Efficacy of Intradiscal Injection of BM-MSC in Subjects With Chronic Low Back Pain (LBP) Due to Lumbar Degenerative Disc Disease (DDD) Unresponsive (RESPINE)
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|ClinicalTrials.gov Identifier: NCT03737461|
Recruitment Status : Recruiting
First Posted : November 9, 2018
Last Update Posted : April 10, 2020
This will be a multicenter, prospective, double blind, randomized phase 2/3 trial comparing culture-expanded allogeneic adult BM-MSCs with sham-treated controls.
This trial will evaluate the efficacy of intradiscal injection of BM-MSCs in chronic low back pain due to lumbar degenerative disc disease (DDD) unresponsive to conventional therapy .
Visual analog scale (VAS) and functional status (by Oswestry Disability Index - ODI) will be evaluated 12 months after treatment, defining responders in case of improvement of VAS for pain of at least 20% and 20 mm between baseline and month 12, or improvement of ODI of 20% between baseline and month 12.
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Low Back Pain Degenerative Disc Disease (DDD)||Drug: Allogenic BM-MSCs Injection Other: Sham Procedure||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||112 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||A Phase 2/3 Prospective, Multicentre Randomized, Double-blind Trial, Comparing Intra-discal Allogeneic Adult BM-MSC Therapy and Sham-treated Controls in Subjects With Chronic LBP Due to Lumbar DDD Unresponsive to Conventional Therapy|
|Actual Study Start Date :||February 18, 2019|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2022|
Experimental: Allogenic BM-MSCs Injection
Injection of a dose of 20.106 allogenic BM-MSCs via imaging control into the disk affected by DDD where they are expected to exert their therapeutic effects.
Drug: Allogenic BM-MSCs Injection
Cell dose will be 20±5 million cells suspended in 2 ml of HypoThermosol isotonic transport solution
Sham Comparator: Sham Procedure
anesthetic infiltration with 2 ml of 1% xylocaine in the paravertebral muscles close to the affected segment
Other: Sham Procedure
sham-maneuver as in the cell-treated patients are added, consisting in anesthetic infiltration with 2 ml of 1% xylocaine in the paravertebral muscles close to the affected segment.
Other Name: Injection of 2 mL of 1% xylocaine
- Change from Baseline Pain Clinical response at 12 months [ Time Frame: baseline to month 12 ]The clinical response is defined as the Pain relief measure with Visual Analogue Scale (VAS) of at least 20 mm decrease on VAS scale between baseline and month 12.
- Change from Baseline Oswestry Disability Index (ODI) measure at 12 months [ Time Frame: baseline to month 12 ]at least 20% improvement of functional index ODI at month 12 compared to baseline.
- Measure disability and quality of life evolution of the patient [ Time Frame: Baseline, 3,6,12 and 24 months ]
Assessed by Short Form-36 Health Survey (SF-36) :
The eight sections are vitality, physical functioning, bodily pain, general health, perceptions, physical role functioning, emotional role functioning, social role functioning and mental health A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
- Disability and quality of life evolution [ Time Frame: baseline, 3,6,12 and 24 months ]global assessment by the patient and the physician. Overall pain intensity in the lumbar spine (1 = none, 2 = mild, 3 = moderate, 4 = severe, 5 = extreme); patient's global assessment of disease activity (1 = very good, 2 = good, 3 = fair, 4 = poor, 5 = very poor); physician's global assessment of disease activity (1 = very good, 2 = good, 3 = fair, 4 = poor, 5 = very poor) will be performed at 0, 3, 6, 12 and 24 months.
- Pain killers [ Time Frame: baseline, 1, 3,6,12 and 24 months ]assessement of consumption of painkillers medication. Rescue medication use will be recorded throughout the study duration by a diary file.
- Measure of the Chronic low back pain [ Time Frame: baseline, 1, 3,6,12 and 24 months ]assessement of pain by the Visual Analogue pain Scale (VAS) during 24 months. Min value 0 - max value 100 , where 0 represents no pain and 100 represents the worst pain imaginable.
- Employment and work status [ Time Frame: baseline, 1, 3,6,12 and 24 months ]Assessement of employment and work status. For this, patients will be assign to one of 4 categories designated as "employable" which included those who were unemployed due to pain, employed but on sick leave, laid off, or working. The other categories include retired, disabled, and elderly at least 60 years of age, eligible for social security.
- Structural assessment [ Time Frame: baseline, 1, 3,6,12 and 24 months ]Evolution of affected disc(s) by quantitative Magnetic Resonance Imaging (MRI) density measurements in T2 and T1spin/echo and T1rho weighted images performed at 0, 6 12 and 24 months used as an indication of disc fluid and glycosaminoglycan (GAG) content. The "quality" of the patient's lumbar disc will be monitored non invasively using T2-weighted MRI sagittal images (Orozco et al., 2011) and, in T1spin/echo MRI. Lumbar disc grading will be performed in the sagittal T2 weighted images by two physicians independently who were experienced in MRI of the spine. They will review each intervertebral disc from L1-2 to L5-S1 by the modified Pfirrmann criteria. The modified Pfirrmann grading system assesses degenerated intervertebral discs by MRI for the asymmetry in disc structure, distinction of the nucleus and the annulus, signal intensity of intervertebral discs and height of intervertebral discs and assigns grade 1 to 8 for disc degeneration (Table by Griffin et al. Spine 2007).
- Evaluation of cost [ Time Frame: 24 months ]
We will compare the medical and non-medical costs between the two groups of patient. Costs will be identified for a one-year time horizon.
For this purpose, resource use in each arm will be collected in physical units in the electronic Case Report Form (eCRF) at each clinical centre as follows:
- Acute care medical hospitalisations related to DDD
- Acute care surgical hospitalisations related to DDD
- Rehabilitation hospitalisations related to DDD
- Work disruption Resource use will be valued using production costs specific to each country or to the country having included the highest number of patients, depending on the number of patients actually included in each clinical centre.
- Immune response / Analytical control [ Time Frame: baseline, 1, and 6 months ]The assessment of the biological effect of allogeneic MSC on recipient immune response will be studied by multiparametric flow-cytometry as well as monitoring of anti HLA-I (human leukocyte antigen I) antibodies response.
- reporting of Serious Adverse Events (SAE) [ Time Frame: baseline, 1, 3,6,12 and 24 months ]Define the safety outcomes of the clinical trial with the record of SAE
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03737461
|Contact: Christian CJ JORGENSEN, PhD||0033 467 firstname.lastname@example.org|
|Montpellier, France, 34295|
|Contact: Christian Jorgensen, MD 0033 467 337798 email@example.com|
|Contact: Yves Marie PERS, MD firstname.lastname@example.org|
|Principal Investigator: Christian Jorgensen, MD|
|CHU Saint Antoine||Recruiting|
|Paris, France, 75012|
|Contact: Francis BERENBAUM, PU-PH 01 49 28 25 20 email@example.com|
|Principal Investigator: Francis BERENBAUM, PU-PH|
|APHP Cochin||Not yet recruiting|
|Contact: François RANNOU, PhD|
|Principal Investigator:||Christian CJ JORGENSEN, PhD||Montpellier University Hospital|