Clinical trial NCT04410731: Allogeneic BM-MSCs in Patients with Lumbar Facet Arthropathy
Official title: CellKine: Phase I Study Evaluating the Safety and Feasibility of Allogeneic, Culture-Expanded Bone Marrow-Derived Mesenchymal Stem Cells in Subjects with Painful Lumbar Facet Joint Arthropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Facet-Mediated Low Back Pain
Keywords: lumbar pain
facet joint
arthropathy
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2020-06-01
Enrollment: 10
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Staggered enrollment for subjects 1 to 3, followed by conditioned open enrollment for subjects 4 to 10.
Primary purpose: TREATMENT

Brief summary: Researchers are conducting this study to learn more about the side effects of bone marrow-derived stem cells when injected into the facet joints for the treatment of painful lumbar facet joint arthropathies.

Detailed description: Phase I prospective study to determine the safety and feasibility of allogeneic, culture-expanded BM-MSCs in subjects with painful facet-mediated low back pain. Target accrual is 10 subjects with diagnosis of painful lumbar facet joint arthropathy. Eligible subjects will receive a single set of intra-articular bilateral injections of allogeneic, culture-expanded BM-MSCs human, allogeneic, culture expanded, bone-marrow-derived mesenchymal stem cells. Subjects will be evaluated at baseline, treatment day 0, post-operative day 1, post-operative days 3-5, week 2, and months 3, 6, 12, 18 and 24 months post-treatment.

Eligibility criteria: Inclusion Criteria:

Male or female subjects ages 40-70 years who fulfill the following criteria:

1. 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 24 months following completion of the drug treatment cycle.
2. Clinical diagnosis of symptomatic facet joint arthropathy involving the L3-S1 facets.
3. Radiographic evidence of facet arthropathy involving the L3-S1 facets.
4. Chronic low back pain with or without referred pain to the buttock, groin, or proximal thigh.
5. Confirmation of facet joint related pain by medial branch block with positive results.
6. 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.
7. Can provide written informed consent.

Exclusion Criteria:

1. Extreme obesity, as defined by NIH Clinical Guidelines Body Mass Index (BMI \> 40)
2. Subjects who are pregnant or nursing or subjects planning to become pregnant in the first 24 months post-treatment.
3. Subjects with current or prior history of spinal infection at the symptomatic level.
4. Subjects with a diagnosis of severe osteoporosis with pathological fracture.
5. Radiofrequency ablation at the index level prior to injection in the past 3 months with positive results.
6. Any lumbar facet intra-articular injection including steroids at the index facet level prior to treatment injection in the past 3 months
7. Subjects that have undergone a procedure affecting the structure/biomechanics of the index facet joint or a spinal fusion adjacent to the symptomatic level.
8. Have undergone any procedure 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.
9. Clinically relevant instability on flexion-extension as determined by the primary investigator by overlaying films.
10. 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.
11. Presence of any of the following spinal deformities: spondylolysis at the corresponding facet level, spondylolisthesis \> grade II at the index facet.
12. Epidural steroid injections within 4 weeks prior to treatment injection.
13. Active malignancy or tumor as a source of symptoms or history of malignancy within the 5 years 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.
14. An elevated average baseline morphine equivalent dose, as determined by the investigator during screening consultation.
15. Taking systemic immunosuppressant medications or having a chronic, immunosuppressive state.
16. Taking anti-rheumatic disease medication (including methotrexate or other antimetabolites) within 3 months prior to study enrollment.
17. Clinically significant abnormal hematology.
18. Ongoing infectious disease, including but not limited to tuberculosis, HIV, hepatitis, and syphilis.
19. Unexplained fever, defined as greater than 100.4 degrees Fahrenheit or 38.0 degrees Celsius, or mental confusion at baseline.
20. Clinically significant cardiovascular, neurological, renal, hepatic or endocrine disease.
21. Participation in a study of an experimental drug or medical device for treatment of facet joint arthropathy within one year.
22. Any contraindication to MRI according to MRI guidelines or unwillingness to undergo fluoroscopic procedures.
23. History of or current evidence of alcohol or drug abuse or dependence, recreational use of illicit drug or prescription medications, or medical marijuana
24. 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.
25. Being involved in active litigation related to subject's low back pain.
26. Have a mental illness that could prevent completion of the study or protocol questionnaires.

Primary outcomes:
measure: Clinical assessment of nature, incidence, and severity of adverse events (AEs)
timeFrame: 24 months
measure: Self-reported assessment of nature, incidence, and severity of AEs
timeFrame: 24 months
measure: Study personnel assessment of nature, incidence, and severity of AEs
timeFrame: 24 months
Secondary outcomes:
measure: Global Health Scale (GHS)
timeFrame: 24 months
measure: Visual Analog Scale (VAS) - back and leg pain
timeFrame: 24 months
measure: Oswestry Disability Index (ODI)
timeFrame: 24 months
measure: Patient Health Questionnaire-4 (PHQ-4)
timeFrame: 24 months
measure: Narcotic Use Questionnaire
timeFrame: 24 months
measure: Work Status Questionnaire
timeFrame: 24 months
measure: PROMIS-CAT
timeFrame: 24 months
measure: Changes from Baseline evaluated by MRI
timeFrame: 24 months
measure: Change in number of red blood cells following treatment
timeFrame: 24 months
measure: Change in white blood cells with differential following treatment
timeFrame: 24 months
measure: Change in number of platelets following treatment
timeFrame: 24 months
measure: Change in Serum C-Reactive Protein (CRP)
timeFrame: 24 months
measure: Change in Erythrocyte Sedimentation Rate (ESR)
timeFrame: 24 months
measure: Change in Blood Urea Nitrogen (BUN)
timeFrame: 24 months
measure: Change in Creatinine
timeFrame: 24 months
measure: Change in Sodium
timeFrame: 24 months
measure: Change in Potassium
timeFrame: 24 months
measure: Change in Chloride
timeFrame: 24 months
measure: Change in Aspartate Aminotransferase (AST)
timeFrame: 24 months
measure: Change in Glucose
timeFrame: 24 months
measure: Change in Carbon Dioxide
timeFrame: 24 months
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
Study officials:
affiliation: Mayo Clinic
name: Wenchun Qu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: