Autologous Conditioned Serum: Functional and Clinical Results

Knee Osteoarthritis Clinical Trial

Official title:

Autologous Conditioned Serum: Functional and Clinical Results Using a Novel Disease Modifying Agent for the Management of Knee Osteoarthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03850080
• Other study ID #: 1ACS
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 6, 2017
• Est. completion date: September 28, 2018

Study information

• Verified date: February 2019
• Source: Ospedale San Raffaele
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to investigate the potential ability of autologous conditioned serum (ACS) to decrease the pain and improve the joint functionality in patients affected by knee osteoarthritis (OA).

Description:

Fifteen patients with clinical and radiological signs of OA of the hip or knee were recruited for this study. Each patient received 4 injections of ACS (Orthokine®) at the site of OA once per week for 4 weeks. Clinical and functional evaluation were performed using VAS scale for pain, WOMAC scale and KSS functional and clinical scores before the first injection, at one week, at two weeks, at three weeks, at one month and at six months. Statistical analysis was done with the Wilcoxon Signed-Rank Test.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: September 28, 2018
• Est. primary completion date: September 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years and older

Eligibility

Inclusion Criteria:

• knee osteoarthritis >3 months in clinical and radiographic signs

• VAS for pain >50mm

Exclusion Criteria:

• Hepatitis B

• Hepatitis C

• HIV

• pregnancy

• drug abuse

• other intra-articular injections <6 months

• surgery on affected knee <12 months

Related Conditions & MeSH terms

• Cartilage Degeneration
• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Autologous Conditioned Serum
Fifteen patients with clinical and radiological signs of OA of the knee were recruited for this study. 50mL of whole blood were taken using a special syringe containing CrSO4-coated grade glass beads in order to promote IL-1ra synthesis and aggregation.The incubation period lasted 7 hours after which, the blood-filled syringes were centrifuged and the serum supernatant was filtered and aliquoted into four 3mL portions. The aliquots were stored at -20oC until their use was necessary. Patients received 1 intra-articular injection for 4 consecutive weeks at the site of OA.

Locations

Country	Name	City	State
Italy	Ospedale San Raffaele	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Ospedale San Raffaele

Country where clinical trial is conducted

Italy, 

References & Publications (15)

Alvarez-Camino JC, Vázquez-Delgado E, Gay-Escoda C. Use of autologous conditioned serum (Orthokine) for the treatment of the degenerative osteoarthritis of the temporomandibular joint. Review of the literature. Med Oral Patol Oral Cir Bucal. 2013 May 1;18(3):e433-8. Review. — View Citation

Auw Yang KG, Raijmakers NJ, van Arkel ER, Caron JJ, Rijk PC, Willems WJ, Zijl JA, Verbout AJ, Dhert WJ, Saris DB. Autologous interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective rando — View Citation

Baltzer AW, Moser C, Jansen SA, Krauspe R. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. Osteoarthritis Cartilage. 2009 Feb;17(2):152-60. doi: 10.1016/j.joca.2008.06.014. Epub 2008 Jul 31. — View Citation

Bhandari M, Bannuru RR, Babins EM, Martel-Pelletier J, Khan M, Raynauld JP, Frankovich R, Mcleod D, Devji T, Phillips M, Schemitsch EH, Pelletier JP. Intra-articular hyaluronic acid in the treatment of knee osteoarthritis: a Canadian evidence-based perspective. Ther Adv Musculoskelet Dis. 2017 Sep;9(9):231-246. doi: 10.1177/1759720X17729641. Epub 2017 Sep 12. Review. Erratum in: Ther Adv Musculoskelet Dis. 2017 Nov;9(11):295. — View Citation

Buckland-Wright C. Subchondral bone changes in hand and knee osteoarthritis detected by radiography. Osteoarthritis Cartilage. 2004;12 Suppl A:S10-9. Review. — View Citation

Calich AL, Domiciano DS, Fuller R. Osteoarthritis: can anti-cytokine therapy play a role in treatment? Clin Rheumatol. 2010 May;29(5):451-5. doi: 10.1007/s10067-009-1352-3. Epub 2010 Jan 27. Review. — View Citation

Fox BA, Stephens MM. Treatment of knee osteoarthritis with Orthokine-derived autologous conditioned serum. Expert Rev Clin Immunol. 2010 May;6(3):335-45. doi: 10.1586/eci.10.17. — View Citation

Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011 Jan;7(1):33-42. doi: 10.1038/nrrheum.2010.196. Epub 2010 Nov 30. Review. — View Citation

Klocke R, Levasseur K, Kitas GD, Smith JP, Hirsch G. Cartilage turnover and intra-articular corticosteroid injections in knee osteoarthritis. Rheumatol Int. 2018 Mar;38(3):455-459. doi: 10.1007/s00296-018-3988-2. Epub 2018 Feb 2. — View Citation

Martel-Pelletier J, Alaaeddine N, Pelletier JP. Cytokines and their role in the pathophysiology of osteoarthritis. Front Biosci. 1999 Oct 15;4:D694-703. Review. — View Citation

Nixon AJ, Grol MW, Lang HM, Ruan MZC, Stone A, Begum L, Chen Y, Dawson B, Gannon F, Plutizki S, Lee BHL, Guse K. Disease-Modifying Osteoarthritis Treatment With Interleukin-1 Receptor Antagonist Gene Therapy in Small and Large Animal Models. Arthritis Rheumatol. 2018 Nov;70(11):1757-1768. doi: 10.1002/art.40668. Epub 2018 Sep 10. — View Citation

Nuki G. Osteoarthritis: a problem of joint failure. Z Rheumatol. 1999 Jun;58(3):142-7. Review. — View Citation

Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001 Jun;44(6):1237-47. Review. — View Citation

Shewale AR, Barnes CL, Fischbach LA, Ounpraseuth ST, Painter JT, Martin BC. Comparative Effectiveness of Intra-Articular Hyaluronic Acid and Corticosteroid Injections on the Time to Surgical Knee Procedures. J Arthroplasty. 2017 Dec;32(12):3591-3597.e24. doi: 10.1016/j.arth.2017.07.007. Epub 2017 Jul 14. — View Citation

Wehling P, Moser C, Frisbie D, McIlwraith CW, Kawcak CE, Krauspe R, Reinecke JA. Autologous conditioned serum in the treatment of orthopedic diseases: the orthokine therapy. BioDrugs. 2007;21(5):323-32. Review. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC)	24 questions each scaled out of 100mm. 5 questions regarding pain. 2 questions regarding rigidity. 17 questions regarding difficulty in various activities. Total score out of 240 expressed as a percentage. Minimum score 0. Max score 100. Greater score implies worsening symptomatology.	6 months
Primary	Knee Society Score (KSS)	Clinical Score. Pain is measured out of 50 (no pain = 50, severe pain = 0). Range of motion (1 point for every 5 degress of flexion. Max points = 25). Stability; anteroposterior (<5 degrees 10, 5-10 degrees 5, >10 degrees 0); mediolateral (<5 degrees = 10, 5-10 degrees = 5, >10 degrees = 0); Flexion contracture (5-10 degrees = -2, 10-15 degrees = -5, 16-20 degrees = -10, >20 degrees = -15); Extension lag (<10 degrees = -5, 10-20 degrees = -10, 20 degrees = -15); Alignment (0-4 degrees = 0, 5-15 degrees = 3 points for each degree).; Functional Score. Consists of walking score based on how many blocks (100m) patient can walk without stopping (unlimited = 100, >10 blocks = 40, 5-10 blocks = 30, <5 blocks = 20, housebound = 10, unable = 0); Stairs (normal = 50, normal up down with support = 40, up and down with support = 30, up with support down unable = 15, unable = 0); Functional deductions (cane = -5, two canes = -10, crutches or walker = -20)	6 months
Primary	Visual Analog Score for Pain	Subjective evaluation of pain reported by each patient on average since the last visit. Minimum = 0. Maximum = 10	6 months