Trial Outcomes & Findings for Treatment of Degenerative Disc Disease With Allogenic Mesenchymal Stem Cells (MSV) (NCT NCT01860417)

NCT ID: NCT01860417

Last Updated: 2024-04-29

Results Overview

Change in the composite variable, which includes pain and disability 1 year after intervention, was plotted as a function of the initial pain score or disability index. Results for the relief of lumbar pain and Oswestry disability index were all included for both, control and cell-treated patients. The scores obtained from this analysis (slope of the plot) range from 0 to 1, with higher scores meaning a better outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 24 participants
• Primary outcome timeframe: Change since the baseline (before intervention) up to the end of the follow-up period, 12 months after the intervention
• Results posted on: 2024-04-29

Participant Flow

Recruitment was performed between June 2013 and March 2014. Date of Last visit last patient was December 2015. The study was conducted in only one center in Spain.

Participant milestones

Measure	Allogenic Bone Marrow Mesenquimal Cells Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Overall Study STARTED	12	12
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment of Degenerative Disc Disease With Allogenic Mesenchymal Stem Cells (MSV)

Baseline characteristics by cohort

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	40.5 years n=5 Participants	37 years n=7 Participants	38 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Spain	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Weight	72 Kg n=5 Participants	74 Kg n=7 Participants	72.5 Kg n=5 Participants
Height	166.5 cm n=5 Participants	176.5 cm n=7 Participants	172 cm n=5 Participants
Body mass index	25.5 kg/m^2 n=5 Participants	24.0 kg/m^2 n=7 Participants	24.5 kg/m^2 n=5 Participants
Participants with Previous Treatment	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Visual Analogue Scale	73.5 units on a scale n=5 Participants	72.5 units on a scale n=7 Participants	73 units on a scale n=5 Participants
Oswestry Disability Index	26 units on a scale n=5 Participants	22 units on a scale n=7 Participants	24 units on a scale n=5 Participants
SF-12 Physical Component	38 units on a scale n=5 Participants	42.5 units on a scale n=7 Participants	38.5 units on a scale n=5 Participants
SF-12 Mental Component	50 units on a scale n=5 Participants	50 units on a scale n=7 Participants	50 units on a scale n=5 Participants
Pfirrmann grading system Gr II	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Pfirrmann grading system Gr III	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Pfirrmann grading system Gr IV	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Change since the baseline (before intervention) up to the end of the follow-up period, 12 months after the intervention

Change in the composite variable, which includes pain and disability 1 year after intervention, was plotted as a function of the initial pain score or disability index. Results for the relief of lumbar pain and Oswestry disability index were all included for both, control and cell-treated patients. The scores obtained from this analysis (slope of the plot) range from 0 to 1, with higher scores meaning a better outcome.

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Pain and Disability Evaluation	0.28 scores from 0 to 1 Standard Error 0.07	0.15 scores from 0 to 1 Standard Error 0.1

SECONDARY outcome

Timeframe: At 12 months from 6 months after the intervention

Ratio discs density: Discs density at 12 months divided by discs density at 6 months after transplantation.

To homogenize the results of different patients, the water content values of the affected discs were normalized to the values obtained from the healthy discs in the same individual; for these purposes, the density of the affected segments was divided by the average value of the healthy discs. Finally, the value after the treatment was divided by the baseline value.

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Evaluation of Affected Disc(s) by Quantitative MRI Ratio 12/6months	0.22 ratio Standard Error 0.11	0.06 ratio Standard Error 0.08

SECONDARY outcome

Timeframe: At 6 months after the intervention

Measurement of the amount of fluid in the disc. To homogenize the results of different patients, the water content values of the affected discs were normalized to the values obtained from the healthy discs in the same individual; for these purposes, the density of the affected segments was divided by the average value of the healthy discs. Finally, the value after the treatment was divided by the baseline value.

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Evaluation of Affected Disc(s) by Quantitative Magnetic Resonance Imaging (RMI): Density at 6 Months	0.42 ratio Standard Error 0.05	0.51 ratio Standard Error 0.05

SECONDARY outcome

Timeframe: At 12 months after the intervention

Measurement of the amount of fluid in the disc. To homogenize the results of different patients, the water content values of the affected discs were normalized to the values obtained from the healthy discs in the same individual; for these purposes, the density of the affected segments was divided by the average value of the healthy discs. Finally, the value after the treatment was divided by the baseline value.

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Evaluation of Affected Disc(s) by Quantitative Magnetic Resonance Imaging (RMI): Density at 12 Months	0.52 ratio Standard Error 0.06	0.46 ratio Standard Error 0.05

SECONDARY outcome

Timeframe: At 3 months after the intervention

Pain evaluation using a visual analogue scale (VAS) at baseline. Outcomes are expressed using a 0%-100% scale. A higher score indicates greater pain intensity

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Visual Analogue Scale at 3 Months	43 units on a scale Standard Error 9	46 units on a scale Standard Error 8

SECONDARY outcome

Timeframe: At 6 months after the intervention

Pain evaluation using a visual analogue scale (VAS) at baseline. Outcomes are expressed using a 0%-100% scale. A higher score indicates greater pain intensity

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Visual Analogue Scale at 6 Months	40 units on a scale Standard Error 8	51 units on a scale Standard Error 8

SECONDARY outcome

Timeframe: At 12 months after the intervention

Pain evaluation using a visual analogue scale (VAS) at baseline. Outcomes are expressed using a 0%-100% scale. A higher score indicates greater pain intensity

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Visual Analogue Scale at 12 Months	47 units on a scale Standard Error 10	47 units on a scale Standard Error 8

SECONDARY outcome

Timeframe: At 3 months after the intervention

Subject's Disability score in the Oswestry Disability Index (ODI) before intervention. Outcomes are expressed using a 0%-100% scale. Zero is equated with no disability and 100 is the maximum disability possible

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Oswestry Disability Index at 3 Months	16 percent Standard Error 6	25 percent Standard Error 4

SECONDARY outcome

Timeframe: At 6 months after the intervention

Subject's Disability score in the Oswestry Disability Index (ODI) before intervention. Outcomes are expressed using a 0%-100% scale. Zero is equated with no disability and 100 is the maximum disability possible

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Oswestry Disability Index at 6 Months	20 percent Standard Error 7	30 percent Standard Error 6

SECONDARY outcome

Timeframe: At 12 months after the intervention

Subject's Disability score in the Oswestry Disability Index (ODI) before intervention. Outcomes are expressed using a 0%-100% scale. Zero is equated with no disability and 100 is the maximum disability possible

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Oswestry Disability Index at 12 Months	22 percent Standard Error 7	34 percent Standard Error 7

SECONDARY outcome

Timeframe: 3 months after the intervention

Results from the physical component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
SF-12 Physical Component at 3 Months	47 units on a scale Standard Error 3	43 units on a scale Standard Error 3

SECONDARY outcome

Timeframe: 6 months after the intervention

Results from the physical component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
SF-12 Physical Component at 6 Months	46 units on a scale Standard Error 3	39 units on a scale Standard Error 3

SECONDARY outcome

Timeframe: 12 months after the intervention

Results from the physical component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
SF-12 Physical Component at 12 Months	45 units on a scale Standard Error 3	42 units on a scale Standard Error 3

SECONDARY outcome

Timeframe: 3 months after the intervention

Results from the mental component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
SF-12 Mental Component at 3 Months	50 units on a scale Standard Error 2	46 units on a scale Standard Error 3

SECONDARY outcome

Timeframe: 6 months after the intervention

Results from the mental component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
SF-12 Mental Component at 6 Months	52 units on a scale Standard Error 2	48 units on a scale Standard Error 3

SECONDARY outcome

Timeframe: 12 months after the intervention

Results from the mental component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
SF-12 Mental Component at 12 Months	48 units on a scale Standard Error 3	50 units on a scale Standard Error 3

SECONDARY outcome

Timeframe: At 6 months after the intervention

Grades:

Gr I: Disc homogeneous. Bight hyperintense white signal intensity. Normal height Gr II: Disc inhomogeneous. Hyperintense white signal. Nucleus/annulus clearly differentiated. Height is normal Gr III: Disc inhomogeneous. Intermittent gray signal intensity. Unclear distinction nucleus/annulus. Height normal/slightly decreased Gr IV: Disc inhomogeneous. Hypointense dark gray signal intensity. No distinction nucleus/annulus. Height slightly/moderately decreased.

Gr V: Disc inhomogeneous. Hypointense black signal intensity. No distinction nucleus/annulus. Disc space is collapsed

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=12 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Pfirrmann Stage at 6 Months Gr III	10 Participants	8 Participants
Pfirrmann Stage at 6 Months Gr IV	2 Participants	3 Participants
Pfirrmann Stage at 6 Months Gr II	0 Participants	1 Participants

SECONDARY outcome

Timeframe: At 12 months after the intervention

Population: One patient not evaluated

Grades:

Gr I: Disc homogeneous. Bight hyperintense white signal intensity. Normal height Gr II: Disc inhomogeneous. Hyperintense white signal. Nucleus/annulus clearly differentiated. Height is normal Gr III: Disc inhomogeneous. Intermittent gray signal intensity. Unclear distinction nucleus/annulus. Height normal/slightly decreased Gr IV: Disc inhomogeneous. Hypointense dark gray signal intensity. No distinction nucleus/annulus. Height slightly/moderately decreased.

Gr V: Disc inhomogeneous. Hypointense black signal intensity. No distinction nucleus/annulus. Disc space is collapsed

Outcome measures

Measure	Allogenic Mesenchymal Stromal Cells n=11 Participants Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 Participants Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Pfirrmann Stage at 12 Months Gr II	1 Participants	1 Participants
Pfirrmann Stage at 12 Months Gr III	9 Participants	4 Participants
Pfirrmann Stage at 12 Months Gr IV	1 Participants	7 Participants

Adverse Events

Allogenic Mesenchymal Stromal Cells

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Mepivacaine

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Allogenic Mesenchymal Stromal Cells n=12 participants at risk Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 participants at risk Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
General disorders Device failure	8.3% 1/12 • Number of events 1 • Adverse events reporting started when after the administration of the study treatments, and lasted up to the last visit of each patient at the end of the follow-up period, 12 months after the intervention.	0.00% 0/12 • Adverse events reporting started when after the administration of the study treatments, and lasted up to the last visit of each patient at the end of the follow-up period, 12 months after the intervention.

Other adverse events

Measure	Allogenic Mesenchymal Stromal Cells n=12 participants at risk Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline	Mepivacaine n=12 participants at risk Infiltration of paravertebral musculature close to the affected disc(s). The control group received a sham infiltration of paravertebral musculature with the anesthetic: saline containing 1% mepivacaine (1 ml of 2% mepivacaine + 1 ml of saline).
Musculoskeletal and connective tissue disorders Back pain	41.7% 5/12 • Number of events 8 • Adverse events reporting started when after the administration of the study treatments, and lasted up to the last visit of each patient at the end of the follow-up period, 12 months after the intervention.	75.0% 9/12 • Number of events 13 • Adverse events reporting started when after the administration of the study treatments, and lasted up to the last visit of each patient at the end of the follow-up period, 12 months after the intervention.

Additional Information

Dr. Javier García-Sancho,

CITOSPIN

Phone: 0034 983184827

Email: jgsancho@uva.es

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place