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CTRI Number  CTRI/2018/02/011692 [Registered on: 05/02/2018] Trial Registered Retrospectively
Last Modified On: 04/03/2019
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Ayurveda 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   To evaluate the analgesic effect of an aqueous extract of Terminalia chebula, a proprietary chromium complex, and their combination in subjects with joint discomfort. 
Scientific Title of Study   Evaluation of Biomarkers in Patients of Osteoarthritis treated with Terminalia chebula 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
CPT/1, VERSION 1, Dt.25/07/2012. EC/NIMS/1376/2012  Other 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  K SUNIL KUMAR REDDY 
Designation  PhD student 
Affiliation  Nizams Institute of Medical Sciences 
Address  Department of Clinical Pharmacology and Therapeutics Panjagutta Hyderabad Telangana India

Hyderabad
ANDHRA PRADESH
500082
India 
Phone    
Fax    
Email  doc.cuk@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  N Chandrasekhar 
Designation  DM Resident 
Affiliation  Nizams Institute of Medical Sciences 
Address  Department of Clinical Pharmacology and Therapeutics Panjagutta Hyderabad Telangana India

Hyderabad
ANDHRA PRADESH
500082
India 
Phone    
Fax    
Email  csnpru@gmail.com  
 
Details of Contact Person
Public Query  
Name  N Chandrasekhar 
Designation  DM Resident 
Affiliation  Nizams Institute of Medical Sciences 
Address  Department of Clinical Pharmacology and Therapeutics Panjagutta Hyderabad Telangana India

Hyderabad
ANDHRA PRADESH
500082
India 
Phone    
Fax    
Email  csnpru@gmail.com  
 
Source of Monetary or Material Support  
Nizams Institute of Medical Sciences, Panjagutta, Hyderabad 500082, Telangana, India 
 
Primary Sponsor  
Name  Nizams Institute of Medical Sciences 
Address  Panjagutta Hyderabad Telangana India 500082  
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr C Uday Kumar  Nizams Institute of Medical Sciences  Department of Clinical Pharmacology & Therapeutics Nizams Institute of MEdical Sciences Panjagutta Hyderabad 500082
Hyderabad
ANDHRA PRADESH 		 9966611248

doc.cuk@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
NIMS INSTITUTIONAL ETHICS COMMITTEE   Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  (1) ICD-10 Condition: M179||Osteoarthritis of knee, unspecified, Subjects of either gender aged between 40 and 70 years, suffering from joint discomfort for at least 6 months duration, taking only an OTC analgesic medication occasionally.,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  1.Terminalia chebula (TCE) 2.Proprietary Chromium (PCC) Complex (polyphenolic compunds of Phyllanthus emblica fruit extract and purified Shilajit)   Group (A)-1 capsule of TCE 500 mg twice a day and an identical placebo of PCC once daily after food. Group (B)- 1 capsule of TCE 500 mg twice a day and 1 capsule of 400 mcg of PCC once a day after food. Group (C)- 1 capsule of 400 mcg of PCC once a day and an identical placebo of TCE twice daily after food. Group (D)- Identical placebo capsules two in the morning and one in the evening after food. Group (E) -1 capsule of TCE 250 mg twice a day and an identical placebo of PCC once daily after food.  
Comparator Agent  Placebo  Group (A)-1 capsule of TCE 500 mg twice a day and an identical placebo of PPC once daily after food. Group (B)- 1 capsule of TCE 500 mg twice a day and 1 capsule of 400 mcg of PPC once a day after food. Group (C)- 1 capsule of 400 mcg of PCC once a day and an identical placebo of Terminalia chebula twice daily after food. Group (D)- Identical placebo capsules two in the morning and one in the evening after food. Group (E) -1 capsule of TCE 250 mg twice a day and an identical placebo of PCC once daily after food.  
 
Inclusion Criteria  
Age From  40.00 Year(s)
Age To  70.00 Year(s)
Gender  Both 
Details  Subjects of either gender aged between 40 and 70 years, suffering from joint discomfort for at least 6 months duration, taking only an OTC analgesic medication occasionally and meeting the American Rheumatism Association(ARA) functional class I to III and radiological evidence of osteoarthritis, patients who have grade II to IV of the Kellgren and Lawrence scale in the knee joint X-ray and who record baseline pain scores of at least 40 mm on the Visual Analogue Scale(VAS), monitored at baseline visit, subjects agreeing to discontinue any use of analgesics during the study. 
 
ExclusionCriteria 
Details  Patients with severe osteoarthritis (ARA functional class IV), Patients with radiological grading - Kellgren and Lawrence scale ranging from grade 0 to grade I, patients on alternative system of medicine, any psychiatric disorder or who have been using systemic/intra-articular steroids within 12 weeks and hyaluronic acid in the last 9 months, or potential candidates for imminent joint replacement, Patients with uncontrolled hypertension or diabetes, hepatic or renal impairment, pregnant or lactating females, or with a recent trauma of the involved knee. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Case Record Numbers 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
Modified Western Ontario and McMaster Universities (mWOMAC) Index is a disease specific outcome measure for osteoarthritis. It has three subscales assessing, Pain –A, Stiffness-B and Physical Function for Disability-C. Primary outcome is the reduction in modified WOMAC total score (A+B+C) from baseline to the end of treatment at week 12.   week 4, week 8 and week 12.  
 
Secondary Outcome  
Outcome  TimePoints 
VAS based assessment of Pain,Disability, and Stiffness subscales.
Knee Swelling Index as measured by signal joint knee circumference.
Use of rescue medication in all treatment groups.
Physician global assessment-characterized by 5 categories:Excellent- complete relief of symptoms;Good–partial relief of symptoms;Fair–minimal relief of symptoms;poor–no relief of symptoms;very poor–worsening of symptoms 		 week 4, week 8 and week 12.  
 
Target Sample Size   Total Sample Size="100"
Sample Size from India="100" 
Final Enrollment numbers achieved (Total)= "100"
Final Enrollment numbers achieved (India)="100" 
Phase of Trial   N/A 
Date of First Enrollment (India)   22/07/2013 
Date of Study Completion (India) 28/04/2014 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="2"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   None yet 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary   Joint discomfort may be an early indication of onset of osteoarthritis, which is a non-inflammatory degenerative disorder of joints characterized by progressive deterioration of the articular cartilage and formation of new bone (osteophytes). The use of NSAIDs for symptomatic relief of joint discomfort is limited by their gastrointestinal adverse effects. Terminalia chebula is an Ayurvedic preparation that has shown analgesic and anti-inflammatory effect in  animals. A Proprietary Chromium Complex (PCC) was also shown to be efficacious in reducing pain in dogs with moderate osteoarthritis. Hence, the current study was planned to evaluate the analgesic property of an aqueous extract of T. chebula (TCE), a combination of TCE and PCC and PCC alone on outcome parameters of efficacy and safety in patients with discomfort of the knee joint. 

While nonsteroidal anti-inflammatory drugs(NSAIDs) are effective for the treatment of pain and are overall well tolerated, their use is associated with potentially severe adverse effects. Gastrointestinal (GI) complications from NSAIDs include dyspepsia, ulcers and bleeding. Epidemiologic studies suggest that use of NSAIDs increases the risk of GI complications two to six times. A safer alternative treatment would therefore be beneficial in such cases. Natural products derived from plants offer such an alternative. Terminalia chebula is a plant commonly used in Ayurvedic medicine for the treatment of arthritis, gout, paralysis. Both anecdotal evidence and recent studies have implicated the potential of this herbal remedy for the treatment of painful, chronic arthritic type conditions in experimental models. Animal studies have demonstrated the anti-inflammatory activity  of the ethanolic extract of T.chebula fruits and the probable mechanism of action  was postulated to be due to inhibition of COX-1, COX-2 and 5-LOX enzymes. Another mechanism which can be attributed to  Terminalia chebula’santi-inflammatory action could be down regulation of NFkB. Only one human study has demonstrated the anti-inflammatory properties of a polyherbal formulation for allergic rhinitis, containing T.chebula as one of several ingredients.

Proprietary Chromium Complex (PCC)  is a complex of Chromium III with the polyphenolic compunds of Phyllanthus emblica fruit extract and purified Shilajit, a natural product from the Himalays, containing dibenzo-α-pyrones (DBPs), DBP-chromoproteins and fulvic acids. A recent study has shown that this complex decreased pain associated with osteoarthritis in dogs. No human clinical studies of T. chebula or PCC in subjects with joint pain and discomfort have been reported so far. Thus, the present clinical study was aimed at evaluating the efficacy and safety of an aqueous extract of Terminalia chebula at two different doses, Proprietary Chromium Complex alone and a combination of both in human volunteers with joint discomfort.

A total of 100 patients with knee joint discomfort were randomized to either of the five treatment groups -TCE500 mg BID, TCE 500 mg BID+  PCC 400mcg OD, PCC 400mcgOD alone, placebo and TCE 250 mg BID, in a double blinded manner. Assessment of symptoms of knee joint pain& discomfort was done by modified Western Ontario and McMaster Universities Arthritis Index (mWOMAC) and Knee Swelling Index (KSI), Visual Analogue Scale (VAS) was used for subjective assessment of pain, stiffness and disability. Tolerability was assessed by the incidence of adverse effects in the treatment groups. The duration of the study was 12 weeks.

 
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