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Trial record 7 of 56 for:    stem cell arthritis AND bone marrow

Treatment of Knee Osteoarthritis With Allogenic Mesenchymal Stem Cells (MSV_allo)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01586312
Recruitment Status : Completed
First Posted : April 26, 2012
Results First Posted : November 6, 2014
Last Update Posted : October 16, 2015
Sponsor:
Collaborators:
University of Valladolid
Sanidad de Castilla y Leon (SACYL)
Centro Medico Teknon
Information provided by (Responsible Party):
Red de Terapia Celular

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Osteoarthritis, Knee
Arthritis of Knee
Knee Osteoarthritis
Interventions Other: Allogenic mesenchymal stromal cells injection
Drug: Hyaluronic Acid
Enrollment 30
Recruitment Details 30 patients were included between 26/Jul/2012 (Pat. 01) and12/Dic/2012 (Pat. 30).
Pre-assignment Details All patients fulfilled the selection criteria, were randomized and received the assigned medication.
Arm/Group Title Allogenic Mesenchymal Stromal Cells Hyaluronic Acid (Durolane)
Hide Arm/Group Description

Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intraarticular injection of 40 millions MSC.

Injection of Mesenchymal Stromal Cells: Mesenchymal stem cells prepared from bone marrow of healthy donors and expanded for 3-4 weeks according to our procedure described in PEI Num. 10-134, authorized by the Spanish Medicine Agency

Intraarticular injection of hyaluronic acid (60 mg)

Hyaluronic Acid: Intra-articular injection of 60 mg of hyaluronic acid (Durolane) in a single injection (3 ml)

Period Title: Overall Study
Started 15 15
Completed 15 15
Not Completed 0 0
Arm/Group Title Allogenic Mesenchymal Stromal Cells Hyaluronic Acid (Durolane) Total
Hide Arm/Group Description

Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intraarticular injection of 40 millions MSC.

Injection of Mesenchymal Stromal Cells: Mesenchymal stem cells prepared from bone marrow of healthy donors and expanded for 3-4 weeks according to our procedure described in PEI Num. 10-134, authorized by the Spanish Medicine Agency

Intraarticular injection of hyaluronic acid (60 mg)

Hyaluronic Acid: Intra-articular injection of 60 mg of hyaluronic acid (Durolane) in a single injection (3 ml)

Total of all reporting groups
Overall Number of Baseline Participants 15 15 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 15 participants 30 participants
56.60  (9.57) 57.33  (9.41) 56.97  (9.33)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 30 participants
Female
7
  46.7%
10
  66.7%
17
  56.7%
Male
8
  53.3%
5
  33.3%
13
  43.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 30 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
15
 100.0%
15
 100.0%
30
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Spain Number Analyzed 15 participants 15 participants 30 participants
15 15 30
1.Primary Outcome
Title Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Hide Description Adverse events reported. Clinical review and questionaires for pain, disability and quality of life at 0, 3, 6 and 12 months
Time Frame Up to one year
Hide Outcome Measure Data
Hide Analysis Population Description

Efficacy evaluable patients (EEP): A patient has been considered evaluable whenever it has undergone the specified interventions (injection of hyaluronic acid or allogeneic MSC).

and

Safety population (SP): The population that includes all evaluable patients who have undergone one of the two study treatments.

Arm/Group Title Allogenic Mesenchymal Stromal Cells Hyaluronic Acid (Durolane)
Hide Arm/Group Description:

Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intraarticular injection of 40 millions MSC.

Injection of Mesenchymal Stromal Cells: Mesenchymal stem cells prepared from bone marrow of healthy donors and expanded for 3-4 weeks according to our procedure described in PEI Num. 10-134, authorized by the Spanish Medicine Agency

Intraarticular injection of hyaluronic acid (60 mg)

Hyaluronic Acid: Intra-articular injection of 60 mg of hyaluronic acid (Durolane) in a single injection (3 ml)

Overall Number of Participants Analyzed 15 15
Measure Type: Number
Unit of Measure: participants
14 13
2.Secondary Outcome
Title Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores)
Hide Description

Clinical review, questionaires for pain, disability and quality of life at 0, 3, 6 and 12 months.

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.

SF-12 (Short Form 12, an abbreviated form of SF36) is a questionnaire for the detection of changes in quality of life.

The visual analogue scale (VAS) is a psychometric response scale which can be used for subjective measurements of knee pain.

LEQUESNE algofunctional index: is a composite measure of pain and disability, with specific self-report questionnaires for knee (osteoarthritis).

All the scale ranges ranges (minimum and maximum scores) are between 0 and 100%.

Values are given in differences from baseline (usually negative values). More negative values show more improvement on both scales.

Time Frame up to one year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Allogenic Mesenchymal Stromal Cells Hyaluronic Acid (Durolane)
Hide Arm/Group Description:

Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intraarticular injection of 40 millions MSC.

Injection of Mesenchymal Stromal Cells: Mesenchymal stem cells prepared from bone marrow of healthy donors and expanded for 3-4 weeks according to our procedure described in PEI Num. 10-134, authorized by the Spanish Medicine Agency

Intraarticular injection of hyaluronic acid (60 mg)

Hyaluronic Acid: Intra-articular injection of 60 mg of hyaluronic acid (Durolane) in a single injection (3 ml)

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: units on a scale
WOMAC11_Changes from Basal - General 3 months -8.48  (22.6) -4.52  (17.4)
WOMAC11_Changes from Basal - General 6 months -13.03  (18.2) -5.47  (15.9)
WOMAC11_Changes from Basal - General 12 months -13.47  (22.8) -4.10  (18.4)
WOMAC11_Changes from Basal - Dificulty 3 months -8.51  (22.8) -6.46  (18.7)
WOMAC11_Changes from Basal - Dificulty 6 months -14.53  (19.8) -6.97  (20.5)
WOMAC11_Changes from Basal - Dificulty 12 months -12.59  (23.1) -4.26  (21.3)
WOMAC11_Changes from Basal - Stiffness 3 months -4.77  (30.5) -1.93  (25.2)
WOMAC11_Changes from Basal - Stiffness 6 months -3.17  (23.8) -2.87  (23.6)
WOMAC11_Changes from Basal - Stiffness 12 months -10.67  (31.1) -4.50  (29.5)
WOMAC11_Changes from Basal - Pain 3 months -10.01  (23.7) -4.27  (17.2)
WOMAC11_Changes from Basal - Pain 6 months -13.02  (19.0) -5.97  (12.1)
WOMAC11_Changes from Basal - Pain 12 months -16.30  (23) -6.36  (15.8)
SF-12_Changes from Basal - General Health 3 months 0.12  (22.5) 0.39  (16.2)
SF-12_Changes from Basal - General Health 6 months 10.64  (22.8) 2.11  (21.2)
SF-12_Changes from Basal - General Health 12 month 5.24  (27.9) 2.51  (21.1)
SF-12_Changes from Basal - Physical function 3 m 10.00  (36.4) 18.33  (30.6)
SF-12_Changes from Basal - Physical function 6 m 13.33  (26.5) 11.67  (32.6)
SF-12_Changes from Basal - Physical function 12 m 21.67  (22.9) 20.00  (30.2)
SF-12_Changes from Basal - Physical rol 3 months 2.50  (21.2) 4.17  (31.2)
SF-12_Changes from Basal - Physical rol 6 months 6.67  (38.9) 9.17  (29.7)
SF-12_Changes from Basal - Physical rol 12 months 5.00  (34.0) 6.67  (30.6)
SF-12_Changes from Basal - Emotional rol 3 months -1.67  (22.6) -5.83  (24.5)
SF-12_Changes from Basal - Emotional rol 6 months 5.83  (33.0) 1.67  (15.6)
SF-12_Changes from Basal - Emotional rol 12 months 0.00  (31.0) 0.83  (18.0)
SF-12_Changes from Basal - Body pain 3 months 10.0  (26.4) 5.00  (28.7)
SF-12_Changes from Basal - Body pain 6 months 15.00  (28.0) 11.67  (26.5)
SF-12_Changes from Basal - Body pain 12 months 13.33  (36.4) 13.33  (24.8)
SF-12_Changes from Basal - Mental Health 3 months -5.83  (24.5) 3.33  (19.7)
SF-12_Changes from Basal - Mental Health 6 months 3.33  (25.2) 3.33  (19.7)
SF-12_Changes from Basal - Mental Health 12 months 0.00  (14.2) 5.00  (18.8)
SF-12_Changes from Basal - Vitality 3 months -6.67  (37.2) 1.67  (25.8)
SF-12_Changes from Basal - Vitality 6 months -1.67  (33.4) 1.67  (25.8)
SF-12_Changes from Basal - Vitality 12 months -8.33  (36.2) -6.67  (24.0)
SF-12_Changes from Basal - Social function 3 mo -1.67  (27.5) -1.67  (27.5)
SF-12_Changes from Basal - Social function 6 mo 6.67  (27.5) -6.67  (29.1)
SF-12_Changes from Basal - Social function 12 mo 6.67  (29.1) 0.00  (26.7)
SF-12_Changes from Basal - Physical Health 3 mo 3.44  (7.8) 3.71  (7.6)
SF-12_Changes from Basal - Physical Health 6 mo 4.51  (7.0) 3.76  (9.3)
SF-12_Changes from Basal - Physical Health 12 mo 5.42  (9.3) 4.59  (9.3)
SF-12_Changes from Basal - Mental Health 3 mo -3.56  (10.5) -1.99  (8.9)
SF-12_Changes from Basal - Mental Health 6 mo 0.44  (11.7) -1.09  (7.0)
SF-12_Changes from Basal - Mental Health 12 mo -2.41  (8.2) -1.56  (9.1)
VAS_Changes from Basal - 3 months -13.67  (30.7) -7.53  (23.6)
VAS_Changes from Basal - 6 months -20.67  (29.3) -11.93  (20.6)
VAS_Changes from Basal - 12 months -21.20  (28.5) -13.07  (21.6)
LEQUESNE_Changes from Basal - 3 months -3.63  (12.4) -5.18  (12.8)
LEQUESNE_Changes from Basal - 6 months -13.95  (10.8) -5.46  (13.4)
LEQUESNE_Changes from Basal - 12 months -8.76  (12.4) -3.13  (12.6)
3.Secondary Outcome
Title Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram)
Hide Description

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 number of values (of a total of 88 measurements) that are between 50 and 90 ms. A value =<4.4 is considered normal (can be attained by chance). Values above 4.4 are considered pathological. The worst possible is 88.

Time Frame up to one year
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy endpoint analysis will be based on all patients who have not committed major protocol violations, and have at least one assessment of efficacy of the end graft. 3 patients of the allogenic MSC treatment group were excluded from this analysis because of incomplete measurements.
Arm/Group Title Allogenic Mesenchymal Stromal Cells Hyaluronic Acid (Durolane)
Hide Arm/Group Description:

Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intraarticular injection of 40 millions MSC.

Injection of Mesenchymal Stromal Cells: Mesenchymal stem cells prepared from bone marrow of healthy donors and expanded for 3-4 weeks according to our procedure described in PEI Num. 10-134, authorized by the Spanish Medicine Agency

Intraarticular injection of hyaluronic acid (60 mg)

Hyaluronic Acid: Intra-articular injection of 60 mg of hyaluronic acid (Durolane) in a single injection (3 ml)

Overall Number of Participants Analyzed 12 15
Mean (Standard Deviation)
Unit of Measure: number of values (range 0-88)
MRI. Nº of values between 50-90 per visit. 0 12.33  (3.5) 13.53  (5.7)
MRI. Nº of values between 50-90 per visit. 6 9.33  (4.5) 11.73  (7.5)
MRI.Nº of values between 50-90 per visit.12. 8.25  (5.6) 10.73  (5.5)
MRI. Change of Nº of measurements. 6 -3.00  (2.5) -1.80  (5.8)
MRI. Change of Nº of measurements.12 -4.08  (6.0) -2.80  (4.1)
Time Frame 1 year
Adverse Event Reporting Description All patients completed the study successfully. The mean duration of the patients in the study was 12.4 (± 0.6) months, 12.5 (± 0.8) months in the MSV group and 12.4 (± 0.3) months in the hyaluronic acid group.
 
Arm/Group Title Allogenic Mesenchymal Stromal Cells Hyaluronic Acid (Durolane)
Hide Arm/Group Description

Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intraarticular injection of 40 millions MSC.

Injection of Mesenchymal Stromal Cells: Mesenchymal stem cells prepared from bone marrow of healthy donors and expanded for 3-4 weeks according to our procedure described in PEI Num. 10-134, authorized by the Spanish Medicine Agency

Intraarticular injection of hyaluronic acid (60 mg)

Hyaluronic Acid: Intra-articular injection of 60 mg of hyaluronic acid (Durolane) in a single injection (3 ml)

All-Cause Mortality
Allogenic Mesenchymal Stromal Cells Hyaluronic Acid (Durolane)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Allogenic Mesenchymal Stromal Cells Hyaluronic Acid (Durolane)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/15 (0.00%)      0/15 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Allogenic Mesenchymal Stromal Cells Hyaluronic Acid (Durolane)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/15 (93.33%)      13/15 (86.67%)    
Endocrine disorders     
Hyperthyroidism  1  0/15 (0.00%)  0 1/15 (6.67%)  1
Eye disorders     
Corneal erosion / Blepharitis  1  0/15 (0.00%)  0 1/15 (6.67%)  1
Gastrointestinal disorders     
Dental pain  1  0/15 (0.00%)  0 2/15 (13.33%)  2
General disorders     
Leak  1  1/15 (6.67%)  1 0/15 (0.00%)  0
Immune system disorders     
Hypersensitivity  1  2/15 (13.33%)  2 0/15 (0.00%)  0
Infections and infestations     
Ear infection  1  3/15 (20.00%)  3 2/15 (13.33%)  3
Nasofaringitis  1  1/15 (6.67%)  1 0/15 (0.00%)  0
Pneumonia  1  1/15 (6.67%)  1 1/15 (6.67%)  2
Rinitis  1  1/15 (6.67%)  1 0/15 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Artralgia  1  6/15 (40.00%)  9 7/15 (46.67%)  9
Joint Effusion  1  2/15 (13.33%)  3 3/15 (20.00%)  4
Back pain  1  2/15 (13.33%)  2 2/15 (13.33%)  2
Musculoskeletal pain  1  0/15 (0.00%)  0 1/15 (6.67%)  1
Artralgia/Artritis  1  3/15 (20.00%)  3 1/15 (6.67%)  1
Arthralgia/Effusion  1  0/15 (0.00%)  0 1/15 (6.67%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  0/15 (0.00%)  0 1/15 (6.67%)  1
Neoplasia  1  0/15 (0.00%)  0 1/15 (6.67%)  1
Nervous system disorders     
Amnesia  1  1/15 (6.67%)  1 2/15 (13.33%)  12
Migraine  1  0/15 (0.00%)  0 1/15 (6.67%)  1
Drowsiness  1  1/15 (6.67%)  1 0/15 (0.00%)  0
Psychiatric disorders     
Depression  1  1/15 (6.67%)  1 0/15 (0.00%)  0
Nervousness  1  0/15 (0.00%)  0 1/15 (6.67%)  1
Reproductive system and breast disorders     
Amenorrhea  1  1/15 (6.67%)  1 0/15 (0.00%)  0
Testicular pain  1  0/15 (0.00%)  0 1/15 (6.67%)  1
Premature menopause  1  1/15 (6.67%)  1 0/15 (0.00%)  0
Menorrhagia  1  0/15 (0.00%)  0 1/15 (6.67%)  2
Skin and subcutaneous tissue disorders     
Allergic dermatitis  1  0/15 (0.00%)  0 1/15 (6.67%)  1
Surgical and medical procedures     
Dental implant  1  0/15 (0.00%)  0 2/15 (13.33%)  2
Vascular disorders     
Hypertension  1  0/15 (0.00%)  0 1/15 (6.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor must review results communications prior to public release.
Results Point of Contact
Name/Title: Professor Javier Garcia-Sancho
Organization: Instituto de Biología y Genética Molecular (IBGM)
Phone: 34 983 423 084
Responsible Party: Red de Terapia Celular
ClinicalTrials.gov Identifier: NCT01586312     History of Changes
Other Study ID Numbers: TerCel004
2011-005321-51 ( EudraCT Number )
EC11-309 ( Other Grant/Funding Number: Spanish Ministry of Health, Independent Clinical Investigatio )
MSV_allo ( Registry Identifier: Protocol code )
First Submitted: April 23, 2012
First Posted: April 26, 2012
Results First Submitted: September 24, 2014
Results First Posted: November 6, 2014
Last Update Posted: October 16, 2015