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 | https://doi.org/10.1186/ISRCTN05212803 |
| Secondary identifying numbers | IRB#06-001 |
- Submission date
- 22/10/2007
- Registration date
- 22/11/2007
- Last edited
- 06/08/2008
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Rama Sathish Andey
Scientific
Scientific
Department of Orthopaedics
ASR Academy of Medical Sciences
Eluru
534 002
India
| Phone | +91 (0)881 224 9361 |
|---|---|
| draramsatish@yahoo.com |
Study information
| Study design | Randomised, placebo controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | |
| Study acronym | 5-Loxin® OA clinical trial |
| Study objectives | 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(s) | 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). |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | 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 study start date | 06/07/2006 |
| Completion date | 04/10/2006 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 75 (Seventy five) |
| Key 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 |
| Key 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) |
| Date of first enrolment | 06/07/2006 |
| Date of final enrolment | 04/10/2006 |
Locations
Countries of recruitment
- India
Study participating centre
Department of Orthopaedics
Eluru
534 002
India
534 002
India
Sponsor information
Laila Impex R&D Center (India)
Industry
Industry
Unit 1, Phase III
Jawahar Autonagar
Vijayawada
520007
India
| Phone | +91 (0)866 254 5244 |
|---|---|
| lailarescen@sify.com | |
"ROR" |
https://ror.org/05q6g7072 |
Funders
Funder type
Industry
Laila Impex R&D Center (India)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | Results | 01/04/2008 | Yes | No |
