Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03737461
Previous Study | Return to List | Next Study

Efficacy of Intradiscal Injection of BM-MSC in Subjects With Chronic Low Back Pain (LBP) Due to Lumbar Degenerative Disc Disease (DDD) Unresponsive (RESPINE)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03737461
Recruitment Status : Recruiting
First Posted : November 9, 2018
Last Update Posted : April 10, 2020
Sponsor:
Collaborators:
Interdisziplinäres Zentrum Klinische Studien (IZKS)
European Clinical Research Infrastructure Network
Département de l'information médicale, CHU de Montpellier
Centre National de la Recherche Scientifique, France
Université Montpellier
Univercell-Biosolutions S.A.S
National University of Ireland, Galway, Ireland
University of Valladolid
Citospin
Rennes University Hospital
APHP
Campus Bio-Medico University
BG Klinikum Bergmannstrost, Halle, Germany
Nantes University Hospital
Institut de Terapia Regenerativa Tissular
University of Navarra
Information provided by (Responsible Party):
University Hospital, Montpellier

Tracking Information
First Submitted Date  ICMJE June 19, 2018
First Posted Date  ICMJE November 9, 2018
Last Update Posted Date April 10, 2020
Actual Study Start Date  ICMJE February 18, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 8, 2018)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2018)
  • 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
    • Analgesics
    • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Intradiscal Injection of BM-MSC in Subjects With Chronic Low Back Pain (LBP) Due to Lumbar Degenerative Disc Disease (DDD) Unresponsive
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description Degenerative disc disease (DDD) presents a large, unmet medical need. One of the most important public health problems, it affects 70 million Europeans, accounts for 42% of patients with chronic low back pain and costs over $100 billion each year in the European Union. DDD results in a disabling loss of mechanical function. Today, no efficient therapy is available. The disease results from degeneration of cartilage discs with loss of the collagen matrix and nucleus pulposus chondrocyte. Chronic cases often receive surgery, which may lead to biomechanical problems and accelerated degeneration of adjacent segments. Our consortium partners have developed and studied stem cell-based, regenerative therapies with encouraging results in phase 1 and 2 trials. Patients exhibited rapid and progressive improvement of functional and pain indexes by 50% within 6 months and by 65% to 78% after 1 year with no side effects. In addition, MRI T2 relaxation measurements demonstrated a significant improvement of cartilage signal. To develop the world's first effective treatment of DDD, RESPINE aims to assess, via a randomized, controlled, phase 3 clinical trial including 112 patients with DDD, the efficacy of an allogenic intervertebral mesenchymal stem cell (MSC)-based therapy. This innovative therapy aims to rapidly (within 3 months) and durably (at least 24 months) reduce pain and disability. In addition, the consortium aims to provide new knowledge on immune response & safety associated with allogeneic BM-MSC intradiscal injection.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Low Back Pain
  • Degenerative Disc Disease (DDD)
Intervention  ICMJE
  • Drug: Allogenic BM-MSCs Injection
    Cell dose will be 20±5 million cells suspended in 2 ml of HypoThermosol isotonic transport solution
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Allogenic BM-MSCs Injection
  • Sham Comparator: Sham Procedure
    anesthetic infiltration with 2 ml of 1% xylocaine in the paravertebral muscles close to the affected segment
    Intervention: Other: Sham Procedure
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 8, 2018)
112
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christian CJ JORGENSEN, PhD 0033 467 337798 c-jorgensen@chu-montpellier.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03737461
Other Study ID Numbers  ICMJE UF 9766
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Montpellier
Study Sponsor  ICMJE University Hospital, Montpellier
Collaborators  ICMJE
  • Interdisziplinäres Zentrum Klinische Studien (IZKS)
  • European Clinical Research Infrastructure Network
  • Département de l'information médicale, CHU de Montpellier
  • Centre National de la Recherche Scientifique, France
  • Université Montpellier
  • Univercell-Biosolutions S.A.S
  • National University of Ireland, Galway, Ireland
  • University of Valladolid
  • Citospin
  • Rennes University Hospital
  • APHP
  • Campus Bio-Medico University
  • BG Klinikum Bergmannstrost, Halle, Germany
  • Nantes University Hospital
  • Institut de Terapia Regenerativa Tissular
  • University of Navarra
Investigators  ICMJE
Principal Investigator: Christian CJ JORGENSEN, PhD Montpellier University Hospital
PRS Account University Hospital, Montpellier
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP