This preliminary study was designed to evaluate the clinical effectiveness of intradiskal autologous PRP for a subset of participants with chronic lumbar diskogenic pain. To our knowledge, this is one of the first clinical studies investigating the efficacy of an intradiskal cell therapy in a double-blind, randomized controlled study design.
The strengths of this study were its double-blind, randomized, controlled trial design, the rigorous participant selection process, the high follow-up rate, and long term data (ie, at least 1 year) in the majority of participants. Although the number of participants was relatively low, this study detected statistically significant improvements in NRS Best Pain, FRI, and NASS satisfaction between the treatment and control groups over 8 weeks. In addition, the beneficial effects of PRP were sustained for at least 1 year with respect to the FRI Index. No participant in the treatment group experienced complications, including progressive disk herniation, neurologic injury, or disk space infection.
Meticulous participant selection was critical for the study. Inclusion and exclusion criteria were rigorous, thus explaining the 4-year time period necessary to enroll 51 eligible participants. Among the authors, it was agreed that PRP is a targeted annular therapy. If the disk protrusion was significant (>5 mm) and the endplates were degenerated, targeted annular therapy would likely be of no clinical or functional benefit. Complete, Grade V annular fissures also were excluded, because then the injectate would likely flow out of the disk into the epidural space. This would allow little to no opportunity for the PRP graft to effect an intradiskal pro-healing change.
Interestingly, participants who elicited concordant pain at 2 levels and were treated with PRP for both disks showed superior improvements in all outcome measures at 1 year compared with those participants who elicited concordant pain at one level and subsequently received treatment for the single disk. There were no significant differences in mean outcome measure scores at baseline between these 2 subgroups.
The least amount of contrast necessary to elicit a pain response was injected in the IVD with the intention of leaving sufficient space in the disk to accommodate PRP volume. We did not use a pressure-controlled manometry system because in the authors’ experience, these systems require greater volume of contrast to elicit a pain response compared to manual administration. In most participants, a pain response was elicited with injection of less than 1 ml of contrast. In a small group of participants, 2 mL of contrast was required. In the authors’ experience, a disk that is not completely disrupted will typically only hold 3-4 mL of injectate. This limited the volume of PRP in most participants to between 1 and 2 mL. Furthermore, for each participant, treatment was limited to 1 injection at the time of diskography to minimize the possibility of adverse reaction from multiple disk punctures .
One limitation of the study was the limited follow-up time of only 8 weeks for the control group. Having a longer follow-up interval on the control participants (6 months, 1 year) would possibly enable detection of greater differences between groups over time. Although there were statistically significant differences between PRP and control groups over 8 weeks, these changes were not detected in all outcome measures, and the changes in NRS pain scores were modest at best. In retrospect, there were some participants in the study who had more disk degeneration and larger protrusions than others, which likely increased some of the variability in witnessed responses. Finally, there was no data collection on cell counts or biochemical analysis of the PRP and there was no routine radiologic follow-up to see if morphologic disk changes occurred with clinical improvement. Future studies should include these data to better learn about the effects of cell therapy on lumbar disk disease.
A priori power analysis had indicated that a sample size of 72 participants (48 treatment participants, 24 control participants) was necessary to achieve greater than 80% power to detect a 9-point change in FRI score with estimated standard deviations of plus or minus 15 in a 2-way repeated measures analysis of variance model with 5 time points. However, stopping rules were applied because of logistical concerns (ie, time and financial constraints) and an overwhelming number of control patients requesting to be unblinded from the study protocol and requesting the treatment specifically after the 8-week follow-up period (n = 15, 68.2%). As a result, the comparative analysis was modified from 5 time points to 4. Given the new parameters of the study, we were slightly underpowered to detect the demonstrated difference in FRI score at 8 weeks between the study groups. As an additional consequence, the variance-covariance matrix of the original power analysis was not used for actual analysis of collected data. However, given the sample sizes used for this study, we were adequately powered to detect a 10-point difference between groups with a four time point study design.