Effects of Dietary Supplement on Osteoarthritis

NCT03665116 | Unknown

• 1 other identifier: 20190018
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the effects arginine on osteoarthritis (OA) in adults. Participants will be randomly divided into two groups, taking arginine and nothing, respectively. Outcomes will be evaluated by lab test results on OA joint cartilage and self-administered questionnaires. The hypothesis is that arginine can slow down or reverse OA.

Conditions

Knee Osteoarthritis

Keywords

Gene expression; Molecular phenotype; Osteoarthritis severity grading

Outcome Measures

Primary Outcomes (1)

• Target Gene Expressions in Osteoarthritic Knee Cartilage after 6 Months of Supplementation

  After participants have been taking arginine or nothing for 6 months, and cartilage tissue has been obtained during participants' total knee replacement surgery, target gene expressions in cartilage are measured with quantitative polymerase chain reaction (qPCR). Genes include cartilage degradation enzymes - matrix metallopeptidase 13 (MMP13), cathepsin K (CTSK), cathepsin B (CTSB), and cartilage syntheses genes - aggrecan (ACAN) and type II collagen (CTXII).

  up to 20 months

Secondary Outcomes (7)

• OA Severity Grade of Osteoarthritic Knee Cartilage after 6 Months of Supplementation

  up to 6 months

• WOMAC to Measure Changes in Joint Pain and Function between baseline and at 6 Months

  at baseline and in 6 months

• WOMAC to Measure Changes in Joint Pain and Function between baseline and at 6 Months Post-surgery

  at baseline and 6 months post-surgery

• WOMAC to Measure Changes in Joint Pain and Function between baseline and at 12 Months Post-surgery

  at baseline and 12 months post-surgery

• SF-36 to Measure Changes in Physical and Mental Function between baseline and at 6 Months

  at baseline and in 6 months

Study Arms (2)

Arginine

EXPERIMENTAL

L-arginine 1.5 g capsule by mouth, once daily for 6 months

Dietary Supplement: L-arginine

No Intervention

NO INTERVENTION

no supplement for 6 months

Interventions

L-arginine DIETARY_SUPPLEMENT

L-arginine capsule

Arginine

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Undergoing total knee replacement surgery in 6 months due to primary knee OA
• Must be ambulatory
• Must live in 50 kilometers perimeter of St. John's, capital city of Newfoundland and Labrador, Canada

You may not qualify if:

• Clinical diagnosis of secondary OA or inflammatory arthritis
• Cod liver oil supplementation within 6 months
• Supplementation containing arginine within 6 months
• Osteoporotic fracture, previous knee surgery or arthroscopy within 6 months
• Use of bisphosphonates within 2 years
• Use of Intra-articular viscosupplementation or platelet rich plasma at any point

Sponsors & Collaborators

• Memorial University of Newfoundland: lead
• Ocean Frontier Institute: collaborator

Study Sites (1)

Total Joint Assessment Clinic

St. John's, Newfoundland and Labrador, A1A 3Z9, Canada

Location

Related Publications (29)

• Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, Laslett LL, Jones G, Cicuttini F, Osborne R, Vos T, Buchbinder R, Woolf A, March L. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014 Jul;73(7):1323-30. doi: 10.1136/annrheumdis-2013-204763. Epub 2014 Feb 19.

  PMID: 24553908 BACKGROUND

• Sharif B, Kopec J, Bansback N, Rahman MM, Flanagan WM, Wong H, Fines P, Anis A. Projecting the direct cost burden of osteoarthritis in Canada using a microsimulation model. Osteoarthritis Cartilage. 2015 Oct;23(10):1654-63. doi: 10.1016/j.joca.2015.05.029. Epub 2015 Jun 5.

  PMID: 26050868 BACKGROUND

• Guermazi A, Roemer FW, Felson DT, Brandt KD. Motion for debate: osteoarthritis clinical trials have not identified efficacious therapies because traditional imaging outcome measures are inadequate. Arthritis Rheum. 2013 Nov;65(11):2748-58. doi: 10.1002/art.38086. No abstract available.

  PMID: 23861096 BACKGROUND

• Grant WB, Schwalfenberg GK, Genuis SJ, Whiting SJ. An estimate of the economic burden and premature deaths due to vitamin D deficiency in Canada. Mol Nutr Food Res. 2010 Aug;54(8):1172-81. doi: 10.1002/mnfr.200900420.

  PMID: 20352622 BACKGROUND

• Schwalfenberg G. Not enough vitamin D: health consequences for Canadians. Can Fam Physician. 2007 May;53(5):841-54.

  PMID: 17872747 BACKGROUND

• McAlindon TE, Felson DT, Zhang Y, Hannan MT, Aliabadi P, Weissman B, Rush D, Wilson PW, Jacques P. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study. Ann Intern Med. 1996 Sep 1;125(5):353-9. doi: 10.7326/0003-4819-125-5-199609010-00001.

  PMID: 8702085 BACKGROUND

• Bergink AP, Uitterlinden AG, Van Leeuwen JP, Buurman CJ, Hofman A, Verhaar JA, Pols HA. Vitamin D status, bone mineral density, and the development of radiographic osteoarthritis of the knee: The Rotterdam Study. J Clin Rheumatol. 2009 Aug;15(5):230-7. doi: 10.1097/RHU.0b013e3181b08f20.

  PMID: 19654490 BACKGROUND

• Ding C, Cicuttini F, Parameswaran V, Burgess J, Quinn S, Jones G. Serum levels of vitamin D, sunlight exposure, and knee cartilage loss in older adults: the Tasmanian older adult cohort study. Arthritis Rheum. 2009 May;60(5):1381-9. doi: 10.1002/art.24486.

  PMID: 19404958 BACKGROUND

• Abu el Maaty MA, Hanafi RS, El Badawy S, Gad MZ. Association of suboptimal 25-hydroxyvitamin D levels with knee osteoarthritis incidence in post-menopausal Egyptian women. Rheumatol Int. 2013 Nov;33(11):2903-7. doi: 10.1007/s00296-012-2551-9. Epub 2012 Nov 4.

  PMID: 23124694 BACKGROUND

• Heidari B, Heidari P, Hajian-Tilaki K. Association between serum vitamin D deficiency and knee osteoarthritis. Int Orthop. 2011 Nov;35(11):1627-31. doi: 10.1007/s00264-010-1186-2. Epub 2010 Dec 30.

  PMID: 21191580 BACKGROUND

• Sanghi D, Mishra A, Sharma AC, Singh A, Natu SM, Agarwal S, Srivastava RN. Does vitamin D improve osteoarthritis of the knee: a randomized controlled pilot trial. Clin Orthop Relat Res. 2013 Nov;471(11):3556-62. doi: 10.1007/s11999-013-3201-6. Epub 2013 Aug 1.

  PMID: 23904246 BACKGROUND

• McAlindon T, LaValley M, Schneider E, Nuite M, Lee JY, Price LL, Lo G, Dawson-Hughes B. Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial. JAMA. 2013 Jan 9;309(2):155-62. doi: 10.1001/jama.2012.164487.

  PMID: 23299607 BACKGROUND

• Arden NK, Cro S, Sheard S, Dore CJ, Bara A, Tebbs SA, Hunter DJ, James S, Cooper C, O'Neill TW, Macgregor A, Birrell F, Keen R. The effect of vitamin D supplementation on knee osteoarthritis, the VIDEO study: a randomised controlled trial. Osteoarthritis Cartilage. 2016 Nov;24(11):1858-1866. doi: 10.1016/j.joca.2016.05.020. Epub 2016 Jun 2.

  PMID: 27264058 BACKGROUND

• Jin X, Jones G, Cicuttini F, Wluka A, Zhu Z, Han W, Antony B, Wang X, Winzenberg T, Blizzard L, Ding C. Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis: A Randomized Clinical Trial. JAMA. 2016 Mar 8;315(10):1005-13. doi: 10.1001/jama.2016.1961.

  PMID: 26954409 BACKGROUND

• McAlindon TE, Jacques P, Zhang Y, Hannan MT, Aliabadi P, Weissman B, Rush D, Levy D, Felson DT. Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis? Arthritis Rheum. 1996 Apr;39(4):648-56. doi: 10.1002/art.1780390417.

  PMID: 8630116 BACKGROUND

• Brand C, Snaddon J, Bailey M, Cicuttini F. Vitamin E is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study. Ann Rheum Dis. 2001 Oct;60(10):946-9. doi: 10.1136/ard.60.10.946.

  PMID: 11557651 BACKGROUND

• Wluka AE, Stuckey S, Brand C, Cicuttini FM. Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2 year double blind randomized placebo controlled study. J Rheumatol. 2002 Dec;29(12):2585-91.

  PMID: 12465157 BACKGROUND

• Morris SM Jr. Recent advances in arginine metabolism: roles and regulation of the arginases. Br J Pharmacol. 2009 Jul;157(6):922-30. doi: 10.1111/j.1476-5381.2009.00278.x. Epub 2009 Jun 5.

  PMID: 19508396 BACKGROUND

• Zhang W, Sun G, Likhodii S, Liu M, Aref-Eshghi E, Harper PE, Martin G, Furey A, Green R, Randell E, Rahman P, Zhai G. Metabolomic analysis of human plasma reveals that arginine is depleted in knee osteoarthritis patients. Osteoarthritis Cartilage. 2016 May;24(5):827-34. doi: 10.1016/j.joca.2015.12.004. Epub 2015 Dec 18.

  PMID: 26708258 BACKGROUND

• Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842-56. doi: 10.1093/ajcn/69.5.842.

  PMID: 10232622 BACKGROUND

• Vukic M, Neme A, Seuter S, Saksa N, de Mello VD, Nurmi T, Uusitupa M, Tuomainen TP, Virtanen JK, Carlberg C. Relevance of vitamin D receptor target genes for monitoring the vitamin D responsiveness of primary human cells. PLoS One. 2015 Apr 13;10(4):e0124339. doi: 10.1371/journal.pone.0124339. eCollection 2015.

  PMID: 25875760 BACKGROUND

• Aref-Eshghi E, Liu M, Harper PE, Dore J, Martin G, Furey A, Green R, Rahman P, Zhai G. Overexpression of MMP13 in human osteoarthritic cartilage is associated with the SMAD-independent TGF-beta signalling pathway. Arthritis Res Ther. 2015 Sep 23;17(1):264. doi: 10.1186/s13075-015-0788-x.

  PMID: 26395178 BACKGROUND

• Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D, van den Berg WB. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage. 2006 Jan;14(1):13-29. doi: 10.1016/j.joca.2005.07.014. Epub 2005 Oct 19.

  PMID: 16242352 BACKGROUND

• Perez-Portela R, Riesgo A. Optimizing preservation protocols to extract high-quality RNA from different tissues of echinoderms for next-generation sequencing. Mol Ecol Resour. 2013 Sep;13(5):884-9. doi: 10.1111/1755-0998.12122. Epub 2013 May 20.

  PMID: 23683108 BACKGROUND

• Aref-Eshghi E, Liu M, Razavi-Lopez SB, Hirasawa K, Harper PE, Martin G, Furey A, Green R, Sun G, Rahman P, Zhai G. SMAD3 Is Upregulated in Human Osteoarthritic Cartilage Independent of the Promoter DNA Methylation. J Rheumatol. 2016 Feb;43(2):388-94. doi: 10.3899/jrheum.150609. Epub 2015 Dec 15.

  PMID: 26669923 BACKGROUND

• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001 Dec;25(4):402-8. doi: 10.1006/meth.2001.1262.

  PMID: 11846609 BACKGROUND

• Zhai G, Dore J, Rahman P. TGF-beta signal transduction pathways and osteoarthritis. Rheumatol Int. 2015 Aug;35(8):1283-92. doi: 10.1007/s00296-015-3251-z. Epub 2015 Mar 15.

  PMID: 25773660 BACKGROUND

• Zhang W, Likhodii S, Aref-Eshghi E, Zhang Y, Harper PE, Randell E, Green R, Martin G, Furey A, Sun G, Rahman P, Zhai G. Relationship between blood plasma and synovial fluid metabolite concentrations in patients with osteoarthritis. J Rheumatol. 2015 May;42(5):859-65. doi: 10.3899/jrheum.141252. Epub 2015 Mar 1.

  PMID: 25729031 BACKGROUND

• Zhang W, Sun G, Aitken D, Likhodii S, Liu M, Martin G, Furey A, Randell E, Rahman P, Jones G, Zhai G. Lysophosphatidylcholines to phosphatidylcholines ratio predicts advanced knee osteoarthritis. Rheumatology (Oxford). 2016 Sep;55(9):1566-74. doi: 10.1093/rheumatology/kew207. Epub 2016 May 9.

  PMID: 27160277 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Arginine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Guangju Zhai, PhD

  Memorial University of Newfoundland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: September 11, 2018
• Study Start: March 5, 2019
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2024
• Last Updated: July 14, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)