CELLKINE: Phase II Study Evaluating Safety and Preliminary Efficacy of Allogeneic, Culture-Expanded Bone Marrow-Derived Mesenchymal Stem Cells in Subjects With Painful Lumbar Facet Joint Arthropathies
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Mayo Clinic
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Narcotic Use Questionnaire
研究概览
简要总结
The purpose of this research study is to evaluate the safety and effect of bone marrow-derived stem cells for the treatment of low back pain.
详细描述
This study is a prospective, double blinded, randomized, cross over phase II study evaluating efficacy and safety of intra-articularly injected BM-MSCs in the treatment of painful facet joint arthropathy (FJA). Patients with mild to severe facet arthropathy will be considered for this study.
A total of 40 patients with diagnosis evidence of chronic low back pain associated with FJA and positive outcome of a MBB will be recruited. After confirming eligibility, patients will be randomized to Arm A: Treatment or Arm B: DMSO. After 6 months, patients randomized to Arm B: DMSO will be unblinded and may cross-over to Arm A: treatment then be followed for 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
This is a double-blind study. Patients and providers will be blinded. After 6 months, patients randomized to Arm B: DMSO will be unblinded and may crossed over to Arm A: treatment then be followed for 12 months. The statistician will generate the randomization list. Research personnel involved in patient recruitment and other activities will have no access to the randomization list.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible for inclusion into this study, the subjects must fulfill all the following criteria:
- •Male or female subjects ages 18 and older Persons of childbearing potential must be non-nursing and have a negative serum pregnancy test to be included in the trial and will agree to use adequate contraception (hormonal or barrier method or abstinence) from the time of screening to a period of up to 12 months following completion of the drug treatment cycle. Persons of childbearing potential are defined as premenopausal and not surgically sterilized, or post-menopausal for fewer than 2 years. A urine pregnancy test will be performed prior to the administration of the study drug to confirm negative results. If the urine pregnancy test is positive, the study drug will not be administered, and the result will be confirmed by a serum pregnancy test. Serum pregnancy tests will be performed at a central clinical laboratory, whereas urine pregnancy tests will be performed by qualified personnel using a kit.
- •Persons becoming pregnant during the study will continue to be monitored for the duration of the study or completion of the pregnancy, whichever is longer. Monitoring will include perinatal and neonatal outcomes. Any SAEs associated with pregnancy will be recorded. The requirement for radiation (X-ray) will be removed.
- •Clinical diagnosis of symptomatic facet joint arthropathy involving the L1-S1 facets.
- •Radiographic evidence of facet arthropathy involving the L1-S1 facets.
- •Chronic low back pain with or without referred pain to the buttock, groin, or proximal thigh.
- •Chronic low back pain is defined as the following:
- •Low back pain for at least 6 months
- •Subjects should be treated with currently available standard therapies prior to receiving an investigational product, and only subjects who do not have an adequate response to standard therapies. Have at a minimum undergone supervised physical therapy, such as daily walking routines, therapeutic exercises, and back education programs specifically for the treatment of low back pain AND taken a pain medication for back pain (e.g. NSAID and/or opioid medication).
- •Low back pain of at least 3 to 9 on numeric rating scale (NRS) (average pain in the past 7 days).
- •Confirmation of facet joint related pain by double medial branch blocks with positive results. Positive results are defined as at 75% or more improvement on pain.
- •Full understanding of the requirements of the study and willingness to comply with the treatment plan, including laboratory tests, diagnostic imaging, and follow-up visits and assessments.
- •Can provide written informed consent and complete HIPAA documentation after the nature of the study is fully explained and prior to any study-related procedure.
排除标准
- •Subjects will be excluded from participating in the study if they meet any of the following exclusion criteria:
- •Extreme obesity, as defined by NIH Clinical Guidelines Body Mass Index (BMI > 40)
- •Subjects who are pregnant or nursing or subjects planning to become pregnant during the study. If a subject becomes pregnant during the study, the subject will remain in the study and only the requirement for radiation (x-ray) will be removed.
- •Subjects with current or prior history of spinal infection at the symptomatic level (e.g. discitis, septic arthritis, epidural abscess) or an active systemic infection.
- •Subjects with a diagnosis of severe osteoporosis with pathological fracture.
- •Radiofrequency ablation at the index level prior to injection in the past 1 months with positive results. Positive results are defined as at least 50 % pain improvement on NRS back pain scale.
- •Any subject who has had previous intra-articular injection with any medication, at the planned site of MSC treatment, within the last 3 months.
- •Subjects that have undergone a procedure affecting the stability of the index facet joint. The investigator will determine whether the procedure has affected the structure/biomechanics of the index facet joint.
- •Have undergone any procedure within 12 months of the study enrollment using biological treatment for any condition such as bone marrow aspirate concentrate, PRP, bone marrow-derived MSCs, adipose-derived MSCs, SVF, micro fragmented fat, embryonic membrane product etc.
- •Clinically relevant instability on flexion-extension as determined by the primary investigator by overlaying films.
- •Have an acute fracture of the spine at the time of enrollment in the study or clinically compromised vertebral bodies at the affected level due to current or past trauma, e.g., sustained pathological fracture or multiple fractures of vertebrae.
- •Presence of any of the following spinal deformities: Pars Fractures at any facet level, spondylolisthesis > grade II at the index facet.
- •Epidural steroid injections within 4 weeks prior to treatment injection.
- •Active malignancy or tumor as a source of symptoms or history of malignancy prior to enrollment in the study, except history of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or squamous cell carcinoma of the cervix if fully excised and with clear margins.
- •An average baseline morphine equivalent dose (MED) of >50mg/day, as determined by the investigator during Screening consultation.
- •Taking systemic immunosuppressant medications or having a chronic, immunosuppressive state.
- •Taking anti-rheumatic disease medication (including methotrexate or other antimetabolites) within 3 months prior to study enrollment.
- •Clinically significant abnormal hematology (complete blood count with differential), blood chemistry, or urinalysis screening laboratory results, including PT/INR (> 1.5), PTT (< 25 or > 37 sec), AST(< 8 or > 48 U/L), ALT(< 7 or > 55 U/L) , alkaline phosphatase (ALP)(< 40 or > 129 U/L), bilirubin(>1.2mg/dL), eGFR (> 60ml/min/1.73m2), CRP(> 8.0 mg/L), and ESR(>22 mm/1h). Clinical significance is to be determined upon investigator's discretion.
- •Ongoing infectious disease, including but not limited to tuberculosis, HIV, hepatitis, and syphilis.
- •Unexplained fever, defined as greater than 100.4 degrees Fahrenheit or 38.0 degrees Celsius, or mental confusion at baseline.
- •Clinically significant cardiovascular (e.g. history of myocardial infarction, congestive heart failure or uncontrolled hypertension ≥ 140mmHg systolic and/or ≥ 90 mmHg diastolic), neurological (e.g. stroke, TIA) renal (eGFR to be > 60ml/min/1.73m2 and Stage 2, 3 and 4 of chronic kidney disease), hepatic or endocrine disease (e.g. diabetes). Clinical significance is to be determined upon investigator's discretion.
- •Participation in a study of an experimental drug or medical device for treatment of facet joint arthropathy within one year.
- •Any contraindication to MRI according to MRI guidelines or unwillingness to undergo fluoroscopic procedures
- •History of or current evidence of alcohol or drug abuse or dependence, recreational use of illicit drug or prescription medications, or have use of medical marijuana within 30 days of study entry, as determined by the investigator during Screening consultation.
- •Any illness or condition which, in the investigators' judgment will interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of the study results.
- •Being involved in active litigation related to subject's low back pain.
- •Have a mental illness that could prevent completion of the study or protocol questionnaires.
- •Subjects with a history of bleeding disorders (such as hemophilia).
- •A medical condition, serious intercurrent illness, or extenuating circumstance that would preclude participation in this study or potentially decrease survival r interfere with ambulation or rehabilitation. Examples of conditions that should be excluded are as follows:
- •history of transient ischemic attack [TIA]
- •history of stroke
- •uncontrolled diabetes
- •autoimmune disease (only if it interferes with ambulation or rehabilitation)
- •muscular dystrophy
- •rheumatoid arthritis
- •active liver disease
- •myelopathy
- •disorder of bone metabolism (osteomalacia or Paget's disease)
研究组 & 干预措施
Arm A Treatment
Participants in Arm A will be scheduled for a single set of intra-articular injections of allogeneic, culture-expanded BM-MSCs at the dose 10 x106 in 1 ml per facet joint, for a total of 2 joints to be injected. BM-MSC injections will be performed using fluoroscopic guidance.
干预措施: BM-MSC injection (Drug)
Arm B: DMSO Crossover
Participants in Arm B will receive a DMSO injection. After 6 months, participants randomized to Arm B: DMSO will be unblinded and may cross-over to Arm A: BM-MSC treatment then be followed for 12 months or continue with Arm B for another 6-month follow-up without BM-MSC injections. Each subject will be followed for study endpoints using a predetermined protocol. A final visit for evaluation and imaging will be conducted at the end of the study.
干预措施: DSMO Injection (Drug)
结局指标
主要结局
Narcotic Use Questionnaire
时间窗: 24 months
Self-reported questionnaire to assess narcotic intake. Four questions to record narcotic drug usage (yes or no), frequency and length.
Work Status Questionnaire
时间窗: 24 months
Self-reported short questionnaire to assess work status at present. Simple 3 questions to record ability to work and to attend to work.
Study personnel assessment of nature, incidence, and severity of AEs
时间窗: 24 months
Subject interview by study personnel
Clinical assessment of nature, incidence, and severity of adverse events (AEs)
时间窗: 24 months
Clinical examination face-to-face during follow-up visits
Self-reported assessment of nature, incidence, and severity of AEs
时间窗: 24 months
Spontaneous subject reports
PROMIS-CAT
时间窗: 24 months
Patient-Reported Outcomes Measurement Information System to evaluate and monitor physical, mental, and social health. Standardized response scores ranges vary from1 to 5 (e.g., 1= None to 5=Very severe) or reversed (5=None to 1=Very severe) to ensure that higher scores for responses always indicate better health.
Clinical assessment of nature, incidence, and severity of adverse events (AEs)
时间窗: Up to 18 months
Clinical examination face-to-face during follow-up visits
Self-reported assessment of nature, incidence, and severity of AEs
时间窗: Up to 18 months
Spontaneous subject reports
Study personnel assessment of nature, incidence, and severity of AEs
时间窗: Up to 18 months
Subject interview by study personnel
PROMIS-CATs
时间窗: Up to 18 months
Patient-Reported Outcomes Measurement Information System to evaluate and monitor physical, mental, and social health. Standardized response scores ranges vary from1 to 5 (e.g., 1= None to 5=Very severe) or reversed (5=None to 1=Very severe) to ensure that higher scores for responses always indicate better health.
Numeric Rating Scale (NRS) for low back pain
时间窗: Up to 18 months
A visual scale of 0 being "no pain" and 100 being "worst pain Imaginable'" to assess pain status
次要结局
- Changes from baseline evaluated by MRI(24 months)
- Changes from baseline evaluated by MRI(Up to 18 months)
- Narcotic Use Questionnaire(Up to 18 months)
- Work Status Questionnaire(Up to 18 months)