- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03737461
Efficacy of Intradiscal Injection of BM-MSC in Subjects With Chronic Low Back Pain (LBP) Due to Lumbar Degenerative Disc Disease (DDD) Unresponsive (RESPINE)
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
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.
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Montpellier, France, 34295
- UH Montpellier
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Nantes, France
- CHU de Nantes
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Paris, France
- Aphp Cochin
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Paris, France, 75012
- CHU Saint Antoine
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Halle, Germany, 06112
- BG Klinikum Bergmannstrost
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Roma, Italy, 00128
- Campus Bio-Medico University of Rome
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Barcelona, Spain, 08022
- Institut de Teràpia Regenerativa Tissular
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Pamplona, Spain, 31008
- Clinica Universidad de Navarra
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Valladolid, Spain, 47002
- Hospital Sagrado Corazón Valladolid
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age between 18 and 60 years.
- Symptomatic chronic low back pain unresponsive to conservative therapy (including physical therapy performed during at least 1 month before inclusion and pain medication with level 2 analgesics in failure or intolerant to level during at least 1 month) for at least 3 months.
- DDD assessed by (Pfirrmann's score modified Griffith et al) grade 4 to 7 at one level. If second level, it should be adjacent (Pfirrmann's score 1-4 maximum)
- Low back Pain baseline > 40 mm on VAS (0-100).
- NSAID washout of at least 2 days before screening
- Painkillers washout of at least 24 hours before screening
Exclusion Criteria:
- Congenital or acquired diseases leading to spine deformations that may upset cell application (hyperlordosis, scoliosis, isthmus lesion, sacralization and hemisacralization).
- Symptomatic posterior lumbo-articular osteoarthritis or predominant facet syndrome on Xray or MRI (osteophyte and facet hypertrophy).
- Prior to the screening visit, has received:
- Oral corticosteroid therapy within the previous 3 months, OR
- Intramuscular, intravenous or epidural corticosteroid therapy within the previous 3 months
- Spinal segmental instability (defined by lumbar dynamic X-Ray in extension/flexion with antero-post translation > 3 mm and/or angular mobility > 15°).
- Spinal canal stenosis (Schizas score > B).
- History of spinal infection.
- Lumbar disc herniation with non truncated sciatica or cruralgia, as well as lumbar cysts and radiculopathy
- Previous discal puncture or previous spine surgery.
- DDD on 3 levels, or DDD on 2 levels but not adjacent, or DDD with modic 2 or 3 phases
- Patients not eligible to the intravertebral disc surgery
- Patients who have the risk to undergo a surgery in the next 6 months
- Obesity with body mass index (BMI in Kg/size in m2) greater than 35 (obesity grade II).
- Participation in another clinical trial or treatment with another investigational product within 30 days prior to inclusion in the study.
- Abnormal blood tests: hepatic (alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 × upper limit of normal (ULN)), renal, pancreatic or biliary disease, blood coagulation disorders, anemia or platelet count of <100 × 109/
- Significant medical problems, such as uncontrolled hypertension, symptomatic heart failure; or any other clinically relevant condition or current medication that in the opinion of the investigator contra-indicates the use of any of the study or rescue medications.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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Cell dose will be 20±5 million cells suspended in 2 ml of HypoThermosol isotonic transport solution
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Sham Comparator: Sham Procedure
anesthetic infiltration with 2 ml of 1% xylocaine in the paravertebral muscles close to the affected segment
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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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change from Baseline Pain Clinical response at 12 months
Time Frame: baseline to month 12
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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.
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baseline to month 12
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Change from Baseline Oswestry Disability Index (ODI) measure at 12 months
Time Frame: baseline to month 12
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at least 20% improvement of functional index ODI at month 12 compared to baseline.
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baseline to month 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Measure disability and quality of life evolution of the patient
Time Frame: Baseline, 3,6,12 and 24 months
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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. |
Baseline, 3,6,12 and 24 months
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Disability and quality of life evolution
Time Frame: baseline, 3,6,12 and 24 months
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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.
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baseline, 3,6,12 and 24 months
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Pain killers
Time Frame: baseline, 1, 3,6,12 and 24 months
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assessement of consumption of painkillers medication.
Rescue medication use will be recorded throughout the study duration by a diary file.
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baseline, 1, 3,6,12 and 24 months
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Measure of the Chronic low back pain
Time Frame: baseline, 1, 3,6,12 and 24 months
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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.
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baseline, 1, 3,6,12 and 24 months
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Employment and work status
Time Frame: baseline, 1, 3,6,12 and 24 months
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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.
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baseline, 1, 3,6,12 and 24 months
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Structural assessment
Time Frame: baseline, 1, 3,6,12 and 24 months
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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).
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baseline, 1, 3,6,12 and 24 months
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Evaluation of cost
Time Frame: 24 months
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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:
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24 months
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Immune response / Analytical control
Time Frame: baseline, 1, and 6 months
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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.
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baseline, 1, and 6 months
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reporting of Serious Adverse Events (SAE)
Time Frame: baseline, 1, 3,6,12 and 24 months
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Define the safety outcomes of the clinical trial with the record of SAE
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baseline, 1, 3,6,12 and 24 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Christian CJ JORGENSEN, PhD, Montpellier University Hospital
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pain
- Neurologic Manifestations
- Musculoskeletal Diseases
- Spinal Diseases
- Bone Diseases
- Back Pain
- Low Back Pain
- Intervertebral Disc Degeneration
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Sensory System Agents
- Anesthetics
- Membrane Transport Modulators
- Anesthetics, Local
- Voltage-Gated Sodium Channel Blockers
- Sodium Channel Blockers
- Lidocaine
Other Study ID Numbers
- UF 9766
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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