title: Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine, for patients with osteoarthritis of the knee: a multi-site, randomized, double-blind, placebo-controlled phase II clinical trial.
abstract: OBJECTIVE
  To examine the efficacy and safety of Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine (TCM), in patients with knee osteoarthritis (OA).
  
  
  METHODS
  A multi-site, randomized, double-blind, placebo-controlled phase II dose-escalation clinical trial was conducted. Eligible patients who fulfilled American College of Rheumatology criteria were randomized to receive either HLXL or placebo. Clinical assessments included measurement of knee pain and function with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), patient global assessment (PGA), and knee pain scores every 2 weeks. A Data and Safety Monitoring Board (DSMB) was established to review the data for ensuring the quality of the trial.
  
  
  RESULTS
  In the first stage, 28 participants were randomized to receive either low-dose HLXL-Dan (2400 mg/day) or placebo for 6 weeks. The results showed no statistical difference between the two groups. The study was then re-designed following the recommendation of DSMB. Ninety-two patients were enrolled in the second stage and were randomized to receive either high-dose HLXL-Dan (4000 mg/day for week 1-2, and 5600 mg/day for week 3-8) or placebo for 8 weeks. All outcome assessments showed significant improvements for both groups after 8 weeks but no significant between-group differences. The change (mean ± SD) of WOMAC pain and WOMAC function scores of HLXL and placebo group after 8 weeks were -1.2 ± 1.7 vs -1.4 ± 1.5, and -1.1 ± 1.6 vs -1.3 ± 1.5 respectively. No serious adverse events were reported.
  
  
  CONCLUSIONS
  Although safe to use, an 8-week treatment of HLXL-Dan was not superior to placebo for reduction in pain or functional improvement in patients with knee OA.
  
  
  BACKGROUND
  Clinicaltrials.gov (NCT00755326).
authors.affiliation: Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, USA; School of Chinese Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address: lxlao1@hku.hk.
authors.forename: L
authors.initials: L
authors.lastname: Lao
authors.affiliation: Division of Rheumatology & Clinical Immunology, Department of Medicine, School of Medicine, University of Maryland, Baltimore, USA. Electronic address: mhochber@medicine.umaryland.edu.
authors.forename: M
authors.initials: M
authors.lastname: Hochberg
authors.affiliation: Mailman Research Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA. Electronic address: dlee@mclean.harvard.edu.
authors.forename: D Y W
authors.initials: DYW
authors.lastname: Lee
authors.affiliation: Department of Epidemiology and Public Health, School of Medicine, University of Maryland, Baltimore, USA. Electronic address: adele.gilpin@gmail.com.
authors.forename: A M K
authors.initials: AMK
authors.lastname: Gilpin
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: hfong@uic.edu.
authors.forename: H H S
authors.initials: HHS
authors.lastname: Fong
authors.affiliation: Department of Epidemiology and Public Health, School of Medicine, University of Maryland, Baltimore, USA. Electronic address: PLANGENB@epi.umaryland.edu.
authors.forename: P
authors.initials: P
authors.lastname: Langenberg
authors.affiliation: Department of Family and Community Medicine, School of Medicine, University of Maryland, Baltimore, USA. Electronic address: KChen@som.umaryland.edu.
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address: edmundli@cuhk.edu.hk.
authors.forename: E K
authors.initials: EK
authors.lastname: Li
authors.affiliation: Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address: lstam@cuhk.edu.hk.
authors.forename: L S
authors.initials: LS
authors.lastname: Tam
authors.affiliation: Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, USA. Electronic address: BBerman@som.umaryland.edu.
authors.forename: B
authors.initials: B
authors.lastname: Berman
mesh_terms: D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008516:Medicine, Chinese Traditional; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D016896:Treatment Outcome
chemical_list: D004365:Drugs, Chinese Herbal; C547651:huo luo xiao ling dan
keywords: Chinese herbs; Huo-Luo-Xiao-Ling-Dan; Knee osteoarthritis; Randomized controlled trial; Traditional Chinese medicine