Clinical trial NCT02370420: Intra-Articular Injections of Platelet-Rich Plasma in Knee Osteoarthritis: Unique Application Versus Triple Application
Official title: Intra-Articular Injections of Platelet-Rich Plasma in Knee Osteoarthritis: Unique Application Versus Triple Application
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthritis
Keywords: Platelet-rich plasma
Osteoarthritis
Lead sponsor: Universidad Autonoma de Nuevo Leon
Sponsor class: OTHER
First posted: 2015-02-25
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators include patients attending the outpatient clinic in the area of Orthopedics and Traumatology of the investigators hospital with a diagnosis of knee osteoarthritis, which treatment is medical. Patients will be divided into two groups. In both groups, they will be given verbal, clear and detailed information on the approach to follow, the intra-articular application of Platelet-Rich Plasma in the knee, plus rehabilitation exercises. In the first group will be held single application, while in the second group three applications will be made at an interval of two weeks each. Both groups will be assessed before and after application, together with outpatient follow-up by the SF-12 Health Survey (SF-12), Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analogue Scale (VAS).

Detailed description: Osteoarthritis (OA ) refers to a clinical syndrome of joint pain with a multifactorial etiology , with the gradual loss of articular cartilage, osteophytosis formation, subchondral bone remodeling and inflammation of the joint. Is the most common cause of knee pain, and one of the leading causes of disability and dependence of the adult population that generates large expenditures in the area of health.

The clinical diagnosis of OA is primarily clinical - radiological, based on a complete medical history and physical examination directed. No laboratory studies are routinely requested since there is no specific diagnostic test or pathognomonic for diagnosis. Physical examination is most important.

The ideal treatment is a multidisciplinary one, and must meet the objectives of achieving anesthesia, reduce disability and improve joint function and patient's quality life, with low toxicity of drugs. Several conservative treatments are recommended by clinical guidelines. Some nonpharmacologic measures are: patient education, exercise, weight loss, modification of footwear, using the local cryotherapy, acupuncture and electromagnetic therapy. Drug therapy can be summarized in paracetamol, NSAIDs, opioids, and slow-acting drugs. If these oral drugs do not work can be administered intra-articularly (corticosteroids, viscosupplementation products, and blood derivates).

Platelet-Rich Plasma (PRP) is a rich source of growth factors such as Platelet-derived growth factor (PDGF), transforming growth factor β (TGF- β ), vascular endothelial growth factor (VEGF), like growth factor type I insulin (IGF- I), vascular endothelial growth factor (EGF), among others. For these growth factors are released, the platelets need to be activated by substances such as calcium chloride, calcium gluconate or thrombin. Once activated , growth factors are secreted, reaching a peak concentration 10 minutes. It is known that GF, PDGF and TGF -B stimulate chondrogenesis helping solving clinical manifestations of patients studied.

The investigators include patients attending the outpatient clinic in the area of Orthopedics and Traumatology of our hospital with a diagnosis of knee osteoarthritis, which treatment is medical. Patients will be divided into two groups. In both groups, they will be given verbal, clear and detailed information on the approach to follow, the intra-articular application of Platelet-Rich Plasma in the knee, plus rehabilitation exercises. In the first group will be held single application, while in the second group three applications will be made at an interval of two weeks each. Both groups will be assessed before and after application, together with outpatient follow-up by the SF-12, WOMAC and Visual Analogue Scale.

The PRP would be obtained through previous an asepsis and antisepsis of the patient's arm, 30cc of blood form the Basilic vein would be extracted.

Each sample will initially centrifuged at 1800 rpm for 10 minutes in a centrifuge and the sample would be separated into three layers : 1- Red Cell (lower) White 2- (plasma rich in growth factors) Yellow 3- ( plasma poor in growth factors ).1000 ul PRP ( yellow layer ) is extracted by placing it in 15 mL Falcon tubes for subsequently performing a second step of centrifugation at 3400 rpm for 12 minutes. The top layer of platelet poor plasma is removed and stayed with the lower layer, the PRP (3-5 mL ) . Before application in the patient's knee,calcium gluconate 10% was added, 0.15 mL per milliliter of PRP obtained. The sample then would be aspirated with a 10 mL syringe for the application to the patient.

After asepsis and antisepsis of where the puncture site , sterile drapes were placed clearing the workspace, the PRP is injected with a technique 45 ° at the corner superior- lateral patellar, reaching the joint capsule. Once injected the PRP, a sterile pad on the application area will be placed.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 90 years
* Patients with no previous treatment
* Patients with Knee osteoarthritis grade 1-2 ( Kellgren-Lawrence based on radiographic findings)

Exclusion Criteria:

* Age \<18 and \> 90 years
* Patients with Knee osteoarthritis grade 3-4 ( Kellgren-Lawrence based on radiographic findings)
* Patients with asociated Rheumatic syndromes
* Patients with anticoagulant therapy
* Patients with hepatic problems, Diabetes Mellitus, Coagulopathy, hearth conditions, immunodepressed, or infections
* Pregnant patients
* Patients with prosthetic or orthotic.
* Patients with hemoglobin values \< 11g/dl , platelets \< 150,000/μL

Primary outcomes:
measure: Change in the Western Ontario and McMaster Universities (WOMAC) Ostearthritis Index (Therapeutic Effect)
timeFrame: Baseline,3 weeks, 6 weeks, 12 weeks, 24 weeks
Secondary outcomes:
measure: Change in the SF-12 Health Survey (Quality of Life)
timeFrame: Baseline,3 weeks, 6 weeks, 12 weeks, 24 weeks
measure: Change in the Visual Analog Scale (VAS) (Global Pain)
timeFrame: Baseline,3 weeks, 6 weeks, 12 weeks, 24 weeks
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Facultad de Medicina UANL
state: Nuevo Leon
Study officials:
affiliation: Universidad Autonoma de Nuevo Leon
name: Felix Vilchez, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Martel-Pelletier J, Boileau C, Pelletier JP, Roughley PJ. Cartilage in normal and osteoarthritis conditions. Best Pract Res Clin Rheumatol. 2008 Apr;22(2):351-84. doi: 10.1016/j.berh.2008.02.001.
citation: Jevsevar DS, Brown GA, Jones DL, Matzkin EG, Manner PA, Mooar P, Schousboe JT, Stovitz S, Sanders JO, Bozic KJ, Goldberg MJ, Martin WR 3rd, Cummins DS, Donnelly P, Woznica A, Gross L; American Academy of Orthopaedic Surgeons. The American Academy of Orthopaedic Surgeons evidence-based guideline on: treatment of osteoarthritis of the knee, 2nd edition. J Bone Joint Surg Am. 2013 Oct 16;95(20):1885-6. doi: 10.2106/00004623-201310160-00010. No abstract available.
citation: Wang-Saegusa A, Cugat R, Ares O, Seijas R, Cusco X, Garcia-Balletbo M. Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life. Arch Orthop Trauma Surg. 2011 Mar;131(3):311-7. doi: 10.1007/s00402-010-1167-3. Epub 2010 Aug 17.
citation: Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ. 2003;81(9):646-56. Epub 2003 Nov 14.
citation: Park SI, Lee HR, Kim S, Ahn MW, Do SH. Time-sequential modulation in expression of growth factors from platelet-rich plasma (PRP) on the chondrocyte cultures. Mol Cell Biochem. 2012 Feb;361(1-2):9-17. doi: 10.1007/s11010-011-1081-1. Epub 2011 Sep 29.
citation: Kon E, Buda R, Filardo G, Di Martino A, Timoncini A, Cenacchi A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc. 2010 Apr;18(4):472-9. doi: 10.1007/s00167-009-0940-8. Epub 2009 Oct 17.