Efficacy of Intradiscal Injection of Autologous BM-MSC in Subjects With Chronic LBP Due to Multilevel Lumbar IDD

• Status: Recruiting
• Trial end date: 2023-06-09
• Target enrollment: 0
• Participant gender: All

Summary

DREAM is a phase II B efficacy monocentric, prospective, randomized, controlled double blinded trial, comparing intra-discal autologous adult bone marrow mesenchymal stem cells (BM-MSC) therapy and sham treated controls in subjects with chronic (> 6 months) Low Back Pain (LBP) due to lumbar multilevel (max. 3 levels) intervertebral disc degeneration (IDD) unresponsive to conventional therapy.

Duration of the recruitment period has been estimated to be 12 months. The efficacy of intradiscal injection of autologous BM-MSC in reducing chronic LBP due to multilevel lumbar IDD will be evaluated after 24 months in terms of pain relief (VAS), functionality (ODI) and quality of life (SF36).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Campus Bio-Medico University
• Collaborators: Center for Outcomes Research and Clinical Epidemiology, Italy; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Criteria

Inclusion Criteria:

• Signed informed consent.

• Symptomatic chronic LBP due to moderate IDD (modified Pfirrmann score 3-4, Griffith score 3-7) at max.3 levels of the lumbar spine unresponsive to conservative treatment, physical and medical for at least 6 months. Physical treatment includes physiotherapy. Medical treatments includes nonsteroidal anti-inflammatory drugs (NSAID), paracetamol, opioids and myorelaxant.

• Annulus fibrosus intact, demonstrated by MRI.

• 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.

• For females of childbearing potential, a negative pregnancy test must be documented at Screening.

• Men and women should use effective contraception during treatment and for at least 24 months after BM-MSC discontinuation. As a precautionary measure, breast-feeding should be discontinued during treatment with BM-MSC and should not be restarted after discontinuation of BM-MSC.

Exclusion Criteria:

• Congenital or acquired diseases leading to spine deformations that may upset cell application (scoliosis, isthmus lesion, sacralization and hemisacralization, degenerative spondylolisthesis).

• Spinal segmental instability assessed by dynamic X-Ray.

• Symptomatic facet joints syndrome on MRI (facet joints hyperintensity and hypertrophy evaluated at coronal T2 weighted MRI).

• 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

• Presence of a 4th level with symptomatic IDD (modified Pfirrmann score 3-4, Griffith score 3-7) in the lumbar spine.

• Spinal canal stenosis (Schizas score > B).

• History of spinal infection.

• Lumbar disc herniation and sciatica.

• Endplate abnormality such as Schmorl's Nodes.

• Previous discal puncture or previous spine surgery.

• IDD with Modic II and III changes on MRI images.

• Patients not eligible to the intravertebral disc surgery.

• Patients who have the risk to undergo a surgery in the next 6 months.

• Patients with local infusion device/devices for corticosteroids.

• Obesity with body mass index (BMI in Kg/size in m^2) 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 amino transferase [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 × 10^9/L.

• Pregnant or lactating women, or premenopausal women not using an acceptable form of birth control, are ineligible for inclusion. Contraception will be maintained during treatment and until the end of relevant systemic exposure. Additional pregnancy testing will be performed at the end of relevant systemic exposure. The patients will be required to use contraception from initial treatment administration until 24 months after the last dose of study drug.

• In each case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is strongly recommended.

• Positive serology for following infection: Syphilis, HIV, Hepatitis B, or C.

• Contraindication to MRI assessed by the investigator.

• Intolerance or allergy to local anaesthesia.

• Any history of Cancer or immunodeficiency disease.

• Previous transplantation.