Symptomatic chronic low back pain due to a degenerative disease of the intervertebral disc MedDRA version: 21.0 Level: LLT Classification code 10070241 Term: Degenerative disc disease System Organ Class: 100000004859
Conditions
Sponsors
UNIVERSITÀ CAMPUS BIO-MEDICO DI ROMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Subjects aged between 18 and 65 years. • Signed informed consent. • Chronic symptomatic LBP due to moderate IDD (Grade 3-4 according to Pfirrmann, grade 3-7 according to Griffith) at up to 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 AINS, paracetamol, opioids and myorelaxant. (For more details, see paragragh 1.1.4) • Annulus fibrosus intact, confirmed by magnetic resonance imaging (MRI). • Pain in the lumbar area at the baseline> 40 mm on the VAS scale (0-100). • Washout of NSAIDs at least 2 days before the screening visit. • Wshout of painkillers at least 24 hours before the screening visit. • Women of child-bearing age, they must take a pregnancy test at the time of the screening visit which must be negative. • Men and women should use effective contraception during treatment and for at least 24 months after stopping BM-MSC therapy. As a precautionary measure, breastfeeding should be discontinued during the study treatment period and should not be resumed after BM-MSC injections are stopped Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 52 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
Exclusion criteria: Congenital or acquired diseases that lead to a deformation of the vertebral column and can compromise the injection of cells (scoliosis, isthmus lesions, sacralization and hemisacralization, degenerative spondylolisthesis). • Instability of the spinal segment assessed by dimanic radiography of the column (RX) • Joint facet syndrome evaluated with MRI (hyperintensity and hypertrophy of the facet joints in T2-weighted images). • Patients who have taken before the screening visit: - Oral corticosteroid therapy in the three months prior to treatment, - Intramuscular, intravenous or epidural infusion of corticosteroids in the three months prior to treatment • Presence of a 4th level with symptomatic IDD, (Grade 3-4 according to Pfirrmann, grade 3-7 according to Griffith) at the vertebral column level. • Stenosis of the spinal canal (Schizas score> B). • Clinical history of spinal infections. • Disc herniation and sciatica. • Anomaly of the terminal disks, such as Schmorl's hernias. • Previous injections at the level of the disc or previous surgery on the spinal column. • IDD with Modic II and III modifications evaluated with images obtained from MRI. • Patients not suitable for intervertebral disc surgery. • Patients who have the risk of having surgery in the 6 months following inclusion in the study. • Patients with local infusion device/devices for corticosteroids. • Obese patients with a body mass index (BMI expressed as weight Kg / m2) greater than 35 (degree of obesity II). • Subjects participating in another clinical trial or being treated with another experimental medicine within 30 days prior to inclusion in the study. • Abnormal blood tests: hepatic values ¿¿(alanine transferase [ALT] and / or aspartate aminotransferase [AST]> 1.5 beyond the limits of the standard [ULN], • renal, pancreatic or biliary disorders, coagulation disorders, anemia and platelet counts <100 x 109 / L. • Women who are pregnant or nursing, or pre-menopausal women who do not use an acceptable precautionary contraceptive method, are not eligible for the study. Contraception should be maintained throughout the treatment period until the end of the study. An additional pregnancy test will be performed at the end of the study. Patients are required to use contraceptive methods from the start of treatment and up to 24 months after the last dose of the experimental medicine. • In any case of delay of the menstrual period (over an interval of one month between the two periods), it is strongly recommended to exclude the possibility of a possible pregnancy. The complete list of contraceptive methods is described in the patient information sheet and in section 6.5. • Serological positivity for the following infections: Syphilis, HIV, Hepatitis B or C • Not suitable for MRI evaluated by the investigator. • Intolerance or allergy to local anesthesia. • Any clinical history of cancer or immunodeficiency disease. • Previous transplant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective is to evaluate the efficacy of intradiscal injection of autologous BM-MSC cells in reducing chronic low back pain (LBP) due to a multilevel lumbar intervertebral disc (IDD) degeneration (max. 3 levels) 24 months after treatment in terms of pain reduction (VAS), improved function (ODI) and quality of life (SF36).;Secondary Objective: • Evaluate the regenerative changes of the treated discs. • Evaluate the change in employment and work status between the baseline and the 12 and 24 months. • Assess the safety and tolerability of the treatment. • Evaluate the use of drugs used to relieve pain, indicating the type and dose of analgesic.;Primary end point(s): To evaluate the efficacy of intradiscal injection of autologous BM-MSC using the visual analog scale (VAS) and functional status assessed by the Oswestry disability index (ODI) after 24 months of treatment, defining responders in case of at least 40% improvement in VAS or ODI at month 24 compared to baseline.;Timepoint(s) of evaluation of this end point: After 24 months from treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To evaluate changes of the treated IVD induced by regenerative therapy by quantitative Magnetic Resonance Imaging (MRI) signal measurements in T2, T1spin/echo, and T1rho weighted images that allow a quantitative measure of the NP extracellular matrix. - To evaluate modification of disability (ODI) and quality of life (SF-36 scores) considered as continuos measures, between baseline and 1, 3, 6, 12 and 24 months. - Safety and tolerability will be evaluated by recording adverse events (AEs) and serious AEs (SAEs) throughout the study till 24 months. Number of participants with adverse events, the correlation of the AE to the IMP and their severity will be used as a measure of safety and tolerability. - To evaluate consumption of medications to relieve pain such as type and dose of analgesics will be evaluated. Paracetamol (acetaminophen) and levels 2 analgesics will be assessed throughout the study at each visit.;Timepoint(s) of evaluation of this end point: Between baseline and 1,3,6,12 and 24 months. | — |
Countries
Italy
Contacts
Public ContactCentro Dati GIMEMA
Fondazione GIMEMA
Outcome results
None listed