Disc DegenerationEarly Phase 1NCT03692221
Mesenchymal Stem Cells for Lumbar Degenerative Disc Disease
A Early Phase 1 study testing MSC Treatment group 1 (low dose) and MSC Treatment group 2 (high dose) in people with Disc Degeneration, run by University Hospitals Cleveland Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Disc Degeneration
- What is being tested?
- MSC Treatment group 1 (low dose) and MSC Treatment group 2 (high dose)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2019to 30 Sep 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Absence of infection
- Absence of coagulopathy
- Ability to provide informed written consent
Who cannot join
- 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
Show all 32Show fewer
- 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.)
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
About this study
Official title: Percutaneous Image Guided Delivery of Autologous Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Symptomatic Degenerated Intervertebral Disc Disease
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.
Read the 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
- Being tested
- MSC Treatment group 1 (low dose), MSC Treatment group 2 (high dose), Healthy Control (no treatment)
- Keywords
- Back pain
- Medical subject headings
- Intervertebral Disc Degeneration, Back Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSC Treatment group 1 (low dose)Drug
Autologous Bone Marrow Derived Mesenchymal Stem Cells (MSC) - A one time injection of 1-2 ml of a 4 x 106/ml concentration solution
MSC Treatment group 2 (high dose)Drug
Autologous Bone Marrow Derived Mesenchymal Stem Cells (MSC) - A one time injection of 1-2 ml of a 4 x 106/ml concentration solution
Healthy Control (no treatment)Other
Comparative analysis of psychometric and morphometric based data
| Study group | Role | What they receive |
|---|---|---|
| MSC treatment group 1 | Experimental | 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 Receives: Drug: MSC Treatment group 1 (low dose) |
| MSC treatment group 2 | Active comparator | 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 Receives: Drug: MSC Treatment group 2 (high dose) |
| Healthy Control (no treatment) | Active comparator | Comparative analysis of psychometric and morphometric based data Receives: Other: Healthy Control (no treatment) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of treatment related adverse events
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. .
Measured: 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.
Secondary outcomes (4)
Changes in Pain -Visual Analogue Scale (VAS) for back pain
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).
Measured: Baseline, 1 month, 6 months and 1 year
Changes in Pain - Oswestry Disability Index (ODI) scores over time
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.
Measured: Baseline, 1 month, 6 months and 1 year
changes in Quality of life - Short form Health Survey 36 (SF-36)
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.
Measured: Baseline, 1 month, 6 months and 1 year
changes in MRI monitoring of transplant site
Magnetic resonance T2 mapping will be performed on all discs undergoing treatment for evaluation of potential quantitative, reproducible imaging change following treatment.
Measured: Baseline and 1 year, if a subject were to withdraw prior to completion of the study and received MSC an MRI with be obtained.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2018
- Study startJun 2019 (estimated)
- Primary completion30 Sep 2021 (estimated)
- Study completion30 Sep 2022 (estimated)
Why it stopped: Stalled due to Covid
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (98)Papers the sponsor has linked to this study.
- Other trials for Disc DegenerationStudies of the same condition, open and under way.
- More trials run by University Hospitals Cleveland Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Cleveland Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Salim M Hayek, University Hospitals Cleveland Medical Center
- Investigators
- Melinda Lawrence, MD, Principal investigator, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03692221
- Sponsor's protocol ID
- 014924/0012/A002
- Status last verified
- Apr 2022
- First submitted
- 24 Sep 2018
- Last updated
- 5 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Walker J 3rd, El Abd O, Isaac Z, Muzin S. Discography in practice: a clinical and historical review. Curr Rev Musculoskelet Med. 2008 Jun;1(2):69-83. doi: 10.1007/s12178-007-9009-9.
PubMed 19468876Frymoyer JW, Cats-Baril WL. An overview of the incidences and costs of low back pain. Orthop Clin North Am. 1991 Apr;22(2):263-71.
PubMed 1826550Cheung KM, Karppinen J, Chan D, Ho DW, Song YQ, Sham P, Cheah KS, Leong JC, Luk KD. Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine (Phila Pa 1976). 2009 Apr 20;34(9):934-40. doi: 10.1097/BRS.0b013e3181a01b3f.
PubMed 19532001Madigan L, Vaccaro AR, Spector LR, Milam RA. Management of symptomatic lumbar degenerative disk disease. J Am Acad Orthop Surg. 2009 Feb;17(2):102-11. doi: 10.5435/00124635-200902000-00006.
PubMed 19202123Bogduk N, Karasek M. Two-year follow-up of a controlled trial of intradiscal electrothermal anuloplasty for chronic low back pain resulting from internal disc disruption. Spine J. 2002 Sep-Oct;2(5):343-50. doi: 10.1016/s1529-9430(02)00409-6.
PubMed 14589465Kvarstein G, Mawe L, Indahl A, Hol PK, Tennoe B, Digernes R, Stubhaug A, Tonnessen TI, Beivik H. A randomized double-blind controlled trial of intra-annular radiofrequency thermal disc therapy--a 12-month follow-up. Pain. 2009 Oct;145(3):279-286. doi: 10.1016/j.pain.2009.05.001. Epub 2009 Aug 3.
PubMed 19647940Freeman BJ, Fraser RD, Cain CM, Hall DJ, Chapple DC. A randomized, double-blind, controlled trial: intradiscal electrothermal therapy versus placebo for the treatment of chronic discogenic low back pain. Spine (Phila Pa 1976). 2005 Nov 1;30(21):2369-77; discussion 2378. doi: 10.1097/01.brs.0000186587.43373.f2.
PubMed 16261111Williams JD, P.K., ed. Lower Back Pain and Disorders of Intervertebral Discs. 11 ed. Campbell's Operative Orthopaedics., ed. C.a. Beaty. 2007, Mosby.
Hilibrand AS, Robbins M. Adjacent segment degeneration and adjacent segment disease: the consequences of spinal fusion? Spine J. 2004 Nov-Dec;4(6 Suppl):190S-194S. doi: 10.1016/j.spinee.2004.07.007.
PubMed 15541666Nesti LJ, Li WJ, Shanti RM, Jiang YJ, Jackson W, Freedman BA, Kuklo TR, Giuliani JR, Tuan RS. Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam. Tissue Eng Part A. 2008 Sep;14(9):1527-37. doi: 10.1089/ten.tea.2008.0215.
PubMed 18707229Shuff C, An HS. Artificial disc replacement: the new solution for discogenic low back pain? Am J Orthop (Belle Mead NJ). 2005 Jan;34(1):8-12.
PubMed 15707133Solchaga LA, Penick K, Goldberg VM, Caplan AI, Welter JF. Fibroblast growth factor-2 enhances proliferation and delays loss of chondrogenic potential in human adult bone-marrow-derived mesenchymal stem cells. Tissue Eng Part A. 2010 Mar;16(3):1009-19. doi: 10.1089/ten.TEA.2009.0100.
PubMed 19842915Wang F, Dennis JE, Awadallah A, Solchaga LA, Molter J, Kuang Y, Salem N, Lin Y, Tian H, Kolthammer JA, Kim Y, Love ZB, Gerson SL, Lee Z. Transcriptional profiling of human mesenchymal stem cells transduced with reporter genes for imaging. Physiol Genomics. 2009 Mar 3;37(1):23-34. doi: 10.1152/physiolgenomics.00300.2007. Epub 2008 Dec 30.
PubMed 19116247Love Z, Wang F, Dennis J, Awadallah A, Salem N, Lin Y, Weisenberger A, Majewski S, Gerson S, Lee Z. Imaging of mesenchymal stem cell transplant by bioluminescence and PET. J Nucl Med. 2007 Dec;48(12):2011-20. doi: 10.2967/jnumed.107.043166. Epub 2007 Nov 15.
PubMed 18006616Welter JF, Solchaga LA, Penick KJ. Simplification of aggregate culture of human mesenchymal stem cells as a chondrogenic screening assay. Biotechniques. 2007 Jun;42(6):732, 734-7. doi: 10.2144/000112451.
PubMed 17612296
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Percutaneous Image Guided Delivery of Autologous Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Symptomatic Degenerated Intervertebral Disc Disease
- ClinicalTrials.gov ID
- NCT03692221
- Acronym / sponsor ID
- 014924/0012/A002
- Conditions
- Disc Degeneration
- Keywords
- Back pain
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Stalled due to Covid
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospitals Cleveland Medical CenterUniversity, hospital or other
- Study start
- Jun 2019 (estimated)
- Primary completion
- 30 Sep 2021 (estimated)
- Study completion
- 30 Sep 2022 (estimated)
- First posted
- 2 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- 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
| Arm | Type | Receives |
|---|---|---|
| MSC treatment group 1 | Experimental | Drug: MSC Treatment group 1 (low dose)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 |
| MSC treatment group 2 | Active comparator | Drug: MSC Treatment group 2 (high dose)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 |
| Healthy Control (no treatment) | Active comparator | Other: Healthy Control (no treatment)Comparative analysis of psychometric and morphometric based data |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Symptoms despite conservative (non-surgical) management for > 6 months
- 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
Key exclusion criteria (32 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 1 |
| 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 | Drug | MSC treatment group 2 |
| Healthy Control (no treatment)Comparative analysis of psychometric and morphometric based data | Other | Healthy Control (no treatment) |
Primary outcome
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. .
4 secondary outcomes
Changes in Pain -Visual Analogue Scale (VAS) for back pain
Time frame: Baseline, 1 month, 6 months and 1 year
Changes in Pain - Oswestry Disability Index (ODI) scores over time
Time frame: Baseline, 1 month, 6 months and 1 year
changes in Quality of life - Short form Health Survey 36 (SF-36)
Time frame: Baseline, 1 month, 6 months and 1 year
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2022.
- Background: PubMed 19468876Walker J 3rd, El Abd O, Isaac Z, Muzin S. Discography in practice: a clinical and historical review. Curr Rev Musculoskelet Med. 2008 Jun;1(2):69-83. doi: 10.1007/s12178-007-9009-9.
- Background: PubMed 1826550Frymoyer JW, Cats-Baril WL. An overview of the incidences and costs of low back pain. Orthop Clin North Am. 1991 Apr;22(2):263-71.
- Background: PubMed 19532001Cheung KM, Karppinen J, Chan D, Ho DW, Song YQ, Sham P, Cheah KS, Leong JC, Luk KD. Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine (Phila Pa 1976). 2009 Apr 20;34(9):934-40. doi: 10.1097/BRS.0b013e3181a01b3f.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melinda Lawrence, MD principal investigator
University Hospitals Cleveland Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing MSC Treatment group 1 (low dose) and MSC Treatment group 2 (high dose) in people with Disc Degeneration, run by University Hospitals Cleveland Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03692221, which also lists 98 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2022.