Contact information
Type
Scientific
Primary contact
Dr Rama Sathish Andey
ORCID ID
Contact details
Department of Orthopaedics
ASR Academy of Medical Sciences
Eluru
534 002
India
+91 (0)881 224 9361
draramsatish@yahoo.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
IRB#06-001
Study information
Scientific title
Acronym
5-Loxin® OA clinical trial
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.
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
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Osteoarthritis of knee
Intervention
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.
Intervention type
Drug
Phase
Not Specified
Drug names
5-Loxin® (Boswellia serrata extract)
Primary outcome measure
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 measures
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.
Overall trial start date
06/07/2006
Overall trial end date
04/10/2006
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
75 (Seventy five)
Participant 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)
Recruitment start date
06/07/2006
Recruitment end date
04/10/2006
Locations
Countries of recruitment
India
Trial participating centre
Department of Orthopaedics
Eluru
534 002
India
Sponsor information
Organisation
Laila Impex R&D Center (India)
Sponsor details
Unit 1
Phase III
Jawahar Autonagar
Vijayawada
520007
India
+91 (0)866 254 5244
lailarescen@sify.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Laila Impex R&D Center (India)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
Results in http://www.ncbi.nlm.nih.gov/pubmed/18667054
Publication citations
-
Results
Sengupta K, Alluri KV, Satish AR, Mishra S, Golakoti T, Sarma KV, Dey D, Raychaudhuri SP, A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee., Arthritis Res. Ther., 2008, 10, 4, R85, doi: 10.1186/ar2461.