Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Mesenchymal Stem Cells for Lumbar Degenerative Disc Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03692221
Recruitment Status : Not yet recruiting
First Posted : October 2, 2018
Last Update Posted : April 4, 2019
Sponsor:
Information provided by (Responsible Party):
Salim M Hayek, University Hospitals Cleveland Medical Center

Tracking Information
First Submitted Date  ICMJE September 24, 2018
First Posted Date  ICMJE October 2, 2018
Last Update Posted Date April 4, 2019
Estimated Study Start Date  ICMJE June 2019
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 28, 2018)
Rate of treatment related adverse events [ Time Frame: From baseline/randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year. ]
assessing for worsening of patients' baseline symptoms or functions (will be considered an AE); (also general AE events), particularly AE events related to the procedures/treatment. All AEs will be assessed by common terminology criteria for adverse events. .
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 2, 2018)
  • Changes in Pain -Visual Analogue Scale (VAS) for back pain [ Time Frame: Baseline, 1 month, 6 months and 1 year ]
    Temporal evaluation of pain before and after the procedure will be analyzed through documentation of Visual Analogue Scale of back pain (VAS). The VAS is a measurement instrument that tries to measure a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured. It is a unidimensional measure of pain intensity The instrument is presented by a straight horizontal line of fixed length, usually 100 mm. The ends are defined as the extreme limits of the parameter to be measured (symptom, pain, health) orientated from the left (worst) to the right (best). Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. No pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm) (11).
  • Changes in Pain - Oswestry Disability Index (ODI) scores over time [ Time Frame: Baseline, 1 month, 6 months and 1 year ]
    Temporal evaluation of pain before and after the procedure will be analyzed through documentation of Oswestry Disability Index (ODI) scores over time. Scoring - For each section the total possible score is 5: if the first statement is marked the section score = 0; if the last statement is marked, it = 5. If all 10 sections are completed the score is calculated. Interpretation scores go from minimal 0% disability to 100% disability.
  • changes in Quality of life - Short form Health Survey 36 (SF-36) [ Time Frame: Baseline, 1 month, 6 months and 1 year ]
    Temporal evaluation of quality of life before and after the procedure will be analyzed through documentation of SF36 quality of life questionnaire scores. Although this study is not cancer related, this questionnaire is a validated instrument for the evaluation of treatment related impact on quality of life - a critical outcome measure. Scoring - consisting of eight scaled scores which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
  • changes in MRI monitoring of transplant site [ Time Frame: Baseline and 1 year, if a subject were to withdraw prior to completion of the study and received MSC an MRI with be obtained. ]
    Magnetic resonance T2 mapping will be performed on all discs undergoing treatment for evaluation of potential quantitative, reproducible imaging change following treatment.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2018)
  • Changes in Pain -Visual Analogue Scale of back pain (VAS) [ Time Frame: Baseline, 1 month, 6 months and 1 year ]
    Temporal evaluation of pain before and after the procedure will be analyzed through documentation of Visual Analogue Scale of back pain (VAS). Scoring - A measurement instrument for subjective characteristics or attitudes that cannot be directly measured. Respondents specify their level of agreement to pain by indicating a position along a continuous line between two end-points.
  • Changes in Pain - Oswestry Disability Index (ODI) scores over time [ Time Frame: Baseline, 1 month, 6 months and 1 year ]
    Temporal evaluation of pain before and after the procedure will be analyzed through documentation of Oswestry Disability Index (ODI) scores over time. Scoring - For each section the total possible score is 5: if the first statement is marked the section score = 0; if the last statement is marked, it = 5. If all 10 sections are completed the score is calculated. Interpretation scores go from minimal 0% disability to 100% disability.
  • changes in Quality of life - Short form Health Survey 36 (SF-36) [ Time Frame: Baseline, 1 month, 6 months and 1 year ]
    Temporal evaluation of quality of life before and after the procedure will be analyzed through documentation of SF36 quality of life questionnaire scores. Although this study is not cancer related, this questionnaire is a validated instrument for the evaluation of treatment related impact on quality of life - a critical outcome measure. Scoring - consisting of eight scaled scores which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
  • changes in MRI monitoring of transplant site [ Time Frame: Baseline and 1 year, if a subject were to withdraw prior to completion of the study and received MSC an MRI with be obtained. ]
    Magnetic resonance T2 mapping will be performed on all discs undergoing treatment for evaluation of potential quantitative, reproducible imaging change following treatment.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mesenchymal Stem Cells for Lumbar Degenerative Disc Disease
Official Title  ICMJE Percutaneous Image Guided Delivery of Autologous Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Symptomatic Degenerated Intervertebral Disc Disease
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
24 participants will be equally randomized into two groups; 12 Healthy controls subjects & 12 treatment subjects. The treatment group will then be sub-divided and randomized into 6 subjects receiving a low dosage treatment and 6 subjects receiving a high dosage treatment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Disc Degeneration
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: MSC treatment group 1
    Low dose of Autologous Bone Marrow Derived Mesenchymal Stem Cells (MSC) -A one time injection of 1-2 ml of 2 x 106/ml concentrated solution
    Intervention: Drug: MSC Treatment group 1 (low dose)
  • Active Comparator: MSC treatment group 2
    High dose of Autologous Bone Marrow Derived Mesenchymal Stem Cells (MSC) -A one time injection of 1-2 ml of 4 x 106/ml concentrated solution
    Intervention: Drug: MSC Treatment group 2 (high dose)
  • Active Comparator: Healthy Control (no treatment)
    Comparative analysis of psychometric and morphometric based data
    Intervention: Other: Healthy Control (no treatment)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 28, 2018)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 30, 2022
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Symptoms despite conservative (non-surgical) management for > 6 months

    • Leg pain, if present, is of nonradicular origin, i.e., not due to stimulation of nerve roots or dorsal root ganglion of a spinal nerve by compressive forces.
    • Leg pain, if present, does not extend below the knee and is no greater than 50% of low back pain as measured on a visual analog scale. If bilateral leg pain existed, the worst leg pain is no greater than 50% of low back pain.
  • Diagnostic medical branch block or facet joint injection between 18 months and 2 weeks prior to the study procedure indicates no facet joint involvement.
  • Distress and risk assessment method stratification to a) normal or b) at risk designations
  • Modified Pfirrmann MR classification of implicated intervertebral discs of III, IV, or V
  • Absence of infection
  • Absence of coagulopathy
  • Ability to provide informed written consent

Exclusion Criteria:

  • Age > 80y or < 18 y
  • Neoplasia
  • History of recent or active malignancy(non-melanoma skin cancers, carcinoma in situ, etc. are allowable)
  • Active infection
  • Underlying congenital segmentation or other spinal anomalies that result in differential intervertebral disc pressures
  • Significant spinal stenosis

    • Interpreted as "severe" on any cross sectional imaging study
  • Pregnant or planning to become pregnant
  • Contraindication to MRI

    • Indwelling medical devices such as pacemakers, aneurysm clips, etc
    • Indwelling metal from any other cause (trauma, etc)

      • To be excluded with history and radiographs, as necessary
  • Immunosuppression
  • History or laboratory results indicative of any significant cardiac, endocrine, hematologic, hepatic, immunologic, infectious, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neoplastic, or other disorder that in the opinion of the Principal Investigator or his/her designee would preclude the safe performance of BM aspiration, transplantation of autologous MSCs, or performance of any of the planned study assessments.
  • Uncorrectable coagulopathies
  • Concurrent participation in another investigational trial involving systemic administration of agents or within the previous 30 days.
  • Extreme obesity, as defined by NIH Clinical Guidelines Body Mass Index (BMI >35).
  • Clinically relevant instability on flexion-extension as determined by the investigator by overlaying films.
  • Have undergone a previous surgery at the involved level that may have altered the target disc (e.g. discectomy, laminectomy, foraminotomy, fusion, intradiscal electrothermal therapy, intradiscal radiofrequency thermocoagulation etc.).
  • Have an acute fracture of the spine at the time of enrollment in the study. Clinically compromised vertebral bodies at the affected level due to current or past trauma, e.g., sustained pathological fracture or multiple fractures of vertebrae.
  • Have a history of epidural steroid injections within 1 week prior to study treatment.
  • Have received chronic (more than 7 consecutive days) treatment with systemic corticosteroids at a dose equivalent to prednisone ≥ 10 mg/day within 14 days prior to injection procedure.
  • Have received systemic or local nonsteroidal anti-inflammatory drugs (NSAIDS) injections into the index and/or adjacent vertebral levels within 48 hours prior to study procedure.
  • Have a known history of hypersensitivity or anaphylactic reaction to murine or bovine products or dimethyl sulfoxide (DMSO).
  • Have a known history of hypersensitivity or anaphylactic reaction to products from birds, such as feathers, eggs or poultry.
  • Have a positive screen for human immunodeficiency virus (HIV) by antibodies or nucleic acid test.
  • Have had treatment with any investigational therapy or device within 6 months of study procedure and/or plans to participate in any other allogeneic stem cell/progenitor cell therapy trial during the 3-year follow-up period.
  • Have been a recipient of prior stem cell/progenitor cell therapy or other biological intervention to repair the target intervertebral disc.
  • Are transient or has been treated in the last 6 months before enrollment for alcohol and/or drug abuse in an inpatient substance abuse program.
  • Habitual use of tobacco throughout the trial and follow-up.
  • Have a mental illness that could prevent completion of the study or protocol questionnaires. If subjects with psychiatric disease are stable, then they should be allowed to participate in the trial.
  • Neurological diseases including unstable diseases or disease which renders subjects unable to give informed consent which renders unable to give informed consent. (Subjects with well controlled epilepsy should not be excluded.)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Mario A Becerra, RN, BA 216) 844-1734 Mario.Becerra@UHhospitals.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03692221
Other Study ID Numbers  ICMJE 014924/0012/A002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Salim M Hayek, University Hospitals Cleveland Medical Center
Study Sponsor  ICMJE Salim M Hayek
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Melinda Lawrence, MD University Hospitals Cleveland Medical Center
PRS Account University Hospitals Cleveland Medical Center
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP