires (VAS - Visual Analogue Scale (a psychometric response scale which can be used for subjective measurements of knee pain), WOMAC - Western Ontario and McMaster Universities Osteoarthritis Index (questionnaire to quantify the pain, stiffness and physical function in patients with osteoarthritis of the knee or hip), Lequesne Index (is a composite measure of pain and disability, with specific self-report questionnaires for knee (osteoarthritis)), SF36 life quality - Short Form 36 (is a questionnaire for the detection of changes in quality of life)). In all cases, the scale was from 0 to 100%. Measurements were performed before cell transplantation (0) and 3, 6, 12 and 24 months afterwards depending on the questionnaire. For VAS, WOMAC and Lequesne, lower values represent a better outcome. For SF-36, higher values represent a better outcome. VAS-DA, VAS for pain associated to daily activities. VAS-SP, VAS for pain associated to sports activities.
Time Frame	0, 3, 6, 12 and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MSV Autologous Transplantation
Arm/Group Description:	Bone marrow collected from patient will be used for mesenchymal stem cells isolation and expansion under GMP conditions at IBGM-Valladolid (MSV). Autologous MSV implanted in knee by articular injection Autologous bone marrow mesenchymal stem cells (MSV): Bone marrow collection from patient, mesenchymal cells isolation and expansion under GMP conditions following the IBGM-Valladolid protocol (MSV). Autologous MSV implantation by articular injection.
Overall Number of Participants Analyzed	12
Mean (Standard Deviation); Unit of Measure: units on a scale
Knee pain VAS-DA. 0 months	46.9 (7.5)
Knee pain VAS-DA. 3 months	25.1 (6.8)
Knee pain VAS-DA. 6 months	24.8 (6.0)
Knee pain VAS-DA. 12 months	15.4 (3.8)
Knee pain VAS-DA. 24 months	15.8 (12.0)
Knee pain VAS-SP. 0 months	56.1 (5.1)
Knee pain VAS-SP. 3 months	29.8 (7.3)
Knee pain VAS-SP. 6 months	28.9 (6.4)
Knee pain VAS-SP. 12 months	18.5 (3.9)
Knee pain VAS-SP. 24 months	18.9 (5.3)
WOMAC - Pain. 0 months	24.2 (4.1)
WOMAC - Pain. 12 months	5.8 (1.6)
WOMAC - Pain. 24 months	11.7 (4.0)
WOMAC - Rigidity. 0 months	10.4 (3.7)
WOMAC - Rigidity. 12 months	5.2 (3.2)
WOMAC - Rigidity. 24 months	8.3 (4.2)
WOMAC - Function loss. 0 months	19.1 (3.8)
WOMAC - Function loss. 12 months	9.4 (3.2)
WOMAC - Function loss. 24 months	12.1 (6.1)
WOMAC - Total. 0 months	19.4 (3.6)
WOMAC - Total. 12 months	8.3 (2.7)
WOMAC - Total. 24 months	11.7 (5.4)
Lequesne. 0 months	45.1 (5.6)
Lequesne. 12 months	14.9 (4.1)
Lequesne. 24 months	13.9 (4.7)
SF-36. Physical Function. Basal	18.8 (22.9)
SF-36. Physical Function. 3 months	21.0 (27.3)
SF-36. Physical Function. 6 months	25.7 (28.4)
SF-36. Physical Function. 12 months	25.1 (22.4)
SF-36. Physical Role. Basal	31.1 (24.5)
SF-36. Physical Role. 3 months	36.9 (26.5)
SF-36. Physical Role. 6 months	38.6 (26.3)
SF-36. Physical Role. 12 months	47.7 (13.7)
SF-36. Bodily Pain. Basal	27.2 (19.6)
SF-36. Bodily Pain. 3 months	25.7 (17.8)
SF-36. Bodily Pain. 6 months	31.8 (22.1)
SF-36. Bodily Pain. 12 months	36.3 (23.8)
SF-36. General Health. Basal	64.8 (16.8)
SF-36. General Health. 3 months	58.5 (17.5)
SF-36. General Health. 6 months	65.2 (22.5)
SF-36. General Health. 12 months	63.3 (20.9)
SF-36. Vitality. Basal	58.3 (23.3)
SF-36. Vitality. 3 months	53.9 (26.1)
SF-36. Vitality. 6 months	56.8 (18.2)
SF-36. Vitality. 12 months	47.7 (13.7)
SF-36. Social Function. Basal	48.8 (22.7)
SF-36. Social Function. 3 months	47.3 (25.0)
SF-36. Social Function. 6 months	53.0 (24.8)
SF-36. Social Function. 12 months	44.2 (18.2)
SF-36. Role Emotional. Basal	54.2 (5.1)
SF-36. Role Emotional. 3 months	53.2 (4.0)
SF-36. Role Emotional. 6 months	53.2 (4.0)
SF-36. Role Emotional. 12 months	50.8 (9.0)
SF-36. Mental Health. Basal	68.1 (18.7)
SF-36. Mental Health. 3 months	61.0 (22.6)
SF-36. Mental Health. 6 months	61.8 (19.5)
SF-36. Mental Health. 12 months	63.3 (22.3)

2. Secondary Outcome

Title	Indication of Efficacy
Description	Clinical exploration, questionaires (VAS, WOMAC, Lequesne Index, SF-36 life quality) at all the periods. To evaluate effectiveness through development of criteria for quantitative MRI (Cartigram) denoting regeneration of articular cartilage at 6, 12 and 24 months after the implantation of MSV. Magnetic Resonance imaging measurements of T2 relaxation (Cartigram) performed at 0, 6 and 12 months to quantify articular cartilage degeneration. The values (in milliseconds) are T1/2 for decay of the T2 MRI signals. Normal values are below 50 ms; values above 50 ms correspond to inflamed cartilage. Mean (SD) are expressed as the percent of values (of a total of 88 measurements) that are between 50 and 90 ms. A value =5 is considered normal (can be attained by chance). Values above 5 are considered pathological. The worst possible is 100.
Time Frame	0, 6, 12, 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MSV Autologous Transplantation
Arm/Group Description:	Bone marrow collected from patient will be used for mesenchymal stem cells isolation and expansion under GMP conditions at IBGM-Valladolid (MSV). Autologous MSV implanted in knee by articular injection Autologous bone marrow mesenchymal stem cells (MSV): Bone marrow collection from patient, mesenchymal cells isolation and expansion under GMP conditions following the IBGM-Valladolid protocol (MSV). Autologous MSV implantation by articular injection.
Overall Number of Participants Analyzed	12
Mean (Standard Deviation); Unit of Measure: percentage of values
MRI T2 mapping. 0 months	19.5 (7.9)
MRI T2 mapping. 6 months	15.4 (7)
MRI T2 mapping. 12 months	14.3 (6.3)
MRI T2 mapping. 24 months	13 (5.8)

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	MSV Autologous Transplantation
Arm/Group Description	Bone marrow collected from patient will be used for mesenchymal stem cells isolation and expansion under GMP conditions at IBGM-Valladolid (MSV). Autologous MSV implanted in knee by articular injection Autologous bone marrow mesenchymal stem cells (MSV): Bone marrow collection from patient, mesenchymal cells isolation and expansion under GMP conditions following the IBGM-Valladolid protocol (MSV). Autologous MSV implantation by articular injection.
All-Cause Mortality
	MSV Autologous Transplantation
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	MSV Autologous Transplantation
	Affected / at Risk (%)	# Events
Total	0/12 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	MSV Autologous Transplantation
	Affected / at Risk (%)	# Events
Total	11/12 (91.67%)
Gastrointestinal disorders
Gluten and lactose intolerance †	1/12 (8.33%)	1
Infections and infestations
Influenza †	1/12 (8.33%)	1
Musculoskeletal and connective tissue disorders
Post implantation pain † [1]	6/12 (50.00%)	8
Joint swelling † [2]	3/12 (25.00%)	3
Unexpected inflammation with joint effusion †	3/12 (25.00%)	3
Contralateral knee pain †	1/12 (8.33%)	1
Lumar pain †	2/12 (16.67%)	4
hamstring tendinitis †	1/12 (8.33%)	1
Surgical and medical procedures
Contralateral knee surgery †	1/12 (8.33%)	1
Dental implant †	1/12 (8.33%)	1
† Indicates events were collected by systematic assessment; [1] between days 1 and 6; [2] Attributable to overload

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Javier García-Sancho
• Organization: Instituto de Biología y Genética Molecular (IBGM)
• Phone: +34 98 318 48 27
• EMail: jgsancho@ibgm.uva.es

Publications of Results:

Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentís J, Sánchez A, García-Sancho J. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation. 2013 Jun 27;95(12):1535-41. doi: 10.1097/TP.0b013e318291a2da.

Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentís J, Sánchez A, García-Sancho J. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-year follow-up results. Transplantation. 2014 Jun 15;97(11):e66-8. doi: 10.1097/TP.0000000000000167.

• Responsible Party: Red de Terapia Celular
• ClinicalTrials.gov Identifier: NCT01183728
• Other Study ID Numbers: TerCel001; Eudra-CT 2009-017405-11 ( Other Grant/Funding Number: RD06/0010/0000 ); Protocol Code ( Registry Identifier: MSV-arthro-2009-01 )
• First Submitted: August 13, 2010
• First Posted: August 18, 2010
• Results First Submitted: December 17, 2014
• Results First Posted: January 15, 2015
• Last Update Posted: January 15, 2015