title: Treatment with 4Jointz reduces knee pain over 12 weeks of treatment in patients with clinical knee osteoarthritis: a randomised controlled trial.
abstract: OBJECTIVE
  To assess the efficacy of thrice daily topical 4Jointz utilizing Acteev technology (a combination of a standardized comfrey extract and a pharmaceutical grade tannic acid, 3.5 g/day) on osteoarthritic knee pain, markers of inflammation and cartilage breakdown over 12 weeks.
  
  
  METHODS
  Adults aged 50-80 years (n = 133) with clinical knee OA were randomised to receive 4Jointz or placebo in addition to existing medications. Pain and function were measured using a visual analogue scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) scale at baseline, 4, 8 and 12 weeks. Inflammation was measured analysing IL-6 expression and CTX-2 presence as representative for cartilage breakdown using ELISA, at baseline and 12 weeks.
  
  
  RESULTS
  Pain scores significantly reduced in the group who received 4Jointz compared to the group who received placebo after 12 weeks using both the VAS (-9.9 mm, P = 0.034) and the KOOS pain scale (+5.7, P = 0.047). Changes in IL-6 and CTX-2 were not significant (-0.04, P = 0.5; -0.01, P = 0.68). Post-hoc analyses suggested that treatment may be most effective in women (VAS -16.8 mm, P = 0.008) and those with milder radiographic osteoarthritis (OA) (VAS -16.1 mm, P = 0.009). Rates of adverse events were similar in both groups, excepting local rash that was more common amongst participants receiving 4Jointz (21% vs 1.6%, IRR 13.2, P = 0.013), but only 26% (n = 4) of participants with rashes discontinued treatment. There were no changes in systemic blood results.
  
  
  CONCLUSIONS
  Topical treatment using 4Jointz reduced pain but had no effect on inflammation or cartilage breakdown over 12 weeks of treatment.
  
  
  BACKGROUND
  Australia and New Zealand Clinical Trials registry ACTRN12610000877088.
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Australia. Laura.Laslett@utas.edu.au
authors.forename: L L
authors.initials: LL
authors.lastname: Laslett
authors.forename: S J
authors.initials: SJ
authors.lastname: Quinn
authors.forename: E
authors.initials: E
authors.lastname: Darian-Smith
authors.forename: M
authors.initials: M
authors.lastname: Kwok
authors.forename: T
authors.initials: T
authors.lastname: Fedorova
authors.forename: H
authors.initials: H
authors.lastname: Körner
authors.forename: E
authors.initials: E
authors.lastname: Steels
authors.forename: L
authors.initials: L
authors.lastname: March
authors.forename: G
authors.initials: G
authors.lastname: Jones
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000627:therapeutic use*; D020844:Comfrey / Q000737:chemistry*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010146:Pain / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D059408:Pain Management; D010147:Pain Measurement; D010936:Plant Extracts / Q000627:therapeutic use*; D020127:Recovery of Function; D013634:Tannins / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D004338:Drug Combinations; D010936:Plant Extracts; D013634:Tannins