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 low back pain due to lumbar degenerative disc disease (DDD) unresponsive to conventional therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Clinical response is defined as pain relief of at least 20% and 20 mm decrease on VAS scale between baseline and month 12, or 20% improvement of functional index ODI at month 12 compared to baseline. VAS pain scale (0 – 100, where 0 represents no pain and 100 represents the worst pain imaginable). Oswestry disability index scale ranges from 0 to 50 (0%–20%:minimal disability; 20%–40%:moderate disability; 40%–60%:severe disability; 60%–80%:crippled; 80%–100%:bed-bound/exaggerating their symptoms
研究概览
简要总结
The first co-primary objective is to assess the efficacy of intradiscal injection of allogeneic BM-MSCs in reducing chronic low back pain due to lumbar DDD using the visual analog scale (VAS) and functional status assessed by the Oswestry disability index (ODI) after 12 months of treatment, defining a responder as a patient with an improvement of VAS for pain of at least 20% and 20 mm between baseline and month 12, or with an improvement of ODI of 20% between baseline and month 12. The second co-primary objective is to assess the efficacy of intradiscal injection of allogeneic BM-MSCs in increasing disc fluid content, measured by quantitative Magnetic Resonance Imaging, between baseline and month 12.
研究设计
- 分配方式
- Randomized
- 主要目的
- M24 To M60 (germany Only)
- 盲法
- Double (Subject, Investigator, Carer)
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 60 years at pre-screening visit
- •Symptomatic chronic low back pain unresponsive to conservative therapy (including 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 at screening > 40 mm on VAS (0-100)
- •NSAID washout of at least 2 days before screening
- •Painkillers washout of at least 24 hours before screening
排除标准
- •Congenital or acquired diseases leading to spine deformations that may upset cell application (hyperlordosis, scoliosis, isthmus lesion, sacralisation and hemisacralisation)
- •Patients contre-indicated to intravertebral disc rescue 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 × 10^9/L
- •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
- •Pregnant or lactating women, or premenopausal women not using an acceptable form of birth control, are ineligible for inclusion. Contraception has to be maintained during treatment and until the individual end of the study (M24). In each case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is strongly recommended. Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation : oral, injectable, implantable, intrauterine device (IUD), intrauterine hormone-releasing system ( IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence are ineligible for inclusion.
- •Positive serology for following infection: Syphilis, HIV, Hepatitis B, Hepatitis C or HTLV
- •Contraindication to MRI assessed by the investigator
- •Intolerance or allergy to local anesthesia
- •Symptomatic posterior lumbo-articular osteoarthritis or predominant facet syndrome (osteophyte and facet hypertrophy)
- •Any history of Cancer or immunodeficiency disease
- •History of transfusion or transplantation
- •Current sick leave due to work accident
- •Prisoners or subjects who are involuntary incarcerated
- •Patients subject to legal protection measures
- •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
- •History of 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 2 or 3 levels but not adjacent, or DDD with modic 2 or 3 phases
结局指标
主要结局
Clinical response is defined as pain relief of at least 20% and 20 mm decrease on VAS scale between baseline and month 12, or 20% improvement of functional index ODI at month 12 compared to baseline. VAS pain scale (0 – 100, where 0 represents no pain and 100 represents the worst pain imaginable). Oswestry disability index scale ranges from 0 to 50 (0%–20%:minimal disability; 20%–40%:moderate disability; 40%–60%:severe disability; 60%–80%:crippled; 80%–100%:bed-bound/exaggerating their symptoms
Clinical response is defined as pain relief of at least 20% and 20 mm decrease on VAS scale between baseline and month 12, or 20% improvement of functional index ODI at month 12 compared to baseline. VAS pain scale (0 – 100, where 0 represents no pain and 100 represents the worst pain imaginable). Oswestry disability index scale ranges from 0 to 50 (0%–20%:minimal disability; 20%–40%:moderate disability; 40%–60%:severe disability; 60%–80%:crippled; 80%–100%:bed-bound/exaggerating their symptoms
Fluid content of the discs will be determined from T2-weighted sagittal images, and measured in the affected disc segment and in the contiguous 3 to 5 segments (Methods and Orozco et al). The fluid content values of the affected discs will be normalized to the values obtained from the healthy discs in the same individual (average value of the healthy discs). The change in fluid content is expressed as the ratio of fluid content at months 12 vs fluid content at baseline.
Fluid content of the discs will be determined from T2-weighted sagittal images, and measured in the affected disc segment and in the contiguous 3 to 5 segments (Methods and Orozco et al). The fluid content values of the affected discs will be normalized to the values obtained from the healthy discs in the same individual (average value of the healthy discs). The change in fluid content is expressed as the ratio of fluid content at months 12 vs fluid content at baseline.
Evolution of affected disc(s) by quantitative Magnetic Resonance Imaging (MRI) density measurements in T2 and T1spin/echo and T1rho weighted images performed at screening, 12 and 24 months used as an indication of disc fluid and GAG content. The "quality" of the patient's lumbar disc will be monitored non-invasively using T2-weighted MRI sagittal images and, in T1spin/echo MRI.
Evolution of affected disc(s) by quantitative Magnetic Resonance Imaging (MRI) density measurements in T2 and T1spin/echo and T1rho weighted images performed at screening, 12 and 24 months used as an indication of disc fluid and GAG content. The "quality" of the patient's lumbar disc will be monitored non-invasively using T2-weighted MRI sagittal images and, in T1spin/echo MRI.
次要结局
- Disability and quality of life evolution include Short Form (SF)-36 scores, 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)
- de-/increase in rescue painkillers medication
- drug consumption of painkillers
- Employment and work status
- medical and non-medical costs
- Immune response
- Safety Outcomes
研究者
Christian JORGENSEN
Scientific
University Hospital Of Montpellier