Clinical trial NCT04816747: Intradiscal and Intra-articular Injection of Autologous Platelet-Rich-Plasma (PRP) in Patients With Lumbar Degenerative Disc Disease and Facet Joint Syndrome
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Degenerative Disc Disease
Facet Joint Syndrome
Keywords: Platelet-rich-plasma
intradiscal
intra-articular
degenerative disc disease
facet joint syndrome
facet joint arthritis
Lead sponsor: European Interbalkan Medical Center
Sponsor class: OTHER
Collaborators: name: Aristotle University Of Thessaloniki
First posted: 2021-03-25
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants fulfilling the predetermined inclusion criteria will be considered eligible to be subjected to treatment with PRP. Injection of PRP will be conducted intradiscally and/or intra-articularly, in cases of lumbar DDD and/or FJS, as defined by clinical and radiologic assessment. Hence, all participants will be assigned to the same intervention.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Β. 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.

Primary outcomes:
measure: Change in Pain Visual Analogue Scale (VAS) Scores from baseline to post intervention during follow-up
timeFrame: VAS score is planned to be evaluated preoperatively, immediately after intervention, at 6 weeks and at 3,6,12 and 24 months postoperatively.
measure: Alteration in Short-Form 36 (SF-36) Medical Health Survey Questionnaire Scores from baseline to post intervention during follow-up
timeFrame: 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 outcomes:
measure: Complications
timeFrame: Complications will be constantly recorded during the study immediately after intervention, at 6 weeks and at 3,6,12 and 24 months postoperatively.
Other outcomes:
Locations:
Study officials:
affiliation: Spine Department and Deformities, Interbalkan European Medical Center, Thessaloniki, PC 55535, Greece; Department of Minimally Invasive and Endoscopic Spine Surgery, Athens Medical Center, Athens, PC 15124, Greece
name: Stylianos Kapetanakis, Assistant Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Spine Department and Deformities, Interbalkan European Medical Center, Thessaloniki, PC 55535, Greece
name: Nikolaos Gkantsinikoudis, PhD Candidate
role: STUDY_CHAIR
affiliation: Department of Physiology and Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th), Thessaloniki, PC 54124, Greece
name: Aristeidis Kritis, Associate Professor
role: STUDY_CHAIR
References:
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.
citation: 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.
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.
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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. doi: 10.4103/0974-8237.193260.
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