Autologous, Culture-Expanded Mesenchymal Stromal Cells for Degenerative Disc Disease

NCT03461458 | Terminated Phase 1 FDA Drug

• 1 other identifier: 17-002136
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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).

Conditions

Degenerative Disc Disease

Keywords

Degenerative Disc Disease; Musculoskeletal Diseases; Lumbar

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years post final injection

Secondary Outcomes (7)

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

5×10^6 AD-MSCs

EXPERIMENTAL

Subjects will receive one injection of 5 million Autologous Adipose-Derived Mesenchymal Stromal Cells

Drug: Autologous Adipose-Derived Mesenchymal Stromal Cells

20×10^6 AD-MSCs

EXPERIMENTAL

Subjects will receive one injection of 20 million Autologous Adipose-Derived Mesenchymal Stromal Cells

Drug: Autologous Adipose-Derived Mesenchymal Stromal Cells

Interventions

Autologous Adipose-Derived Mesenchymal Stromal Cells DRUG

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).

Also known as: AMSCs

20×10^6 AD-MSCs; 5×10^6 AD-MSCs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Change from normal disc morphology of the index disc will be determined based on radiographic evaluation. Radiographs must show all of the following as determined by participating fellowship trained radiologists at Mayo Clinic:
• A modified Pfirrmann score of 3, 4, 5 or 6 on MRI at the index disc
• Modic Grade II changes or less on MRI at the index disc
• With or without contained disc protrusion at the index disc on MRI
• 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 is present, the worst leg pain is no greater than 50% of low back pain.

You may not qualify if:

• 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)
• iii. Use of short-term (less than 10 days) oral steroids at a daily dose \>20mg prednisone (or equivalent ) within 1 month of study procedure
• Any lumbar intradiscal injection, including steroids, into the index or adjacent discs prior to treatment injection, with the exception of the following injections performed at least 2 weeks prior to study treatment:
• i. Contrast medium (discography or other diagnostic injection)
• ii. Nerve-blocking anesthetics (e.g., lidocaine, bupivacaine)
• iii. Antibiotics

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Intervertebral Disc Degeneration; Musculoskeletal Diseases

Condition Hierarchy (Ancestors)

Spinal Diseases; Bone Diseases

Study Officials

• Wenchun Qu, MD, MS, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., M.S., Ph.D.

Study Record Dates

• First Submitted: February 13, 2018
• First Posted: March 12, 2018
• Study Start: October 17, 2018
• Primary Completion: February 6, 2021
• Study Completion: February 6, 2021
• Last Updated: January 25, 2022

Record last verified: 2022-01

Locations

US (1)