NCT03692221

Mesenchymal Stem Cells for Lumbar Degenerative Disc Disease

Percutaneous Image Guided Delivery of Autologous Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Symptomatic Degenerated Intervertebral Disc Disease

• Status: Withdrawn
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University Hospitals Cleveland Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Accepted

Summary

This study seeks to bridge these technologies and obtain data regarding the safety and efficacy of image guided percutaneous needle injection of expanded autologous bone marrow derived mesenchymal stem cells to symptomatic degenerated intervertebral discs in humans. The primary outcome will be to assess the safety and efficacy and monitor for adverse events.

Detailed description

Bone Marrow Aspiration and Cell Culture Procedure Utilizing fluoroscopic guidance, a coaxial needle will be advanced to the bone marrow space. The inner portion will be removed and 10-20mL of marrow aspirated. MSCs will be isolated and cultured in the Case Western Reserve University National Center for Regenerative Medicine/Seidman Cancer Center Cellular Therapy Lab using standard operating procedures established under the ongoing IND - as above. MSC Delivery/Transplantation Procedure Utilizing fluoroscopic guidance, a needle will be advanced to the outer annulus of the affected disc(s). Through the coaxial anchor, a needle will be advanced to the middle 1/3 of the disc, and confirmed in two planes (AP and lateral). On the day of infusion, MSCs will be transported from the Cellular Therapy Lab to the IR suite in a validated dry shipper. MSCs will be thawed in a 37ºC water bath and drawn into 1 ml syringes. Prior to delivery, an aliquot of the infused product will be tested for viability (trypan blue exclusion). Viability must be \>70% for cell transplantation. Treatment group one will receive an injection of 1-2 ml of a 2 x 106/ml concentration solution of MSCs and treatment group 2 will 1-2 ml of a 4 x 106/ml concentration solution of MSCs. Both treatment groups will be injected under intermittent fluoroscopic observation. A manometer will be used to monitor disc pressures, especially during MSC injection keeping pressure below 100 psi. Specifically, the volume of injectate will be determined based on three dynamic factors: real time imaging of contained contrast volume during discography, psi as measured during the injection (\< 100), and patient's symptoms (if patient's pain exceeds baseline, injection will be stopped) - up to a volume of 2cc of the assigned concentration. An aliquot of infused product will be submitted to the University Hospitals Cleveland Medical Center Microbiology Laboratory to test for microbiological contamination. In the event of a positive microbial test following administration of a cellular product: 1) The Principal Investigator and his/her designee will be notified and will notify the participant, 2) The contaminant will identified to a species level and antibiotic sensitivities determined, 3) The Medical Director of the Cellular Therapy Laboratory and/or the Principal Investigator will determine the best course of action based on the clinical situation. This may include blood cultures, administration of prophylactic antibiotics, and repeat cultures on the cell product. 4) An investigation to determine the source of the contamination will be conducted, and appropriate corrective measures will be undertaken. Finally, the adverse event will be reported to the IRB and FDA based on the respective federal and institutional reporting requirement, as well the approved data safety monitoring board charter. MRI/Quantitative MRI Procedure Routine images of the lumbar spine (sagittal and axial T1 and T2 weighted images) will be obtained for the purposes of: Monitoring for potential alternative effects of the cells including osteophyte formation, as well as any unexpected local outcome. In addition, a quantative MRI including fingerprinting. Magnetic resonance Fingerprinting (MRF) allows rapid and simultaneous quantification of T1and T2 relaxation times. The MRF sequence is based on varying multiple MR acquisition parameters \[ e.g. flip angle (FA) and time of repetition (TR)\] in a pseudorandom manner, such that unique signal evolutions called "fingerprints" are generated for each combination of tissue properties. These fingerprints are compared with a dictionary of simulated fingerprints generated for that sequence by a pattern matching process. Once there is a pattern match, the T1 and T2 values used to generate that dictionary entry are assigned to that voxel and used to create T1 and T2 maps that are perfectly anatomically co-registered. For spine, the proposed MRF sequence is based on a multislice Fast Imaging with Steady Precession (FISP) acquisition. Scanning will be done both in sagittal and axial planes using a multislice acquisition. The scan parameters are as follows: FOV: 400 mm, matrix 400 x 400 mm , TR/TE: 13-15 msec, in-plane resolution 1 x 1 mm, section thickness 5 mm, flip angle 5-75 degrees, acquisition time \~ 39 seconds per slice, with \~ 4 minutes scan time for a 5 slice sagittal image. In axial plane, the disc would be covered at each intervertebral level in 4-5 transverse slices and each axial acquisition would take \~ 3 minutes scan time. The MRF maps would be directly generated as DICOM images using Gadgetron online reconstruction. Image analysis would be done using a DICOM viewing software to draw Regions of Interest (ROIs) on nucleus pulposus for direct quantification of relaxation times. There is the capacity to generate MRF maps from raw data on Matlab which can also be used to draw ROIs for simultaneous quantification of T1 and T2 relaxation times. These values will be calculated on the pre and post treatment MRIs.

Conditions

• Disc Degeneration

Interventions

Type	Name	Description
DRUG	MSC Treatment group 1 (low dose)	Autologous Bone Marrow Derived Mesenchymal Stem Cells (MSC) - A one time injection of 1-2 ml of a 4 x 106/ml concentration solution
DRUG	MSC Treatment group 2 (high dose)	Autologous Bone Marrow Derived Mesenchymal Stem Cells (MSC) - A one time injection of 1-2 ml of a 4 x 106/ml concentration solution
OTHER	Healthy Control (no treatment)	Comparative analysis of psychometric and morphometric based data

Timeline

• Start date: 2019-06-01
• Primary completion: 2021-09-30
• Completion: 2022-09-30
• First posted: 2018-10-02
• Last updated: 2022-05-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study