Overview
This is an open-label, single-center Phase I/II clinical trial investigating the safety and efficacy of autologous nucleus pulposus cells (aNPC) in patients with disc degeneration. Eligible participants are those assessed by the principal investigator to have disc herniation suitable for discectomy and confirmed disc degeneration. During the treatment period, participants will receive a single injection of autologous nucleus pulposus cells at a concentration of approximately 1×10⁶ viable cells/mL with a total volume not exceeding 3 mL. The injection will be guided by C-arm X-ray to ensure accurate placement into the degenerated central nucleus pulposus of the disc from which tissue was previously harvested. Participants will be followed for 12 months. Safety assessments will primarily include monitoring for inflammatory responses using ESR and CRP after cell injection, as well as recording any treatment-emergent adverse events (AEs). Efficacy will be evaluated using pain assessment and imaging outcomes, including lumbar X-ray and MRI reviewed independently by a radiologist. Additionally, patient-reported outcomes will assess quality of life improvements following treatment using the Visual Analogue Scale (VAS), Activities of Daily Living (ADLs), and the Oswestry Disability Index (ODI). Laboratory tests, including CBC/DC, BUN, creatinine, AST, and ALT, will also be conducted throughout the treatment and observation period to monitor participant safety.
Description
Degenerative disc disease (DDD) commonly occurs in adults and represents an irreversible aging process. It is also one of the primary causes of low-back pain (LBP). The nucleus pulposus possesses high water-retention capacity, allowing it to cushion the vertebrae and reduce friction during movement. However, with aging, the disc gradually loses its water absorption ability and becomes fibrotic, leading to structural degeneration. In addition, sports injuries or sudden mechanical stress may cause disc herniation, compressing spinal nerves and triggering both disc degeneration and back pain. The release of inflammatory mediators further induces severe pain. Once the nucleus pulposus herniates, the tissue continues to degenerate, placing greater stress on the surrounding annulus fibrosus. Over time, this accelerates the progression of DDD.
Regenerative medicine has recently emerged as a promising clinical treatment approach, aiming to restore or rebuild healthy tissue through biological means, with cell therapy being a key area of development. In our approach, autologous cells are harvested from patients' tissue, expanded and activated through ex vivo cell culture, and then reintroduced into the degenerated disc region under X-ray guidance. This autologous cell therapy avoids the risk of immune rejection or transplant-related complications. For patients undergoing treatment for disc herniation, discectomy not only relieves pain symptoms but also provides herniated disc tissue as an ideal source of autologous disc cells for further use in regenerative therapy. These cells can serve as a valuable implant material for disc repair.
The current clinical trial enrolls both male and female subjects aged ≥20 years who have not undergone prior disc surgery. Eligible patients must be diagnosed with disc herniation and scheduled for discectomy, during which nucleus pulposus tissue will be collected for cell culture. Following cell expansion, the cultured cells will be reintroduced into the degenerated disc region via injection. Subjects will undergo multiple follow-up visits within one year after surgery to evaluate safety and efficacy, supplemented with imaging studies to assess disc height, tissue regeneration, and water-retention capacity. Hence, the primary objective of this study is to evaluate the safety of aNPC during the treatment of disc degeneration. Secondary objectives include evaluating the effects of these cells on subjects' quality of life, as measured by Activities of Daily Living (ADLs) and the Oswestry Disability Index (ODI), on pain improvement assessed by the Visual Analogue Scale (VAS), and on imaging outcomes, including lumbar X-ray and MRI assessments, before and after treatment.
This clinical study will be conducted in accordance with the requirements of the Institutional Review Board (IRB) and will fully comply with Good Clinical Practice (GCP) standards and relevant regulations to minimize patient safety risks. In the future, this therapy has the potential to reduce the long-term reliance on pain medications, avoid associated side effects, slow disc degeneration, and alleviate pain and discomfort. Furthermore, it is expected to decrease the need for surgical interventions and provide a more effective and convenient therapeutic option for patients suffering from degenerative disc disease.
Eligibility
Inclusion Criteria:
- Main inclusion criteria:
- Age≧20 years old.
- Diagnosed with a disc herniation, can be having a discectomy.
- Having low back pain with affecting the lower limbs.
- Lower back pain should persist for more than six weeks and fail to improve with conservative treatments.
- VAS score ≥ 6.
- Single lumbar intervertebral disc degeneration or ruptured pinched nerve evaluated by Lumbar X-ray and MRI.
- Informed consent has been signed by subjects of his own accord.
Exclusion Criteria:
- 2\. Main exclusion criteria:
- Levels of coagulation, liver, and kidney functions do not meet reference ranges. Following the reference range announced by the medical laboratory department at clinical trial institution, as shown below, PT/INR: 11-15 (sec)/ INR 0.78-1.12; BUN: 6.0-20.0 (mg/dL); Creatinine: (Female)0.5-0.9 (mg/dL)/ (Male)0.7-1.2 (mg/dL); AST (GOT): \< 40 (U/L); ALT (GPT): \< 41 (U/L)
- Bone marrow function did not meet specific criteria, including appropriate levels of white blood cells, platelets, and hemoglobin.
Following the reference range announced by the medical laboratory department at clinical trial institution, as shown below, White blood cells: 4.00-11.00 (\103/μL); Platelets: 130-140 (\103/μL); Hemoglobin: Female: 12.0-16.0 (g/dL), Male: 13.0-17.0 (g/dL)
- Spinal inflammation, injury, or structural instability, including but not limited to the following：spondylodiscitis, spondylitis, spondylolisthesis, fracture, previous spinal trauma, severe spinal canal stenosis (hypertrophic fibrosis or ossification oof the ligamentum flavum), spinal tumor, metabolic bone disease.
- Local tissue infection or inflammation near the surgical site.
- Systemic infections require antibiotic treatment.
- Immunodeficiency disease or current use of immunosuppressive drugs.
- Tumor history.
- Severely degenerated or damaged annulus fibrosis, and the Pfirrman grade exceeds V.
- Hypersensitivity to penicillin, streptomycin, and amphotericin B or similar antibiotics.
- Cannot undergo discectomy.
- Autoimmune disease.
- Blood disease. (ex, anemia, blood coagulation dysfunction, leukemia, ITP, etc.)
- Spinal surgical treatment received.
- Drug allergy.
- Have been enrolled in other clinical trials in the past four weeks.
- Pregnancy and breastfeeding.
- Positive for HIV or VDRL in blood tests, as well as uncontrolled carriers of hepatitis B or C.
- Cannot take an MRI scan.
- Subjects who are not suitable for participating in this clinical trial diagnosed by PI.
