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

NCT ID: NCT03737461

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 113 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-18
• Study Completion Date: 2026-03-08

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.

Conditions

Recurrent Low Back Pain; Degenerative Disc Disease (DDD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Allogenic BM-MSCs Injection

Intervention Type: DRUG

Cell dose will be 20±5 million cells suspended in 2 ml of HypoThermosol isotonic transport solution

Sham Procedure

anesthetic infiltration with 2 ml of 1% xylocaine in the paravertebral muscles close to the affected segment

Group Type: SHAM_COMPARATOR

Sham Procedure

Intervention Type: OTHER

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.

Interventions

Allogenic BM-MSCs Injection

Cell dose will be 20±5 million cells suspended in 2 ml of HypoThermosol isotonic transport solution

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

Injection of 2 mL of 1% xylocaine

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Interdisziplinäres Zentrum Klinische Studien (IZKS)

UNKNOWN

Sponsor Role: collaborator

European Clinical Research Infrastructure Network

OTHER

Sponsor Role: collaborator

Département de l'information médicale, CHU de Montpellier

UNKNOWN

Sponsor Role: collaborator

Centre National de la Recherche Scientifique, France

OTHER

Sponsor Role: collaborator

Université Montpellier

OTHER

Sponsor Role: collaborator

Univercell-Biosolutions S.A.S

UNKNOWN

Sponsor Role: collaborator

National University of Ireland, Galway, Ireland

OTHER

Sponsor Role: collaborator

University of Valladolid

OTHER

Sponsor Role: collaborator

Citospin

INDUSTRY

Sponsor Role: collaborator

Rennes University Hospital

OTHER

Sponsor Role: collaborator

APHP

OTHER

Sponsor Role: collaborator

Campus Bio-Medico University

OTHER

Sponsor Role: collaborator

BG Klinikum Bergmannstrost, Halle, Germany

UNKNOWN

Sponsor Role: collaborator

Nantes University Hospital

OTHER

Sponsor Role: collaborator

Institut de Terapia Regenerativa Tissular

OTHER

Sponsor Role: collaborator

University of Navarra

OTHER

Sponsor Role: collaborator

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian CJ JORGENSEN, PhD

Role: PRINCIPAL_INVESTIGATOR

Montpellier University Hospital

Locations

UH Montpellier

Montpellier, , France

CHU de Nantes

Nantes, , France

CHU Saint Antoine

Paris, , France

APHP Cochin

Paris, , France

BG Klinikum Bergmannstrost

Halle, , Germany

Campus Bio-Medico University of Rome

Roma, , Italy

Institut de Teràpia Regenerativa Tissular

Barcelona, , Spain

Clínica Universidad de Navarra

Pamplona, , Spain

Hospital Sagrado Corazón Valladolid

Valladolid, , Spain

Countries

France; Germany; Italy; Spain

References

Pers YM, Soler-Rich R, Vadala G, Ferreira R, Duflos C, Picot MC, Herman F, Broussous S, Sanchez A, Noriega D, Ardura F, Alberca Zaballos M, Garcia V, Gordillo Cano V, Gonzalez-Vallinas M, Denaro V, Russo F, Guicheux J, Vilanova J, Orozco L, Meisel HJ, Alfonso M, Rannou F, Maugars Y, Berenbaum F, Barry FP, Tarte K, Louis-Plence P, Ferreira-Dos-Santos G, Garcia-Sancho J, Jorgensen C; RESPINE consortium. Allogenic bone marrow-derived mesenchymal stromal cell-based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study). Ann Rheum Dis. 2024 Oct 21;83(11):1572-1583. doi: 10.1136/ard-2024-225771.

Reference Type: DERIVED

PMID: 39393844 (View on PubMed)

Other Identifiers

2017-002092-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RECHMPL17_0206

Identifier Type: -

Identifier Source: org_study_id