Efficacy of Subcutaneous Injection of Etanercept for Moderate and Severe Knee Osteoarthritis

NCT02722811 | Unknown DMC

• 1 other identifier: SI-ETN-KOA-201614
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Primary aim: evaluate efficacy of subcutaneous injection of etanercept for moderate and severe knee osteoarthritis. Second aim: investigate the potentiality of serum cytokines (TNF-α, Interleukin 1-α (IL1-α), IL1-β, matrix metalloproteinases1 (MMP1), MMP13) to predict the response of subcutaneous injection of etanercept for moderate and severe knee osteoarthritis.

Conditions

Osteoarthritis Of Knee

Keywords

Etanercept; Osteoarthritis Of Knee; TNF-α; IL-1α; Subcutaneous Injection

Outcome Measures

Primary Outcomes (2)

• Pain VAS score(Pain Visual Analogue Scale/Score)

  Changes from the baseline to 8 weeks and 12 weeks to evaluate the treatment efficacy

  baseline to 8 weeks and 12 weeks

• KOOS score(The Knee injury and Osteoarthritis Score)

  Changes from the baseline to 8 weeks and 12 weeks to evaluate the treatment efficacy

  baseline to 8 weeks and 12 weeks

Secondary Outcomes (10)

• 30s-CST score(30 seconds Sit/chair Test)

  baseline to 8 weeks and 12 weeks

• 40m FPWT score(40 meters fast walking test)

  baseline to 8 weeks and 12 weeks

• Assessment score under ultrasound

  baseline to 8 weeks and 12 weeks

• Assessment score under MRI

  baseline to 8 weeks and 12 weeks

• TNF-α (pg/ml) level in serum

  baseline to 8 weeks and 12 weeks

Other Outcomes (1)

• Adverse event

  2 weeks, 4 weeks, 8 weeks and 12 weeks

Study Arms (2)

Etanercept treatment group

EXPERIMENTAL

Subcutaneous injection etanercept of 50 mg/w and Health education, exercise and diet guidance; treatment: 8 weeks

Drug: Etanercept; Other: Health education, exercise and diet guidance

Routine care group

PLACEBO COMPARATOR

Health education, exercise and diet guidance; treatment: 8 weeks

Other: Health education, exercise and diet guidance

Interventions

Etanercept DRUG

etanercept of 50 mg/w, subcutaneous injection; treatment: 8 weeks

Etanercept treatment group

Health education, exercise and diet guidance OTHER

Health education, exercise and diet guidance in patient; treatment: 8 weeks

Etanercept treatment group; Routine care group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give full consent;
• According with classification of "Clinical Image" of 1986 American college of rheumatology criteria in osteoarthritis of the knee ;
• Grade II-IV of Kellgren-Lawrence (KL) grading system, revealing synovial inflammation or synovial fluid by combining ultrasound and MRI
• Knee pain for at least 1 Month and average pain of last week rated as moderate and severe, Pain VAS Score\>4;
• Fertile women agreed to adopt effective contraceptive measures during the test.

You may not qualify if:

• Allergic to pharmaceutical ingredients;
• Received Tumor Necrosis Factor inhibitor (TNFI) or other biologics preparation within 3 months;
• Received physical therapy or articular injection, taking antidepressants or antispasmodic, opioids within 3 months ;
• Patients with history of knee surgery or upcoming surgery within 10 years;
• Patients accompanied by other complications or joint disease (such as septic arthritis, osteonecrosis,haemochromatosis, ochronosis, etc.);
• Patients with active or a history of recurrent infections;
• Patients existing active tuberculosis (TB) or has a history of active TB;
• Patients with positive on hepatitis b surface antigen or hepatitis c antibody;
• Patients with a history of severe lung disease, tumor;
• Patients with severely abnormal function on liver and kidney (liver enzyme \> = 2 times normal, creatinine \> = normal);
• Patients with pregnancy, ready for pregnancy or lactation;
• Patients with other conditions which not suitable for use of Etanercept.

Sponsors & Collaborators

• First Affiliated Hospital of Harbin Medical University: lead
• Shanghai Baiying Medical Technology Co., Ltd.: collaborator

Study Sites (1)

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

RECRUITING

Related Publications (26)

• Ge Z, Hu Y, Heng BC, Yang Z, Ouyang H, Lee EH, Cao T. Osteoarthritis and therapy. Arthritis Rheum. 2006 Jun 15;55(3):493-500. doi: 10.1002/art.21994. No abstract available.

  PMID: 16739189 BACKGROUND

• Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012 Jun;64(6):1697-707. doi: 10.1002/art.34453. Epub 2012 Mar 5. No abstract available.

  PMID: 22392533 BACKGROUND

• Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008 Jan;58(1):26-35. doi: 10.1002/art.23176.

  PMID: 18163497 BACKGROUND

• Dillon CF, Rasch EK, Gu Q, Hirsch R. Prevalence of knee osteoarthritis in the United States: arthritis data from the Third National Health and Nutrition Examination Survey 1991-94. J Rheumatol. 2006 Nov;33(11):2271-9. Epub 2006 Oct 1.

  PMID: 17013996 BACKGROUND

• Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF. The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum. 1987 Aug;30(8):914-8. doi: 10.1002/art.1780300811.

  PMID: 3632732 BACKGROUND

• Jordan JM, Helmick CG, Renner JB, Luta G, Dragomir AD, Woodard J, Fang F, Schwartz TA, Abbate LM, Callahan LF, Kalsbeek WD, Hochberg MC. Prevalence of knee symptoms and radiographic and symptomatic knee osteoarthritis in African Americans and Caucasians: the Johnston County Osteoarthritis Project. J Rheumatol. 2007 Jan;34(1):172-80.

  PMID: 17216685 BACKGROUND

• Dahaghin S, Bierma-Zeinstra SM, Ginai AZ, Pols HA, Hazes JM, Koes BW. Prevalence and pattern of radiographic hand osteoarthritis and association with pain and disability (the Rotterdam study). Ann Rheum Dis. 2005 May;64(5):682-7. doi: 10.1136/ard.2004.023564. Epub 2004 Sep 16.

  PMID: 15374852 BACKGROUND

• McCarberg B, Tenzer P. Complexities in the pharmacologic management of osteoarthritis pain. Curr Med Res Opin. 2013 May;29(5):539-48. doi: 10.1185/03007995.2013.785391. Epub 2013 Apr 3.

  PMID: 23489409 BACKGROUND

• Kotlarz H, Gunnarsson CL, Fang H, Rizzo JA. Insurer and out-of-pocket costs of osteoarthritis in the US: evidence from national survey data. Arthritis Rheum. 2009 Dec;60(12):3546-53. doi: 10.1002/art.24984.

  PMID: 19950287 BACKGROUND

• Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039-49. doi: 10.1002/art.1780290816.

  PMID: 3741515 BACKGROUND

• Chang A, Hochberg M, Song J, Dunlop D, Chmiel JS, Nevitt M, Hayes K, Eaton C, Bathon J, Jackson R, Kwoh CK, Sharma L. Frequency of varus and valgus thrust and factors associated with thrust presence in persons with or at higher risk of developing knee osteoarthritis. Arthritis Rheum. 2010 May;62(5):1403-11. doi: 10.1002/art.27377.

  PMID: 20213800 BACKGROUND

• Segal NA, Glass NA, Torner J, Yang M, Felson DT, Sharma L, Nevitt M, Lewis CE. Quadriceps weakness predicts risk for knee joint space narrowing in women in the MOST cohort. Osteoarthritis Cartilage. 2010 Jun;18(6):769-75. doi: 10.1016/j.joca.2010.02.002. Epub 2010 Feb 11.

  PMID: 20188686 BACKGROUND

• Baker KR, Xu L, Zhang Y, Nevitt M, Niu J, Aliabadi P, Yu W, Felson D. Quadriceps weakness and its relationship to tibiofemoral and patellofemoral knee osteoarthritis in Chinese: the Beijing osteoarthritis study. Arthritis Rheum. 2004 Jun;50(6):1815-21. doi: 10.1002/art.20261.

  PMID: 15188358 BACKGROUND

• Slemenda C, Brandt KD, Heilman DK, Mazzuca S, Braunstein EM, Katz BP, Wolinsky FD. Quadriceps weakness and osteoarthritis of the knee. Ann Intern Med. 1997 Jul 15;127(2):97-104. doi: 10.7326/0003-4819-127-2-199707150-00001.

  PMID: 9230035 BACKGROUND

• Ikeda S, Tsumura H, Torisu T. Age-related quadriceps-dominant muscle atrophy and incident radiographic knee osteoarthritis. J Orthop Sci. 2005;10(2):121-6. doi: 10.1007/s00776-004-0876-2.

  PMID: 15815857 BACKGROUND

• Messier SP, Loeser RF, Mitchell MN, Valle G, Morgan TP, Rejeski WJ, Ettinger WH. Exercise and weight loss in obese older adults with knee osteoarthritis: a preliminary study. J Am Geriatr Soc. 2000 Sep;48(9):1062-72. doi: 10.1111/j.1532-5415.2000.tb04781.x.

  PMID: 10983905 BACKGROUND

• Topp R, Woolley S, Hornyak J 3rd, Khuder S, Kahaleh B. The effect of dynamic versus isometric resistance training on pain and functioning among adults with osteoarthritis of the knee. Arch Phys Med Rehabil. 2002 Sep;83(9):1187-95. doi: 10.1053/apmr.2002.33988.

  PMID: 12235596 BACKGROUND

• McCarthy GM, McCarty DJ. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J Rheumatol. 1992 Apr;19(4):604-7.

  PMID: 1375648 BACKGROUND

• Dreiser RL, Tisne-Camus M. DHEP plasters as a topical treatment of knee osteoarthritis--a double-blind placebo-controlled study. Drugs Exp Clin Res. 1993;19(3):117-23.

  PMID: 8112200 BACKGROUND

• Bradley JD, Brandt KD, Katz BP, Kalasinski LA, Ryan SI. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med. 1991 Jul 11;325(2):87-91. doi: 10.1056/NEJM199107113250203.

  PMID: 2052056 BACKGROUND

• Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M; Adenoma Prevention with Celecoxib (APC) Study Investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005 Mar 17;352(11):1071-80. doi: 10.1056/NEJMoa050405. Epub 2005 Feb 15.

  PMID: 15713944 BACKGROUND

• Petrella RJ, DiSilvestro MD, Hildebrand C. Effects of hyaluronate sodium on pain and physical functioning in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial. Arch Intern Med. 2002 Feb 11;162(3):292-8. doi: 10.1001/archinte.162.3.292.

  PMID: 11822921 BACKGROUND

• Goldring MB. The role of the chondrocyte in osteoarthritis. Arthritis Rheum. 2000 Sep;43(9):1916-26. doi: 10.1002/1529-0131(200009)43:93.0.CO;2-I. No abstract available.

  PMID: 11014341 BACKGROUND

• Hunter DJ, Felson DT. Osteoarthritis. BMJ. 2006 Mar 18;332(7542):639-42. doi: 10.1136/bmj.332.7542.639. No abstract available.

  PMID: 16543327 BACKGROUND

• Rai MF, Rachakonda PS, Manning K, Vorwerk B, Brunnberg L, Kohn B, Schmidt MF. Quantification of cytokines and inflammatory mediators in a three-dimensional model of inflammatory arthritis. Cytokine. 2008 Apr;42(1):8-17. doi: 10.1016/j.cyto.2008.02.004. Epub 2008 Mar 17.

  PMID: 18343681 BACKGROUND

• Towle CA, Hung HH, Bonassar LJ, Treadwell BV, Mangham DC. Detection of interleukin-1 in the cartilage of patients with osteoarthritis: a possible autocrine/paracrine role in pathogenesis. Osteoarthritis Cartilage. 1997 Sep;5(5):293-300. doi: 10.1016/s1063-4584(97)80008-8.

  PMID: 9497936 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Etanercept; Exercise

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Zhiyi Zhang, Ph.D

  First Affiliated Hospital of Harbin Medical University

  STUDY CHAIR

• Yifang Mei, M.D

  First Affiliated Hospital of Harbin Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhiyi Zhang, Ph.D

CONTACT

+86-451-85552350; zhangzhiyi_rheu@163.com

Yifang Mei, M.D

CONTACT

+86-451-85552350; myfyxd@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2016
• First Posted: March 30, 2016
• Study Start: February 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: August 1, 2017
• Last Updated: April 22, 2016

Record last verified: 2016-02

Locations

CN (1)