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CTRI Number  CTRI/2017/07/009132 [Registered on: 27/07/2017] Trial Registered Retrospectively
Last Modified On: 31/12/2018
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Yoga & Naturopathy 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   An experiment involving people with Rheumatoid arthritis (joint pain illness) to see the changes of illness level, involuntary action of heart and blood test to measure immune (protective) response by giving yoga 
Scientific Title of Study   Effect of yoga therapy on disease activity, cardiac autonomic functions and inflammatory markers in patients of Rheumatoid arthritis - A randomized control trial 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  G Selvakumar 
Designation  Ph D Scholar 
Affiliation  Jawaharlal Institute of Postgraduate Medical Education and Research JIPMER 
Address  Department of Physiology JIPMER academic center 1st floor JIPMER campus Gorimedu

Pondicherry
PONDICHERRY
605006
India 
Phone  7094532785  
Fax    
Email  dr.selvaganesh@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr G S Gaur 
Designation  Professor and Head 
Affiliation  Jawaharlal Institute of Postgraduate Medical Education and Research JIPMER 
Address  Department of Physiology JIPMER academic center 1st floor JIPMER campus Gorimedu

Pondicherry
PONDICHERRY
605006
India 
Phone  9994470395  
Fax    
Email  drgsgaur@yahoo.com  
 
Details of Contact Person
Public Query
 
Name  G Selvakumar 
Designation  Ph D Scholar 
Affiliation  Jawaharlal Institute of Postgraduate Medical Education and Research JIPMER 
Address  Department of Physiology JIPMER academic center 1st floor JIPMER campus Gorimedu

Pondicherry
PONDICHERRY
605006
India 
Phone  7094532785  
Fax    
Email  dr.selvaganesh@gmail.com  
 
Source of Monetary or Material Support  
Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Dhanvantri Nagar Puducherry 605 006 
 
Primary Sponsor  
Name  Jawaharlal Institute of Postgraduate Medical Education and Research 
Address  Jawaharlal Institute of Postgraduate Medical Education and Research JIPMER Dhanvantri Nagar Puducherry 605006  
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 G S Gaur  awaharlal Institute of Postgraduate Medical Education and Research   Autonomic function test lab Room no 8123 Department of Physiology 1st floor JIPMER academic center block
Pondicherry
PONDICHERRY 
9994470395

drgsgaur@yahoo.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
JIPMER Institute Ethics Committee Human Studies  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  patients of Rheumatoid arthritis,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Standard medical treatment for Rheumatoid arthritis  All patients with rheumatoid arthritis (RA) attending the OP or IP services of the Department of Immunology after thorough clinical and laboratory investigations, they will receive methotrexate (unless contraindicated) as initial DMARD (Disease-Modifying Antirheumatic Drugs ) therapy 10 mg per week, escalated @ 5 mg / week, every 2 weeks up to a maximum of 25 mg per week or maximum tolerated dose whichever is less at the end of 6 weeks. Patients will receive NSAlDs (Diclofenac 50 mg twice a day and SOS basis for control of pain). Treatment response will be assessed using EULAR response criteria at the end of three months or after 6 continuous weeks of stable combination DMARD therapy whichever is later. 
Intervention  yoga therapy  Study group will undergo yoga therapy for 12 weeks (30 minutes, 3 times/week). Yoga therapy will be administered in the Department of ACYTER(Advanced Centre for Yoga Therapy Education and Research) by yoga instructors. Counselling will be given to control group. Both study group and control group will continue the standard medical treatment/drugs as prescribed by Department of Immunology. The attendance will be maintained for Yoga therapy sessions, regularity of home practice will be monitored by regular phone contact. (The schedule of Yoga therapy,Handouts, Video CD which contains the instructions of procedures will be given to the patients). YOGA THERAPY SCHEDULE 1. warming up : 2 minutes 2. Sukshmavyayama : 9 minutes a. Purna-bhuja- sakti-vikasaka(strengthening the arms) : 2 minutes b. Mani-bandha- sakti-vikasaka(strengthening the wrists) : 2 minutes c. Kara-tala- sakti-vikasaka(strengthening the palms) : 2 minutes d. Janu- sakti-vikasaka(strengthening the knees) : 1 minute e. Gulpha-pada-prstha-pada-tala- sakti-vikasaka (Developing the strength of the ankles and the feet) : 2 minutes 3. Yogasanas : 8 minutes Tadasana : 30 seconds Katichakrasana : 30 seconds Konasana : 30 seconds UrdhwaHastottanasana : 30 seconds Pavanamuktasana : 30 seconds Bhujangasana : 30 seconds Shavasana : 5 minutes 4. Pranayama : 6 minutes Nadishodhana Pranayama Chandrabhedi Pranayama Bhramari 5. Dhyana (meditation) : 5 minutes Total duration : 30 minutes  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  60.00 Year(s)
Gender  Both 
Details  1. Both genders between 18 and 60 years of age.
2. Newly onset Rheumatoid arthritis patients having disease duration less than 1 year with diagnosis of RA according to the 2010 ACR/EULAR criteria.
3. Rheumatoid arthritis patients partially responding to methotrexate therapy.
Details
All patients with rheumatoid arthritis (RA) attending the OP or IP services of the Department of Immunology after thorough clinical and laboratory investigations, they will receive methotrexate (unless contraindicated) as initial DMARD (Disease-Modifying Antirheumatic Drugs ) therapy 10 mg per week, escalated @ 5 mg / week, every 2 weeks up to a maximum of 25 mg per week or maximum tolerated dose whichever is less at the end of 6 weeks. Patients will receive NSAlDs (Diclofenac 50 mg twice a day and SOS basis for control of pain). Treatment response will be assessed using EULAR response criteria at the end of three months or after 6 continuous weeks of stable combination DMARD therapy whichever is later. Based on the treatment response patients will be classified as “good, moderate and poor responder”. Patients with complete response to methotrexate will continue the same medication. Whereas, those with poor response will be offered additional DMARD therapy (triple therapy). These two groups will not be recruited in the study. The patients labeled as ‘partial responders’ will be continued on methotrexate for a further period of 3 months. They will be enrolled in the study during this phase of stable methotrexate therapy.
 
 
ExclusionCriteria 
Details  1. Diabetes mellitus
2. Uncontrolled Hypertension (JNC 7 report)
3. Rheumatoid arthritis patients with apparent deformities.
4. Any other neuromuscular disorder.
5. Any other Auto immune disorders.
6. Patients who have undergone yoga therapy or any other bio-feedback techniques in last one year.
7. History of alcoholism or drug abuse within 1 year of screening.
8. Intra-articular steroid injections with in 4 weeks of screening. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
1.Disease activity scale-28

2.Biochemical & Immunological parameters
i) Inflammatory markers
1) ESR
2) IL-6
3) IL-1
4) TNF-α
ii) Oxidative stress markers
1) Serum malondialdehyde
2) Total antioxidant status
iii) adipokines – adiponectin,leptin
iv) serum cortisol (8.00 AM)
3. Cardiac autonomic function assessed by short term Heart Rate Variability.

4. BRS(Baroreflex sensitivity)
 
baseline and 12 weeks 
 
Secondary Outcome  
Outcome  TimePoints 
Quality of life by Health Assessment Questionnaire   baseline and 12 weeks 
 
Target Sample Size   Total Sample Size="150"
Sample Size from India="150" 
Final Enrollment numbers achieved (Total)= "183"
Final Enrollment numbers achieved (India)="183" 
Phase of Trial   N/A 
Date of First Enrollment (India)   10/08/2015 
Date of Study Completion (India) 18/12/2018 
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)
Modification(s)  
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  

1.Background :

 Rheumatoid arthritis (RA) is a chronic debilitating condition that affects 0.5 to 1 percent of the Indian population (1). RA is characterized by chronic joint inflammation, bony erosions, deformities, joint destruction, physical disability and is associated with significant morbidity, premature mortality and decline in the functional status of the patient (2). Major biological advances have been made in recent years, and aggressive pharmacologic treatment has resulted in patient improvements. However, not all patients respond effectively to treatment, and the use of some biological agents has been associated with medical risks and socioeconomic costs. Even when joint inflammation is medically controlled, some patients experience RA-related disability, suggesting the utility of complementary rehabilitation efforts, such as yoga.

A. Rationale :

RA is associated with altered body composition leading to reduction in fat-free mass, higher body fat content is present even in the underweight and normal weight RA patients.There is a higher incidence of centripetal obesity  in RA patients, without any obvious change in total body weight (3) In altered body composition, BMI may not be a valid predictor of Body fat .

Obesity is a chronic inflammatory condition and it independently associates with classical cardiovascular disease (CVD) risk factors in RA; RA patients are more likely to have such CVD risk factors.For a given Body Fat content, patients with RA have a significantly lower BMI, by almost 2 kg/m2 compared with the general population.If BMI cut-offs of 23 % and 28 % are taken for overweight and obesity similar to Asian-Indian population in whom body composition is also altered, prevalence of higher overweight (∼45%) and obesity (∼37%) occurs among RA patients(4).

Previous studies have reported adipokines like Leptin, adiponectin, visfatin and resistin, secreted from adipose tissue(5), are involved in the increased production of proinflammatory agents like TNF-α,  IL-1, IL-6 and CRP, which play important role in the pathogenesis of RA.Central adiposity is associated with insulin resistance and endothelial dysfunction in other  metabolic conditions like DM .Inspite of close associations of obesity both with CVD risk and inflammation, as well as the body composition changes observed in RA patients, there is paucity of data on the study of obesity and body composition in RA patients.

Incidence of CV mortality has been reported higher in RA than in general population. Previous studies report that conventional CVD risk factors do not fully explain excess CV morbidity and mortality in RA patients.In previous studies, cardiovascular autonomic dysfunction has been reported around 61–75% in RA patients(6). One previous study done in AIIMS reported overactivity of sympathetic nervous system and underactivity of parasympathetic nervous system in RA patients (7). The main pattern of dysfunction is impairment of cardiovascular reflexes and altered HRV, indicative of reduced cardiac parasympathetic (strong evidence) activity and elevated cardiac sympathetic activity (limited evidence). The literature up to date is underpowered to determine the causal relationships between inflammation, ANS dysfunction, & adiposity in RA.Other reports suggest that local inflammatory mediators like IL-1 and TNF-alpha upregulate expression of adhesion molecules in endothelial cells leading to endothelial dysfunction and leading to increase in CV atherosclerosis & CVD events(8).

Yoga is a mind body technique involving breath control, physical exercise and meditation. Beneficial in healthy subjects as well as in various diseases including auto immune disorders, rheumatoid arthritis and osteoarthritis. An RCT from the USA compared a 6-week Iyengar yoga intervention twice weekly with usual care. It  included 30 young women with RA. The RCT found no group differences in bodily pain on the SF-36 but Significant effects were reported for disability,pain(9). Another RCT originating from India included 80 patients with RA , yoga intervention given for 7 weeks compared with usual care, yoga significantly reduced pain on the (SDPIS) Simple Descriptive Pain Intensity Scale (10). Similarly few other small sized studies have reported that yoga therapy is beneficial on the hand grip strength, Quality of Life, pain scores, immune parameters like IL-6, depression and anxiety of rheumatoid arthritis patients (11,12,13). The evidence drawn from previous studies of yoga therpay on RA is still limited due to low methodological quality and outcome measures.

B.        Novelty :

There is paucity of data on the assessment and to find association, if any, between disease activity,  body composition, cardiac autonomic functions, inflammatory, and oxidative markers  in the patients of RA. Also, to the best of our knowledge, there is no previous study in which, effect of 12 weeks of yoga therapy has been studied in the RA patients. Therefore, present study has been conceived.

C.        Expected outcome & application :

 The expected outcome of the proposed study is the effect of 12 weeks of yoga therapy on disease activity, body composition, cardiac autonomic functions, inflammatory and oxidative markers in patients with  rheumatoid arthritis

Applicability

The outcome of the study will be highly useful for the treatment / management of  rheumatoid arthritis patients along with the standard medical treatment

3.         Research question(s) :

What is the effect of yoga on disease activity, body composition, cardiac autonomic functions and inflammatory and oxidative markers in patients with  rheumatoid arthritis ? 

4.         Research hypothesis (es), if any :

 Twelve weeks of yoga practice will reduce the disease activity, inflammation & oxidative stress and improve the body composition, cardiac autonomic functions in patients with  rheumatoid arthritis. 

5.         Aim and objectives:

Primary objective(s) :

1.     To assess the effect of 12 weeks of yoga therapy on disease activity, body composition, cardiac autonomic functions, inflammatory and oxidative markers in patients with  rheumatoid arthritis.

2.     To assess body composition, cardiac autonomic functions, inflammatory, oxidative markers and disease activity in patients with  rheumatoid arthritis.

3.     To identify the association of body composition, cardiac  autonomic functions, inflammatory, oxidative markers and disease activity among rheumatoid arthritis patients.

Secondary objective(s)

To assess the effect of yoga on quality of life by Health Assessment Questionnaire among  the patients with rheumatoid arthritis.

Relevant references for the project (in Vancouver style, cited sequentially in the text of project) :

 

  • 1.     Sokka T, Abelson B, Pincus T. Mortality in rheumatoid arthritis: 2008 update. Clin Exp Rheumatol  2008; 26(5): 35–61.
  • 2.     Mutru O, Laakso M, Isomaki H, Koota K. Ten year mortality and causes of death in patients with rheumatoid arthritis. Br Med J  1985; 290(6484): 1797-9.
  • 3.     Roubenoff R, Roubenoff RA, Ward LM, Holland SM, Hellman DB. Rheumatoid cachexia: depletion of lean body mass in rheumatoid arthritis: possible association with tumor necrosis factor. J Rheumatol 1992; 19: 1505–10.
  • 4.     Kremers HM, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Prognostic importance of low body mass index in relation to cardiovascular mortality in rheumatoid arthritis. Arthritis Rheum 2004; 50: 3450–7.
  • 5.     Hauner H. Secretory factors from human adipose tissue and their functional role. ProcNutrSoc 2005; 64: 163–9.
  • 6.     Stojanovich L, Milovanovich B , DeLuka SR, Popovich-Kuzmanovich D, Bisenich V, Djukanovich B et al. Cardiovascular autonomic dysfunction in systemic lupus, rheumatoid arthritis, primary Sjogren syndrome and other autoimmune diseases. Lupus 2007; 16: 181-5.
  • 7.     Yadav RK, Gupta R, Deepak KK. A pilot study on short term heart rate variability & its correlation with disease activity in Indian patients with rheumatoid arthritis. Indian J Med Res 2012; 136: 593–8.
  • 8.     Manzi S, Wasko MC. Inflammation-mediated rheumatic diseases and atherosclerosis. Ann Rheum Dis 2000; 59: 321–5.
  • 9.     Evans S, Moieni M, Lung K et al. Impact of Iyengar yoga on quality of life in young women with rheumatoid arthritis. Clin J Pain  2013; 29(11): 988-97.
  • 10.  Singh VK, Bhandari RB, Rana BB. Effect of yogic package on rheumatoid arthritis. Indian J Physiol Pharmacol 2011; 55: 329-35.
  • 11.  Williams K, Steinberg L, Petronis J. Therapeutic Application of Iyengar Yoga for Healing Chronic Low Back Pain. Int J Yoga 2003; 13: 55-67.
  • 12.  Balaji PA, Varne SR, Ali SS. Physiological effects of yogic practices and    transcendental meditation in health and disease. N Am J Med Sci  2012; 4: 442-8.
  • 13.  Badsha H, Chhabra V, Leibman C et al. The benefits of yoga for rheumatoid arthritis: results of a preliminary, structured 8-week program. Rheumatol Int  2009; 29: 1417-21.


 
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