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Efficacy and tolerability of 5-Loxin®, a novel standardised Boswellia serrata extract in the treatment of Osteoarthritis of knee: a randomised, double blind placebo controlled clinical trial
ISRCTN ISRCTN05212803
DOI 10.1186/ISRCTN05212803
ClinicalTrials.gov identifier
EudraCT number
Public title Efficacy and tolerability of 5-Loxin®, a novel standardised Boswellia serrata extract in the treatment of Osteoarthritis of knee: a randomised, double blind placebo controlled clinical trial
Scientific title
Acronym 5-Loxin® OA clinical trial
Serial number at source IRB#06-001
Study hypothesis 5-Loxin® is a novel Boswellia serrata extract enriched to 30% 3 Acetyl-11-Keto-beta-Boswellic Acid (AKBA) (United States [US] Patent 2004/0073060A1). In carrageenan induced inflammation model, 5-Loxin® confers a significant improvement in paw inflammation in albino Wister rats. Cell based in vitro studies and in vivo experiments conducted in Sprague Dawley rats demonstrate that 5-Loxin® potentially inhibits the pro-inflammatory cytokines such as Tumour Necrotising Factor (TNF)-alpha and Interleukin-1 (IL-1)-beta (yet to be published). Furthermore, affimatrix gene chip analysis demonstrates 5-Loxin® can potentially inhibit the TNF-alpha induced gene expression of Matrix Metalloproteinases (MMPs), adhesion molecules such as Inter-Cellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1) and mediators of apoptosis in human micro vascular endothelial cells. Importantly, extensive studies on acute and dose-dependent sub-chronic safety experiments on rats demonstrate that 5-Loxin® does not exhibit toxic manifestations even at a dose 2000 - 3000 times higher than the Human Equivalence Dose (HED). In addition, 5-Loxin® does not show genotoxicity in the standard Ames bacterial reverse mutation assay (INTOX, study no. 4477/05).

Therefore, in the present investigation, in a double-blind and placebo controlled clinical study we sought to evaluate the efficacy and safety of 5-Loxin® in treatment of Osteoarthritis (OA) of the knee.
Lay summary
Ethics approval This protocol was approved by the Ethics Committee (Institutional Review Board [IRB]) of Alluri Sitarama Raju Academy of Medical Sciences (ASRAM) (India) on the 26th April 2006 (ref: # ASRAM IRB#06-001).
Study design Randomised, placebo controlled trial
Countries of recruitment India
Disease/condition/study domain Osteoarthritis of knee
Participants - inclusion criteria 1. Participants must understand risks and benefits of the protocol and able to give informed consent
2. Male and female subjects of 40 - 80 years of age
3. Females of child bearing potential must agree to use an approved form of birth control and have a negative pregnancy test result
4. Unilateral or bilateral OA of the knee for more than 3 months
5. Visual Analogue Scale (VAS) score during the most painful knee movement between 40 - 70 mm after 7 day withdrawal of usual medication
6. Lequesne's functional index score greater than 7 points after 7 days of withdrawal of usual medication
7. Ability to walk
8. Availability of the duration of the entire study period
Participants - exclusion criteria 1. History of underlying inflammatory arthropathy or severe Rheumatoid Arthritis (RA)
2. Hyperuricemia (greater than 440 umol/L) and/or past history of gout
3. Recent injury in the area affected by OA of the knee (past 4 months) and expectation of surgery in the next 4 months
4. Intra-articular corticosteroid injections within the last 3 months
5. Hypersensitivity to Non-Steroidal Anti-Inflammatory Drugs (NSAIDS), abnormal liver or kidney function tests, history of peptic ulceration and upper Gastrointestinal (GI) haemorrhage, congestive heart failure, hypertension, hyperkalemia
6. Major abnormal findings on complete blood count, history of coagulopathies, haematological or neurological disorders
7. High alcohol intake (greater than 2 standard drinks per day)
8. Pregnant, breastfeeding or planning to become pregnant during the study
9. Use of concomitant prohibited medication other than ibuprofen
10. Obesity: Body Mass Index (BMI) less than 30
11. Systemic Lupus Erythematosis (SLE)
Anticipated start date 06/07/2006
Anticipated end date 04/10/2006
Status of trial Completed
Patient information material
Target number of participants 75 (Seventy five)
Interventions 75 subjects randomised into 3 groups (n = 25):
1. 5-Loxin® 2 x 50 mg/day twice daily (bid)
2. 5-Loxin® 2 x 125 mg/day (bid)
3. Placebo

Ibuprofen was used as a rescue medication for all groups. The study duration was 90 days and evaluations were at baseline, 7, 30, 60 and 90 day.
Primary outcome measure(s) 1. Visual Analog Scale (VAS)
2. Lequesne Functional Index (LFI)
3. Western Ontario and McMaster Universities osteoarthritis index (WOMAC)-pain, WOMAC-stiffness and WOMAC-physical ability

All primary and secondary outcomes are measured at baseline, 7, 30, 60 and 90 days of the study.
Secondary outcome measure(s) 1. TNF-alpha
2. IL-1-beta
3. Interleukin-6 (IL-6)
4. C-Reactive Protein (CRP)
5. Matrix Metelloproteinase-3 (MMP-3)

All primary and secondary outcomes are measured at baseline, 7, 30, 60 and 90 days of the study.
Sources of funding Laila Impex R&D Center (India)
Trial website
Publications Results in http://www.ncbi.nlm.nih.gov/pubmed/18667054
Contact name Dr  Rama Sathish  Andey
  Address Department of Orthopaedics
ASR Academy of Medical Sciences
  City/town Eluru
  Zip/Postcode 534 002
  Country India
  Tel +91 (0)881 224 9361
  Email draramsatish@yahoo.com
Sponsor Laila Impex R&D Center (India)
  Address Unit 1, Phase III
Jawahar Autonagar
  City/town Vijayawada
  Zip/Postcode 520007
  Country India
  Tel +91 (0)866 254 5244
  Email lailarescen@sify.com
Date applied 22/10/2007
Last edited 06/08/2008
Date ISRCTN assigned 22/11/2007
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