To determine the safety and feasibility of autologous, culture-expanded adipose-derived (AD) mesenchymal stromal cells (MSCs) in subjects with painful degenerative disc disease (DDD).
This study is a prospective, phase I dose-escalation study evaluating the safety and feasibility of intradiscally injected AD-MSCs in the treatment of painful degenerative disc disease. The investigators propose a blended open enrollment protocol of four cohorts, each comprised of 3 subjects, to allow for interim analysis following the completion of each cohort to review safety data prior to commencing treatment of the next cohort. A total of 12 subjects will be enrolled. Subjects will be screened at outpatient clinic visit appointments and interested qualified subjects will be consented and offered participation in this trial. Once consent has been obtained baseline values will be established and subjects will begin treatment and follow-up for the next 24 months. Baseline data will include physical examination of the axial skeleton and sacroiliac region, neurologic examination, clinical assessment of low back pain and function using validated Patient Reported Outcome Measures (PROMs), radiographs, peripheral blood analysis, and MRI imaging. Abdominal fat will be harvested through a small incision and processed by the Mayo Clinic IMPACT laboratory using current Good Manufacturing Practices (cGMPs) and previously established standard operating procedures (SOPs) to produce clinical grade, autologous, culture-expanded AD-MSCs for subsequent intradiscal injection. All injections will be performed using fluoroscopic guidance and all patients will be clinically evaluated immediately after procedure and at week 2 and 4 post-treatment to assess for acute adverse events (AEs). Following completion of their respective treatment cycle, each subject will be followed for study endpoints using a predetermined protocol, including clinical evaluation, radiography, MRI, and peripheral blood analysis. A final visit for evaluation and imaging will be conducted at the end of the study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Human, autologous, culture expanded, adipose-derived, mesenchymal stromal cells (AMSCs) produced on site in the Mayo Clinic Immune Progenitor and Cell Therapeutics Laboratory using current good manufacturing practices (cGMPs).
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Number of patients who experience adverse events (AEs)
An adverse event is 1) Defined as any untoward or undesirable medical occurrence in the form of signs, symptoms, abnormal findings, or diseases that emerge or worsen relative to baseline during the study regardless of causal relationship.
Time frame: 2 years post final injection
Change in low back pain and function following injection of AD-MSCs
Change in low back pain will be measured by a 10 cm visual analog scale (VAS) score, with one end of the scale 0 indicating no pain, and the other end 10 indicating the worst pain ever.
Time frame: Baseline, treatment day, 2 weeks, 4 weeks, 3 months, 6 months, 12 months, 18 months, 24 months
Change in low back pain and function following injection of AD-MSCs
Change in low back pain and function will be measured by Global Health Scale (GHS) which includes health related questions with Likert Scales of 1 to 5, or 1 to 10. Based on the question, 1 may indicate a higher amount, or lower amount for the measured variable.
Time frame: Baseline, treatment day, 2 weeks, 4 weeks, 3 months, 6 months, 12 months, 18 months, 24 months
Change in low back pain and function following injection of AD-MSCs
Change in low back pain and function will be measured by Oswestry Disability Index (ODI), which contains 10 questions about daily activities with scores ranging from 0 to 5, where 0 indicates no difficulty/disability, and 5 indicates the most severe difficulty/disability. The final score is multiplied by 2 to give a final score from 0 to 100, where 0 is no difficulty/disability and 100 is severe difficulty/disability.
Time frame: Baseline, treatment day, 2 weeks, 4 weeks, 3 months, 6 months, 12 months, 18 months, 24 months
Change in low back pain and function following injection of AD-MSCs
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Change in low back pain and function will be measured by Quality of Life (SF-36 questionnaire, which has questions regarding health and activity scored from 1 to 3, 1 to 5, or yes/no (1 to 2). Based on the question, 1 may indicate a lower amount/frequency or higher amount/frequency.
Time frame: Baseline, treatment day, 2 weeks, 4 weeks, 3 months, 6 months, 12 months, 18 months, 24 months
Change in low back pain and function following injection of AD-MSCs
Change in low back pain and function will be measured by Narcotic Use Questionnaire, which includes questions regarding the current use of narcotics (yes/no) and how long participants have used narcotics for pain relief (days, months, years).
Time frame: Baseline, treatment day, 2 weeks, 4 weeks, 3 months, 6 months, 12 months, 18 months, 24 months
Changes from Baseline in disc height index as measured by X-ray at 12 months and 24 months
An x-ray will be performed using standard radiography technology and interpreted by a trained radiologist.
Time frame: Baseline, 12 Months, 24 Months
Changes from Baseline in T2 weighted signal intensity of the Nucleus Pulposus (NP) as measured by MRI without contrast
Images will be obtained by MRI and interpreted by a trained radiologist.
Time frame: Baseline, 6 Months, 12 Months, 24 Months