Intradiscal and Intra-articular Injection of Autologous Platelet-Rich-Plasma (PRP) in Patients With Lumbar Degenerative Disc Disease and Facet Joint Syndrome

Degenerative Disc Disease Clinical Trial

Official title:

Intradiscal and Intra-articular Injection of Autologous Platelet-Rich-Plasma (PRP) in Patients With Lumbar Degenerative Disc Disease and Facet Joint Syndrome: A Prospective, Single-arm, Open Label Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04816747
• Other study ID #: Not administered
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 2022
• Est. completion date: October 2024

Study information

• Verified date: March 2022
• Source: European Interbalkan Medical Center
• Contact: Stylianos Kapetanakis, Assistant Professor
• Phone: +306972707384
• Email: stkapetanakis[@]yahoo.gr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Autologous Platelet-Rich-Plasma (PRP) represents a regenerative therapy that has gained remarkable ground in the field of orthopaedics in recent years. PRP has been implemented for a plethora of musculoskeletal ailments, being associated with minor complications and noteworthy efficacy (Akeda et al., 2019). PRP has been depicted to contain a variety of growth factors crucial for regulation of cell proliferation and migration as well as extracellular matrix synthesis (Cheng et al., 2019). Furthermore, therapeutic effect of PRP administration is considered to be additionally exerted via its anti-inflammatory and immunoregulative properties, as it has been delineated to induce regional decrease of pro-inflammatory mediators at the injection site (Hirase et al., 2020).

Lumbar Degenerative Disc Disease (DDD) and Facet Joint Syndrome (FJS) constitute chronic degenerative conditions of lumbar spine that have been associated with substantial morbidity and disability in recent years. Besides the noted progress in comprehension of these conditions' pathogenesis, available therapeutic modalities remain extremely limited and controversial, being not capable of altering the natural progress of underlying disease (Wu et al., 2016; Wu et al., 2017; Hirase et al., 2020).

Autologous PRR has been recommended as a beneficial alternative instead of conventional treatment strategies for interventional management of lumbar DDD and FJS (Aufiero et al., 2015; Navani and Hames, 2015; Kirchner and Anitua, 2016; Levi et al., 2016; Tuakli-Wosornu et al., 2016; Wu et al., 2016; Akeda et al., 2017; Lutz GE, 2017; Wu et al., 2017; Cheng et al., 2019). Results of these studies indicated that intra-discal and intra-articular injection of PRP for DDD and FJS respectively is characterized by safety and satisfactory efficacy in reducing intensity of clinical manifestations, exerting also potentially regenerative effects. However, quality of available evidence is remarkably low, since in the overwhelming majority of these studies was a limited number of patients evaluated. Furthermore, determined follow-up intervals were not extended and, most importantly, patients were not majorly with rigorous clinical and radiologic criteria selected.

Aim of this study is to investigate the precise effects of intradiscal and intra-articular injection of PRP in patients with early-stage lumbar DDD and FJS, as determined by particular radiologic classifications. The prospective design, the defined greater number of recruited individuals in pilot analysis as well as the comparatively greater follow-up underline the originality of our protocol.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Eligibility criteria will be distinctly applied in participants with lumbar DDD and FJS prior to treatment application.

A. Participants with lumbar DDD

Inclusion Criteria

• Recurring low back pain persistent for more than 6 months demonstrating discogenic origin (i.e. localized at midline, exacerbated in seated position and alleviated in bed rest)

• Failure of initially implemented conservative measures (medication regimen and/or physical therapy sessions or other injections)

• Imaginary findings of Grade I-III DDD according to radiologic MRI-based classification proposed by Pfirrmann et al. (Pfirrmann et al., 2001)

• Absence of exclusion criteria, as defined below.

Exclusion Criteria

• Presence of local or systemic infection signs (clinical and laboratory)

• Concurrent known systemic inflammatory disease with musculoskeletal manifestations or other chronic inflammatory disease

• Concurrent known hemorrhagic disorder or antithrombotic regimen

• Presence of Grade IV-V DDD according to Pfirrmann classification (Pfirrmann et al., 2001)

• Spondylolysis/Spondylolisthesis

• Intervertebral Disc Herniation

• Previous spinal surgery

• Spinal Stenosis

• Primary or Secondary spinal tumour

• Spinal fracture in past 6 months

• Diagnosed psychiatric disorder

• Epidural steroid or other intradiscal injection or within past 30 days

• Administration of NSAIDs, steroids or dietary supplements with anti-inflammatory properties within past 30 days.

?. Participants with lumbar FJS

Inclusion Criteria

• Recurring low back pain persistent for more than 6 months with no radiation to buttock or lower limb, presence of exacerbation in lateral bending, rotation and extension and paraspinal localization featuring reproduction with pressure.

• Failure of conservative treatment measures (medication regimen and/or physical therapy sessions or other injections).

• Radiologic findings of Grade I-II FJS according to CT-based classification proposed by Suri et al. (Suri et al., 2010)

• Absence of exclusion criteria, as designated below.

Exclusion Criteria

• Clinical manifestations of radiculopathy

• Presence of local or systemic infection signs (clinical and laboratory)

• Concurrent known systemic inflammatory disease with musculoskeletal manifestations or other chronic inflammatory disease

• Concurrent known hemorrhagic disorder or antithrombotic regimen.

• Presence of Grade III-IV FJS according to proposed classification of Suri et al. (Suri et al., 2010)

• Spondylolysis/Spondylolisthesis

• Intervertebral Disc Herniation

• Previous spinal surgery

• Spinal Stenosis

• Primary or Secondary spinal tumour

• Spinal fracture in past 6 months

• Diagnosed psychiatric disorder

• Previous intra-articular steroid injection within past 30 days

• Administration of NSAIDs, steroids or dietary supplements with anti-inflammatory properties within past 30 days.

Related Conditions & MeSH terms

• Degenerative Disc Disease
• Facet Joint Syndrome
• Intervertebral Disc Degeneration
• Spinal Diseases
• Syndrome

Intervention

Biological:
• Autologous PRP
Participants enrolled in this study will be managed with intradiscal and/or intra-articular injections of autologous PRP according to features of underlying pathology. Participants featuring FJS will be prior to PRP diagnostically and therapeutically injected with local anesthetic in order to verify FJS as the etiology of experienced pain. Injected PRP solution volume is designed to be 0.5-1 ml and 0.5 ml in cases of intradiscal and intra-articular injection, respectively. All participants are planned to receive a single dose of PRP, whilst a maximum of two compromised discs and four facet joints will be treated in each patient.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Stylianos Kapetanakis	School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th.), Greece

References & Publications (14)

Akeda K, Ohishi K, Masuda K, Bae WC, Takegami N, Yamada J, Nakamura T, Sakakibara T, Kasai Y, Sudo A. Intradiscal Injection of Autologous Platelet-Rich Plasma Releasate to Treat Discogenic Low Back Pain: A Preliminary Clinical Trial. Asian Spine J. 2017 Jun;11(3):380-389. doi: 10.4184/asj.2017.11.3.380. Epub 2017 Jun 15. — View Citation

Akeda K, Yamada J, Linn ET, Sudo A, Masuda K. Platelet-rich plasma in the management of chronic low back pain: a critical review. J Pain Res. 2019 Feb 25;12:753-767. doi: 10.2147/JPR.S153085. eCollection 2019. Review. — View Citation

Aufiero D, Vincent H, Sampson S, Bodor M. Regenerative Injection Treatment in the Spine: Review and Case Series with Platelet Rich Plasma. J Stem Cells Res, Rev & Rep. 2015;2(1):1019.

Cheng J, Santiago KA, Nguyen JT, Solomon JL, Lutz GE. Treatment of symptomatic degenerative intervertebral discs with autologous platelet-rich plasma: follow-up at 5-9 years. Regen Med. 2019 Sep;14(9):831-840. doi: 10.2217/rme-2019-0040. Epub 2019 Aug 29. — View Citation

Hirase T, Jack Ii RA, Sochacki KR, Harris JD, Weiner BK. Systemic Review: Is an Intradiscal Injection of Platelet-Rich Plasma for Lumbar Disc Degeneration Effective? Cureus. 2020 Jun 25;12(6):e8831. doi: 10.7759/cureus.8831. Review. — View Citation

Kirchner F, Anitua E. Intradiscal and intra-articular facet infiltrations with plasma rich in growth factors reduce pain in patients with chronic low back pain. J Craniovertebr Junction Spine. 2016 Oct-Dec;7(4):250-256. — View Citation

Levi D, Horn S, Tyszko S, Levin J, Hecht-Leavitt C, Walko E. Intradiscal Platelet-Rich Plasma Injection for Chronic Discogenic Low Back Pain: Preliminary Results from a Prospective Trial. Pain Med. 2016 Jun;17(6):1010-22. doi: 10.1093/pm/pnv053. Epub 2015 Dec 26. — View Citation

Lutz GE. Increased Nuclear T2 Signal Intensity and Improved Function and Pain in a Patient One Year After an Intradiscal Platelet-Rich Plasma Injection. Pain Med. 2017 Jun 1;18(6):1197-1199. doi: 10.1093/pm/pnw299. — View Citation

Navani A, Hames A. Platelet-rich plasma injections for lumbar discogenic pain: A preliminary assessment of structural and functional changes. Techniques in Regional Anesthesia and Pain Management 2015;19(1-2):38-44.

Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976). 2001 Sep 1;26(17):1873-8. — View Citation

Suri P, Katz JN, Rainville J, Kalichman L, Guermazi A, Hunter DJ. Vascular disease is associated with facet joint osteoarthritis. Osteoarthritis Cartilage. 2010 Sep;18(9):1127-32. doi: 10.1016/j.joca.2010.06.012. Epub 2010 Jul 13. — View Citation

Tuakli-Wosornu YA, Terry A, Boachie-Adjei K, Harrison JR, Gribbin CK, LaSalle EE, Nguyen JT, Solomon JL, Lutz GE. Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study. PM R. 2016 Jan;8(1):1-10; quiz 10. doi: 10.1016/j.pmrj.2015.08.010. Epub 2015 Aug 24. — View Citation

Wu J, Du Z, Lv Y, Zhang J, Xiong W, Wang R, Liu R, Zhang G, Liu Q. A New Technique for the Treatment of Lumbar Facet Joint Syndrome Using Intra-articular Injection with Autologous Platelet Rich Plasma. Pain Physician. 2016 Nov-Dec;19(8):617-625. — View Citation

Wu J, Zhou J, Liu C, Zhang J, Xiong W, Lv Y, Liu R, Wang R, Du Z, Zhang G, Liu Q. A Prospective Study Comparing Platelet-Rich Plasma and Local Anesthetic (LA)/Corticosteroid in Intra-Articular Injection for the Treatment of Lumbar Facet Joint Syndrome. Pain Pract. 2017 Sep;17(7):914-924. doi: 10.1111/papr.12544. Epub 2017 Feb 22. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Pain Visual Analogue Scale (VAS) Scores from baseline to post intervention during follow-up	Participants will be asked to indicate the pain level according to their subjective perception with as spot in a unipolar horizontal line of 100 mm (0: no pain, 100: the worst pain possible). Scores will be calculated in mm, and an one-decimal place approach will be adopted for record.	VAS score is planned to be evaluated preoperatively, immediately after intervention, at 6 weeks and at 3,6,12 and 24 months postoperatively.
Primary	Alteration in Short-Form 36 (SF-36) Medical Health Survey Questionnaire Scores from baseline to post intervention during follow-up	Participants will be asked to complete the analogous questionnaire, so that eight distinct parameters reflecting general health status are evaluated: physical function (PF), role-physical (RP), bodily pain (BP), general health (GH), energy, fatigue and vitality (V), social function (SF), role-emotional (RE) and mental health (MH). Computational processing of collected data will be subsequently conducted, so that each parameter is expressed by a percentage. Greater scores in these 8 parameters are associated with ameliorated Health-Related Quality of Life (HRQoL).	SF-36 questionnaire is planned to be evaluated preoperatively, immediately after intervention, at 6 weeks and at 3,6,12 and 24 months postoperatively.
Secondary	Complications	Safety of implemented procedure is designed to be determined via the record of frequency and kind of perioperative associated complications.	Complications will be constantly recorded during the study immediately after intervention, at 6 weeks and at 3,6,12 and 24 months postoperatively.