Research Experience (Major Projects)
A study of ‘polyarthritides’ with
special reference to rheumatoid arthritis (RA).
study was conducted in Armed Forces Medical College
and Command Hospital, Pune & Military Hospital,
Belgaum during 1981-87. Begun as a cross-sectional
clinical case study, a cohort of patients with
atypical early seronegative polyarthritis were
immunologic, radiologic and epidemiologic aspects,
relevant to Indian scenario, of over 200 patients,
mostly servicemen, were analysed in detail.
clinical syndrome of RA-seronegative spondarthritis
(SSA) overlap in young servicemen was defined.
Subsequently, HLA A and B profiles, using microlyphocytotoxicity
technique on Terasaki plates, were defined in
patients with SSA and healthy controls.
findings of the initial 50 patients were described
in a dissertation submitted to the University
of Pune for the award of MD (general medicine).
Further data and results were presented in various
national meetings and published.
Memorial Award for the best research paper
at the national meeting of the Association
of Physicians of India, Madurai, 1987.
E. Merck Award for
the best research paper at the national
meeting of the Association of Physicians
of India, Pune, 1988
A study of neurological complications of hemorrhagic
study was begun during an epidemic of conjunctivitis
in Armed Forces Medical College and Command Hospital,
Pune in 1981.The cause was later identified as
Enterovirus-70. Number of patients developed polyradiculoneuropathy
with dysautonomias akin to Guillain-Barre syndrome;
detail clinical and serological, including CSF,
studies were undertaken. A cohort of patients
was followed up.
A new neurological profile as a complication of
Enterovirus-70 was defined.
results were published (J of Tropical & Geographical
Medicine 1986, V 38: 197-202), and received wide
spread attention from numerous medical centers
in the world.
study of arthritis and rheumatism in the community
through medical camps
of cost diagnostic evaluation and therapy guidance
to over 6000 patients has been provided in medical
camps conducted in the Pune metropolis and neighboring
rural areas and towns from 1992 to 1996.Detail
clinical records were maintained.
indigenously-designed-software-based patient database
was created; probably for the first time in India.
The clinical results, including the design of
the arthritis soft-ware program, were presented
in numerous national and international meetings.
public health education campaign, as part and
parcel of the arthritis camps, was also organized
in conjunction with the School of Health Sciences,
University of Pune, in the Pune metropolis, in
IRA gold medal and the BOOTS best research
paper award at the national conference
of the Indian Rheumatism Association ,
APLAR travel fellowship
to present the some of the data from medical
camps in the APLAR (Asia-Pacific League
of Associations for Rheumatology) Congress,
Bali, Indonesia, 1992.
community oriented program for control of rheumatic
diseases (COPCORD) under the auspices of WHO-ILAR-APLAR
maiden COPCORD in India was launched in village
Bhigwan (Pune District)
in Feb 1996.The COPCORD
epidemiological model envisages measurement of
the rheumatic musculoskeletal (RMSD) burden, and
not necessarily well-defined rheumatic syndromes,
in the community. In the first stage (3 phases)-house
to house survey, identification of rheumatic patients
and rheumatologic evaluation is completed. Stages
2 and 3 include health education, identification
of risk factors and control strategies.
Bhigwan COPCORD model has successfully taken cognizance
of the Indian traditions and life styles and created
an extensive community oriented data base. The
latter includes details on pain, disability, concepts,
beliefs and perceptions of the Bhigwan people.
initial Bhigwan survey interviewed about 7000
village residents by validated questionnaires
served by trained village volunteers; 774 patients
were identified. Besides clinical evaluation,
diagnostic laboratory and radiological work up
was also set up.
A sera bank from the village patients was created
in Center for Rheumatic Diseases (CRD), Pune.
Till date, patients have been followed up every
3-4 weeks in a planned schedule.
In 1999, a resurvey of the village adult population
and incidence data from this rural study has been
presented in numerous national and international
meetings, and published. An unusually high prevalence
of inflammatory arthritis, RA in particular, has
been found. The study has also established the
predominant nature of RMSD in the community. Ill
defined soft tissue aches and pains and soft tissue
rheumatism are the dominant problems of the community.
The COPCORD Bhigwan is the first prospective study
of its kind in the World, and is now extended
WHO while launching the Bone and Joint Decade
in Jan 2000, has listed the COPCORD Bhigwan study
in its Global data inventory and has used its
data to represent the South East Asian scenario
in its publication, a Technical Research Series,
on the global burden of musculoskeletal diseases
in the new millennium. .
Under this program, HLA DRB1 analysis of the patients
with inflammatory arthritis has been undertaken
in collaboration with Univ of Manchester, UK.
The results are in total variance with what is
generally believed to the case e.g. there is no
association of RA from this rural community with
on the concepts, beliefs and lack of scientific
information in the community, the WHO has sponsored
a publication of a health education booklet for
free circulation in the region. The book, in the
regional language, contains information on arthritis
in a question-answer format and is illustrated
of anti-nuclear antibodies (ANA) from serum and
filter paper blood clots (FPBC) using indirect
immunofluorescence (IIF) has been the gold standard
for detection of ANA from patients with systemic
connective tissue diseases (CTD) but is a technically
cumbersome and expensive test besides being sparsely
available in India. IIE is a simpler method using
color enzymes that can demonstrate ANA under light
microscope but has not found popular use anywhere
in the World. FPBC, obtained through finger/ heel
pricking, have been used in epidemiological studies,
mostly in pediatric diseases (e.g. poliomyelitis)
to collect blood samples for serodiagnosis.
project was begun in 1992 to standardize the technique
of ANA detection by IIE using serum and FPBC from
patients with CTD.A protocol was designed to randomly
and blindly compare the results of IIE with those
of the IIF. More than 270 paired samples were
collected both from patients and healthy controls.
A pilot study was undertaken in the Dept of Rheumatology,
The St George Hospital, Sydney, Australia as part
of the APLAR study grant award 1992, to standardize
the extraction of serum equivalent elute from
FPBC, and then detect ANA using IIE. The results
were comparable with those of IIF on FPBC elutes.
results demonstrated that IIE is a viable option
to IIF for detection of ANA. The use of FPBC to
collect samples and then apply IIE for detecting
ANA will enhance the feasibility of population
surveys on uncommon diseases like CTD in countries
of validated quality of life (QOL) instruments
to evaluate the functional outcome in diseases
like RA and OA.
popular Stanford modified HAQ (health assessment
questionnaire) was chosen for modification as
per the Indian style of living and customs. The
basic structure covering the 8 activities was
preserved, but the questions were changed to address
the Indian issues of dressing, traveling, working
and activities of daily living including toilet
use. A consensus approach was used, and after
pilot testing in a cohort of patients and healthy
people the Indian HAQ was validated systematically
in cross-sectional evaluation of patients of RA,
and in a long term drug trial study using DMARDs.
The Indian HAQ was further applied to patients
with varying types of rheumatic disorders from
a rural population (see COPCORD Bhigwan study
above).This is the first Indian HAQ which has
now been used in numerous drug trials in India,
notably randomized controlled studies of meloxicam
and celecoxib. This HAQ is also being used routinely
in the referral practice at the CRD, Pune, since
1995; over 5000 patients of RA have been evaluated
WOMAC (Western Ontario McMaster University, Canada)
instrument for OA of the hips and knees was selected
for modification and later validation. While the
pain and stiffness component of the parent index
was unchanged, the ‘physical difficulty’
component was changed to suit the Indian life
style, especially of squatting and sitting cross
legged. The Indian WOMAC has been successfully
used in numerous drug trials using Ayurvedic medication,
and selective COX-2 inhibitors.
drug studies of an Ayurvedic formulation in patients
with RA and OA.
literature search to study the role of Ayurveda
in diagnosis and management of arthritis was undertaken,
and modern experimental evidence on medicinal
plants was evaluated. The need to validate ancient
medicines which are still in popular use in the
modern context was recognized. A concept of modern
medicine-Ayurveda interface was developed and
presented in a meeting of Ayurvedic scholars in
the Pune Univ in 1994.
an Ayurvedic anti-arthritis formulation derived
from well known Ayurvedic medicinal plants’
extracts (ashwagandha, gugulla, ginger, turmeric),
had been identified by Prof B Patwardhan, School
of Health Sciences, Pune University and meticulously
standardized by modern pharma techniques. RA1
was also proven to be extremely safe in both acute
and chronic animal toxicity models.
an Indo-US collaboration, an international standard
protocol driven randomized double blind (RDB)
drug trials comparing RA-1(an Ayurvedic formulation)
with identical placebo in patients with rheumatoid
arthritis (RA) and osteoarthritis (OA) were conducted
in CRD, Pune during the period 1994-1999. The
drug trial protocols were co-designed with Prof
Polisson, Arthritis Unit, Massachusetts General
Hospital and Howard Medical School, USA. The entire
project was sponsored by Ayurcore Inc., USA.
eligible patients with active RA were randomized
to receive RA 1 or placebo in a RDB drug trial
of 16 weeks duration; later the patients were
followed up in an open label phase for over 3
years.RA-1 showed impressive efficacy and excellent
safety. The trial results were selected to be
poster presented in the annual congress of the
American College of Rheumatology (ACR) 1996, and
published in peer reviewed journal (J Rheum 2000).
The research module used and the subject of Ayurveda
and arthritis was also published in the Rheum
Clinics of N America 2000.
eligible patients with moderately severe symptomatic
OA knees were randomized to receive RA 11(an augmented
form of RA 1) or placebo in a RDB drug trial of
32 week duration. The results demonstrated a highly
significant superior efficacy for RA 11 in reducing
pain and improving quality of life functions related
to knee joints (see Indian modified WOMAC described
above).RA 11 had an excellent safety profile.
Urinary cortisol studies proved that RA 11 did
not contain any steroid moiety. The trial results
were selected to be poster presented in annual
congress of ACR 1998.
drug trial studies of meloxicam, celecoxib and
advent of selective COX 2 inhibitors is considered
to be a major step forward in treating painful
and inflammatory conditions such as RA and OA
with NSAIDs that are effective but with excellent
gastro-intestinal tolerability. While meloxicam
is a highly preferential COX-2 inhibitor, both
celecoxib and rofecoxib are the only NSAIDs to
be highly selective COX-2 inhibitors. These new
NSAIDs were introduced in India in 1998-2000.
standard protocols were designed for conducting
the first Indian RDB multicentric drug trials
comparing meloxicam, celecoxib and rofecoxib to
piroxicam and diclofenac in CRD, Pune, in patients
with RA and OA. Numerous individual trials, all
of 4 week duration, were held; over 650 patients
randomized. Besides Pune, patients were also recruited
in premier medical institutes in Delhi and Bombay.
After decoding, the entire patient data base was
statistically analyzed in CRD, Pune. Meloxicam,
celecoxib and rofecoxib were shown to be as effective
as piroxicam and diclofenac but much more safer;
similar to the World experience. Results were
presented in national meetings and submitted to
peer reviewed rheumatology journals.
An Ayurvedic (Asian Indian) drug for Rheumatoid
Arthritis (RA): Evaluation for Efficacy and Safety,
and a probable lipid modyfying effect
would be difficult, if not impossible, to validate
the entire Ayurvedic system on an ‘evidence
based medicine’ platform. But we, like several
other groups, believe that the promise and potential
of safety and efficacy of Ayurvedic medicines
is borne by their ancient use. However, bypassing
the conventional early stages of modern medicine
model of drug development, Ayurvedic medicines
could be directly tested for their clinical usefulness
in controlled clinical situations. Since several
years, our group has been validating anti-arthritic
formulations using standard clinical drug trial
protocols and GCP guidelines.
an Ayurvedic derived standardized antiarthritic
formulation, containing extracts of Boswellia
serrata (Salai Guggul),Trigonella foenum-graecum
(Fenugreek), Linum usitatissimum (Flaxseed), Camellia
sinensis (Greentea), Curcuma longa (Turmeric),
Tribulus terrestris (Gokharu), and Piper nigrum
( Black pepper) was evaluated in patients with
active rheumatoid arthritis (RA) for a period
of one year. This was a randomized, double blind,
placebo controlled, parallel efficacy study of
3 months followed by an open label phase.
demonstrated fair clinical efficacy with excellent
safety profile, and with significant lipid lowering
effect. The results were presented in the EULAR
(European league of rheumatology associations)
meeting in Berlin, 2004.
|| Title: NMITLI (New Millennium
Indian Technology Leadership Initiative) Arthritis
the auspices of Ministry of Science and Technology,
Government of India, the CSIR (Council Of Scientific
& Industrial Research) has launched a scheme
entitled NMITLI that seeks to realize the vision
of developed India in Science and Technology.
The scheme envisages to support innovation centered
scientific & technological developments as
a vehicle to attain for the country a global leadership
position at least in some selected niche areas.
Ayurveda is one such niche area that needs to
be developed in the modern context of evidence
based medicinal system.
primary focus in the NMITLI ARTHRITIS project
is to develop Ayurvedic herbal-based preparations
for treatment of osteoarthritis (OA) knees , with
special reference to pain relief, better quality
of life and chondroprotection. The project will
also explore early leads of these formulations
in patients with early rheumatoid arthritis (RA).
the ‘NMITLI ARTHRITIS’ project, it
is proposed to carry out numerous standard state-of-the-art
clinical drug trial driven evaluations for efficacy
and safety of pre selected Ayurvedic plant formulations
in patients with symptomatic OA knees.
research model envisages concurrent pharmacological
and clinical development to achieve quality-standardized
product, define mechanism of action, identify
active principles, document safety and demonstrate
clinically significant efficacy. The clinical
drug trial evaluations would begin along with
animal and other bench studies- a truly reverse
pharmacology paradigm fuelled by historical and
authoritative Ayurvedic knowledge of medicinal
use spanning thousands of years. However, clinical
and all other evaluations would be performed as
per state-of-the art protocols using modern medicine
science and concepts. Well designed and appropriately
powered scientific experiments and explorations,
and rigorous drug testing and clinical trials
will steer the development and progress step-wise
to ultimately finalize the final formulation of
the herbal medicine within a four year project
study is being carried out in KEM Hospital Mumbai,
Swami Prakashnanda Ayurved Research Center –Mumbai,
Nizam’s Institute of Medical Sciences- Hyderabad
and All India Institute of Medical Sciences- Delhi.
CRD, Pune is the Co-ordinating center for this
NMILTI project with Dr Chopra being the Principal
Investigator & the Clinical Co-ordinator.