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: - Workers ( it means subject has worked at least 2 months, even if not continuously, in the last 6 months) - Age between 18 and 65 years. - Signed informed consent. - Symptomatic chronic LBP due to moderate-severe IDD [modified Pfirrmann score 3-5 (Pfirrmann et al., 2001), Griffith score 4-8 (Griffith et al., 2007)] at max. 4 levels of the lumbar spine unresponsive to conservative treatment, physical and medical for at least 6 months. Physical treatment includes physiotherapy. Medical treatments include NSAIDs, paracetamol, opioids and myorelaxant. - Annulus fibrosus intact, demonstrated by MRI. - Pain baseline > 40 mm on VAS (0- 100). - NSAIDs washout of at least 2 days before screening. - Painkillers washout of at least 24 hours before screening. - For females of childbearing potential (see definitions in paragraph 6.5), 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. The complete list of contraceptive methods is described in the patient information sheet and in paragraph 6.5. As a precautionary measure, breast-feeding should be discontinued during treatment with BM-MSC and should not be restarted after discontinuation of BM-MSC. 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 26 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: - Non-workers (it means that the person has worked less than 2 months, although not continuously, in the last 6 months) - Congenital or acquired diseases leading to spine deformations that may upset cell application (scoliosis, isthmus lesion, sacralization and hemisacralization, degenetative spondilolisthesis, previous fractures of the lumbar spine). - Spinal segmental instability assessed by dynamic X-Ray. - Symptomatic facet joints syndrome on MRI (facet joints iperintensity and ipertrophy 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. - 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 IIII 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 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/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. The complete list of contraceptive methods is described in the patient information sheet and in paragraph 6.5. - 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy of intradiscal injection of autologous BM-MSCs in workers affected by chronic LBP, due to multilevel (max. 4 levels) lumbar IDD after 12 months of treatment in terms of pain relief (VAS), functionality (ODI), quality of life (SF36) and work ability index (WAI).;Secondary Objective: 1) Evaluate regenerative changes of the treated IVD assessed by MRI including assessment of chemical biomarkers for tissue degeneration through MRI spectroscopy 2) Assess modification of employment and work status between baseline and months 12 and 24 3) Assess safety and tolerability. 4) Evaluate consumption of medications to relieve pain such as type and dose of analgesics.;Primary end point(s): To evaluate the efficacy of intradiscal injection of autologous BM-MSCs in workers affected by chronic LBP, due to multilevel (max. 4 levels) lumbar IDD, in terms of in terms of pain relief (VAS), functionality (ODI), defining responders in case of at least 40% improvement in VAS or ODI at month 12 compared to baseline and in term of quality of life (SF36) and 10% improvement on work ability index (WAI) score at month 12 compared to baseline and sham control.;Timepoint(s) of evaluation of this end point: After 12 months from the 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, T1 mapping and weighted images that allow a quantitative measure of the NP extracellular matrix and MRI spectroscopy that allow assessment of chemical biomarkers for tissue degeneration between baseline and 3, 6 and 12 months. - To evaluate modification of pain relief (VAS), disability (ODI), quality of life (SF-36) and work ability index (WAI) considered as continuos measures, between baseline and 1, 3, and 6 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