Clinical trial NCT04735185: Stem Cells vs. Steroids for Discogenic Back Pain
Official title: Randomized, Comparative-effectiveness Study of Intradiscal Autologous Bone Marrow Concentrate Versus Intradiscal Corticosteroid for Chronic Discogenic Low Back Pain
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Chronic Low Back Pain
Degenerative Disc Disease
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: The Geneva Foundation
name: United States Department of Defense
First posted: 2021-02-03
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean change in average low back pain score on 0-10 numerical rating scale
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Hospital Anxiety and Depression Scale score
timeFrame: 4 weeks
measure: Hospital Anxiety and Depression Scale score
timeFrame: 3 months
measure: Hospital Anxiety and Depression Scale score
timeFrame: 6 months
measure: Hospital Anxiety and Depression Scale score
timeFrame: 1 year
measure: Athens Insomnia Scale score
timeFrame: 4 weeks
measure: Athens Insomnia Scale score
timeFrame: 3 months
measure: Athens Insomnia Scale score
timeFrame: 6 months
measure: Athens Insomnia Scale score
timeFrame: 1 year
measure: Patient global impression of change (PGIC) score
timeFrame: 4 weeks
measure: Patient global impression of change (PGIC) score
timeFrame: 3 months
measure: Patient global impression of change (PGIC) score
timeFrame: 6 months
measure: Patient global impression of change (PGIC) score
timeFrame: 1 year
measure: Oswestry disability index score
timeFrame: 4 weeks
measure: Oswestry disability index score
timeFrame: 3 months
measure: Oswestry disability index score
timeFrame: 6 months
measure: Oswestry disability index score
timeFrame: 1 year
measure: Disc Degeneration based on MRI
timeFrame: 3 months
measure: Average low back pain score on 0-10 numerical rating scale
timeFrame: 4 weeks
measure: Average low back pain score on 0-10 numerical rating scale
timeFrame: 3 months
measure: Average low back pain score on 0-10 numerical rating scale
timeFrame: 6 months
measure: Average low back pain score on 0-10 numerical rating scale
timeFrame: 1 year
measure: Mean change in worst low back pain score on 0-10 numerical rating scale
timeFrame: Baseline and 4 weeks
measure: Mean change in worst low back pain score on 0-10 numerical rating scale
timeFrame: Baseline and 3 months
measure: Mean change in worst low back pain score on 0-10 numerical rating scale
timeFrame: Baseline and 6 months
measure: Mean change in worst low back pain score on 0-10 numerical rating scale
timeFrame: Baseline and 1 year
measure: Worst low back pain score on 0-10 numerical rating scale
timeFrame: 4 weeks
measure: Worst low back pain score on 0-10 numerical rating scale
timeFrame: 3 months
measure: Worst low back pain score on 0-10 numerical rating scale
timeFrame: 6 months
measure: Worst low back pain score on 0-10 numerical rating scale
timeFrame: 12 months
measure: Positive categorical outcome
timeFrame: 4 weeks
measure: Positive categorical outcome
timeFrame: 3 months
measure: Positive categorical outcome
timeFrame: 6 months
measure: Positive categorical outcome
timeFrame: 12 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Steven Cohen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pettine KA, Murphy MB, Suzuki RK, Sand TT. Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells. 2015 Jan;33(1):146-56. doi: 10.1002/stem.1845.
citation: Noriega DC, Ardura F, Hernandez-Ramajo R, Martin-Ferrero MA, Sanchez-Lite I, Toribio B, Alberca M, Garcia V, Moraleda JM, Sanchez A, Garcia-Sancho J. Intervertebral Disc Repair by Allogeneic Mesenchymal Bone Marrow Cells: A Randomized Controlled Trial. Transplantation. 2017 Aug;101(8):1945-1951. doi: 10.1097/TP.0000000000001484.