Chronic Low Back Pain, Degenerative Disc Disease
Conditions
Brief summary
This is a randomized, comparative-effectiveness study comparing intradiscal autologous stem cells (from bone marrow aspirate) to intradiscal corticosteroid for the treatment of chronic discogenic low back pain (LBP). The primary objective of this study is to determine whether intradiscal autologous stem cells (from bone marrow aspirate) is more effective than intradiscal steroids for the treatment of chronic discogenic low back pain (LBP). Participants in this study will be randomized to receive up to intradiscal stem cell injections at 1 or 2 discs with cells harvested from a bone marrow aspirate drawn from participants' iliac crest, or an equal volume (2 mL) of intradiscal steroids and local anesthetic injected into the discs. In order to identify the painful disc(s), discography may be used at the discretion of the provider. Both treatments are frequently used as part of clinical care (i.e. there is no placebo group).
Detailed description
In this study, the investigators are attempting to determine if intradiscal injection of autologous bone marrow-derived mesenchymal stem cells (BMC) will decrease pain and improve function compared with intradiscal steroids. Up to 106 patients with a clinical diagnosis of chronic discogenic low back pain for greater than 6 months, MRI evidence of lumbar disc degeneration limited to one or two discs with \<50% disc height loss, and positive provocative discography (if clinically indicated) will be randomized to receive intradiscal BMC or steroid and long-acting local anesthetic (bupivacaine). Those randomized to group I will receive a 2 mL intradiscal injection of autologous bone marrow-derived mesenchymal stem cells from bone marrow aspirate of the posterior ilium, while those randomized to group II will receive an intradiscal injection of the steroid methylprednisolone and the local anesthetic bupivacaine. The first follow-up will occur at 4-weeks post-treatment at which time rescue medications may be prescribed or adjusted but no other analgesic interventions should occur. The primary outcome measure will be pain relief at 3 months post-treatment, while a positive categorical outcome will be a 2-point or greater decrease in average LBP coupled with either a score \> 5/7 on the PGIC (indicating noticeable improvement) or a 10-point decrease in ODI (indicating a clinically meaningful benefit). At 3 months, a repeat MRI will be obtained in selected patients at military treatment facilities (i.e. every 5th patient). Those who fail to experience a positive categorical outcome will be withdrawn from the study to receive alternate care, including an option for intradiscal BMC in those who received corticosteroid. For those who continue to experience a positive outcome, there will be 6- and 12-month follow up visits. At all follow-up visits, histories and physical exams will be performed and questionnaires assessing sleep, function, and anxiety and depression will be administered.
Interventions
In this intervention participants will receive a 2 mL intradiscal injection into each affected disc of autologous bone marrow-derived mesenchymal stem cells from bone marrow aspirate of the posterior ilium.
DRUGCorticosteroid
In this intervention participants will receive a 1 mL intradiscal injection of the steroid methylprednisolone (40 mg/mL) into each affected disc.
DRUGLocal anesthetic
In this intervention participants will receive a 1 mL intradiscal injection of the local anesthetic bupivacaine 0.5% into each affected disc.
Sponsors
The Geneva Foundation
United States Department of Defense
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
We are trying to determine whether intradiscal injection of autologous BMC (bone marrow-derived mesenchymal stem cells) will decrease pain and improve function compared with intradiscal steroid.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 2. Pain duration \> 6 months 3. Failure of non-operative treatment \> 3 months 4. Average pain score \> 4/10 over the past week 5. Presumed clinical diagnosis of discogenic low back pain (such as back\>leg pain, no or minimal radiation of pain past knee level, no significant improvement with epidural steroid injection, facet injections, sacroiliac joint injections and/or trigger point injections 6. Lumbar MRI within the last 18 months showing disc degeneration in \<= 2 lumbar discs; \<50% disc height loss in each disc 7. Patient agrees to have disc injection(s) and no other low back interventional or pharmacological treatments for at least 3 months 8. Patient agrees to be off all NSAIDs and corticosteroids from 2 weeks prior to and 3 months after the injection. 9. Stable dose of analgesic medications for at least 2 weeks
Exclusion criteria
1. Previous disc directed therapy involving heat (e.g. Intradiscal electrothermal therapy (IDET), biacuplasty) 2. Previous disc injection therapy in the last 3 months (e.g. corticosteroid, platelet rich plasma, stem cells) 3. Previous lumbar spine surgery (e.g. discectomy, fusion) at the affected levels (i.e. those with relief after surgery in whom adjacent segment discogenic pain is suspected can be considered on a case-by-case basis) 4. Disc extrusion or symptomatic disc protrusion at affected level 5. Untreated coagulopathy 6. Allergy to contrast dye or local anesthetics 7. Negative discography or discography showing \> 2 positive discs 8. Pain \> 15 years in duration 9. Opioid dose \> 30 mg oral morphine equivalents per day (patients may be tapered down or off opioids) 10. Diffuse pain phenotype (e.g. diagnosis of fibromyalgia) 11. Secondary gain (e.g. ongoing medical board or litigation related to injury) 12. Pregnancy (study subject report of negative pregnancy status will be sufficient to participate. Testing will be provided if subject is unsure or requests a test to confirm. 13. Cannot read or understand English
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean change in average low back pain score on 0-10 numerical rating scale | Baseline and 3 months | Mean change in average low back pain score over the past week at 3 months compared to baseline on 0-10 numerical rating scale (higher pain scores represent greater pain) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Athens Insomnia Scale score | 4 weeks | Scale measuring sleep dysfunction on an 8-question 0-24 scale, with higher numbers indicating greater dysfunction. |
| Patient global impression of change (PGIC) score | 4 weeks | 1-7 scale evaluating, with higher scores indicating greater improvement. |
| Oswestry disability index score | 4 weeks | 0-100% score measuring function for back and/ leg pain (higher scores indicate worse function) |
| Disc Degeneration based on MRI | 3 months | Disc degeneration on MRI (graded as significantly improved, slightly improved, no change, and worsening degeneration, based on Pfirmann's scale). |
| Hospital Anxiety and Depression Scale score | 4 weeks | 14-question scale measuring anxiety and depression, with each question scored as 0-3 (higher numbers represent greater anxiety or depression). |
| Mean change in worst low back pain score on 0-10 numerical rating scale | Baseline and 4 weeks | Mean change in worst low back pain score over the past week at week 4 compared to baseline on 0-10 numerical rating scale (higher pain scores represent greater pain). |
| Worst low back pain score on 0-10 numerical rating scale | 4 weeks | Worst low back pain score over the past week on 0-10 numerical rating scale (higher pain scores represent greater pain). |
| Positive categorical outcome | 4 weeks | Greater or equal to 2-point decrease in average low back pain score coupled with a PGIC score of 5 or higher or a decrease on Oswestry disability score of 10 or greater |
| Average low back pain score on 0-10 numerical rating scale | 4 weeks | Average low back pain score over the past week on 0-10 numerical rating scale (higher pain scores represent greater pain). |
Countries
United States
Outcome results
None listed