A Phase I Study Evaluating the Safety and Feasibility of Autologous, Culture-Expanded Adipose-Derived Mesenchymal Stromal Cells in Subjects With Painful Degenerative Disc Disease
Overview
- Phase
- Phase 1
- Intervention
- Autologous Adipose-Derived Mesenchymal Stromal Cells
- Conditions
- Degenerative Disc Disease
- Sponsor
- Mayo Clinic
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- Number of patients who experience adverse events (AEs)
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
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).
Detailed Description
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.
Investigators
Wenchun Qu
M.D., M.S., Ph.D.
Mayo Clinic
Eligibility Criteria
Inclusion Criteria
- •Male or female subjects 18 years of age and older
- •Persons of childbearing potential must be non-nursing and have a negative serum pregnancy test prior to receiving the study drug 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. 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 outcome. Any serious adverse events (SAEs) associated with pregnancy will be recorded. The requirement for radiation (X-ray, MRI) will be removed.
- •Moderate radiographic degeneration of an Intervertebral Disc (IVD) from L1 to S1, with a disc suspected of causing chronic low back pain. Chronic low back pain is defined as the following:
- •Low back pain for at least 6 months
- •Failed at least 3 months of conservative back pain care. Conservative treatment regimens may include any or all of the following: initial rest, medications e.g., anti-inflammatory, analgesics, narcotics/opioids, muscle relaxants, massage, acupuncture, osteopathic or chiropractic manipulations, activity modification, home-directed lumbar exercise program, and non-invasive pain control treatments or procedures
- •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 30mm and not more than 90mm of 100mm on low back pain VAS (average pain over 24 hours)Radicular leg pain ≤20mm in both legs on a 100mm VAS scale
- •Oswestry Disability Index (ODI) score of at least 20 and no more than 90 on a 100 point scale.
- •Patients must demonstrate radiographic evidence of mild to moderate degenerative disc disease as defined by radiographic evidence of modified Pfirrmann scores of 3, 4, 5 or 6 on MRI at the index disc. With respect to inclusion criteria, DDD is defined as radiographic evidence of change from normal disc morphology of the index disc identified by modified Pfirrmann score and Modic Type I or II changes.
Exclusion Criteria
- •Subjects who are pregnant or nursing, or subjects planning to become pregnant in the first 24 months post-treatment. If a subject becomes pregnant during the study, the subject will remain in the study and only the requirement for radiation (x-ray or MRI) will be removed.
- •Extreme obesity, as defined by NIH Clinical Guidelines Body Mass Index (BMI \> 40)
- •Have undergone a surgical procedure (e.g. discectomy, intradiscal electrothermal therapy, intradiscal radiofrequency, artificial disc replacement, interbody fusion) on the disc at the index or adjacent level
- •Osteoporosis, as defined by dual-energy X-ray absorptiometry (DEXA) scan. A DEXA T-score of ≤ -2.5 will exclude the subject. The following at-risk subjects will be required to undergo a DEXA scan at screening:
- •Female subjects with a Simple Calculated Osteoporosis Risk Estimation (SCORE) of ≥6 and male subjects with a Male Osteoporosis Risk Estimation Score (MORES) of ≥6
- •Females ≥50 years of age or who are post-menopausal or post-hysterectomy with oophorectomy
- •Subjects taking bisphosphonate medications for the treatment of osteoporosis
- •Subjects with a history of chronic, high-dose steroid use (oral and/or inhaled). High-dose steroid use is defined as:
- •i. Daily, chronic use of oral steroids of ≥5 mg/day
- •ii. Daily, chronic use of inhaled corticosteroids (at least twice per day)
Arms & Interventions
5×10^6 AD-MSCs
Subjects will receive one injection of 5 million Autologous Adipose-Derived Mesenchymal Stromal Cells
Intervention: Autologous Adipose-Derived Mesenchymal Stromal Cells
20×10^6 AD-MSCs
Subjects will receive one injection of 20 million Autologous Adipose-Derived Mesenchymal Stromal Cells
Intervention: Autologous Adipose-Derived Mesenchymal Stromal Cells
Outcomes
Primary Outcomes
Number of patients who experience adverse events (AEs)
Time Frame: 2 years post final injection
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.
Secondary Outcomes
- Change in low back pain and function following injection of AD-MSCs(Baseline, treatment day, 2 weeks, 4 weeks, 3 months, 6 months, 12 months, 18 months, 24 months)
- Changes from Baseline in T2 weighted signal intensity of the Nucleus Pulposus (NP) as measured by MRI without contrast(Baseline, 6 Months, 12 Months, 24 Months)
- Changes from Baseline in disc height index as measured by X-ray at 12 months and 24 months(Baseline, 12 Months, 24 Months)