Effect of Yoga therapy on Autonomic Functions in Multiple Sclerosis: A Randomized Controlled Trial

The present study is a randomised controlled trial to assess the effect of add-on yoga therapy on autonomic functions in patients diagnosed with multiple sclerosis. There is an increased risk of cardiovascular events in MS [Rzepiski et al., 2022] and CAD has been correlated with the pathophysiological processes of this disease. This causes an increase in the mortality rate of MS patients as compared to general population [Findling et al., 2020]. Continuous monitoring of HRV which is a non-invasive measure used to assess the activity of the ANS [Studer et al., 2017] has disclosed a strong relationship between CAD and the severity of MS [Hilty et al., 2022]. Identifying CAD in MS is of critical importance as in previous research cardiac sympathetic reactivity has been found to be an independent predictor of recovery in such patients [Studer et al., 2017]. Autonomic dysfunction including CAD, can also serve as an independent predictor for the development of the next relapse after a clinically isolated syndrome CIS [Findling et al., 2020]. Yoga helps in regulating cardiac autonomic activity by increasing HRV and vagal dominance [Tyagi Cohen, 2016]. An improved HRV is a sign of a healthy heart [Thayer et al., 2012]. Previous studies suggest that yoga practices directly stimulates vagus nerve and boosts parasympathetic output [Innes, Bourguignon Taylor, 2005]. Whereas, parasympathetic dominance leads to improved cardiac function, mood, energy states and strengthened neuroendocrine, metabolic, cognitive, and immune responses [Thayer et al., 2012] [Porges, 2011]. Further, the yoga interventions used in the previous studies have been heterogenous. In the present study, we will be using a validated yoga module [Varambally et al., 2021] [Palukuru et al., 2021]. The previous studies that have explored the effects of yoga on MS did not assess the extent to which the subjects were able to learn and perform practices. Thereby, yoga performance assessment [YPA] that is included in this study will help us understand the effects of the quality of the yoga practice on the symptoms of MS. The frequency of yoga sessions per week in most of the previous studies has been one to three sessions per week [Abasyank et al., 2021] [Dunne et al., 2021] [Guner Inanici, 2015] [Najafi Moghadasi, 2017] with very few exceptions [Pan et al., 2022] [Karbandi et al., 2015]. A systematic review assessing the effect of yoga on inflammatory biomarkers including 15 studies has reported that a higher dose of yoga results in greater improvements in inflammation [Djalilova et al., 2019]. A positive dose-response relationship has been previously discussed in many studies, including yoga for restless leg syndrome [Innes et al., 2020] and yoga for Major Depressive Disorder [MDD] [Streeter et al., 2017]. Another systematic review and meta-analysis published in 2018 assessing the effects of Mind–Body Exercises Yoga/Tai chi on HRV Parameters including 17 studies found robust evidence of yoga to be more effective in improving HRV than other mind-body practices. This meta-analysis further elaborates that studies which showed significant results of the Yoga intervention reported a total weekly training volume of 60 to 200 minutes/week, training frequency of 1 to 2 times/week and total intervention duration of 8 to 16 weeks [Zou et al., 2018]. The present study will be offering yoga sessions- one hour per day, 5 sessions per week for a period of 24 weeks. This is being done to understand the effect of high intensity yoga intervention on autonomic functions in MS patients.

METHODOLOGY

HYPOTHESIS NULL HYPOTHESIS

-Add-on yoga intervention for MS will have no effects on heart rate variability HRV in patients with MS.

-Add-on yoga intervention for MS will have no effects on Ewing battery scores in patients with MS.

-Add-on yoga intervention for MS will have no effects on depression, anxiety and Quality of Life QOL in patients with MS.

-Add-on yoga intervention for MS will have no effects on autonomic function scores in patients with MS.

-Add-on yoga intervention for MS will have no effects on fatigue, pain and disability scores in patients with MS.

-Add-on yoga intervention for MS will have no effects on the level of anti-inflammatory markers namely, IL-10 and the level of pro-inflammatory levels in patients namely, TNF-, IL-6 and IL-12p40 in patients with MS.

-Add-on yoga intervention for MS will have no effect on the number and frequency of relapses in patients with MS.

ALTERNATE HYPOTHESIS

-Add-on yoga intervention for MS will improve heart rate variability in patients with MS.

-Add-on yoga intervention for MS will improve Ewing battery scores in patients with MS.

-Add-on yoga intervention for MS will improve depression, anxiety and QOL in patients with MS.

-Add-on yoga intervention for MS will improve autonomic functions scores in patients with MS.

-Add-on yoga intervention for MS will improve fatigue, pain and disability scores in patients with MS.

-Add-on yoga intervention for MS will increase the level of anti-inflammatory markers namely, IL-10 and decrease the level of pro-inflammatory levels in patients namely, TNF-, IL-6 and IL-12p40 in patients with MS.

-Add-on yoga intervention for MS will improve the number and frequency of relapses in patients with MS.

STUDY DESIGN

Design: Assessor Blinded Randomized Controlled Trial

Number of groups will be 2

Consecutive consenting eligible subjects with MS will be randomly assigned to any one of the 2 groups 1 is to 1 allocation ratio, using computer-generated random numbers

1]Intervention group [Direct +  Tele-Yoga and Standard care] YG

2]Control group [Direct + Tele- Physiotherapy and Standard care] CG.

Sample size 80 [40 each in the Experimental group and Control group]

Sampling: Convenient sampling.

SAMPLE SIZE ESTIMATION

The sample size for moderate effect size change over 24 weeks intervention with 2 measurement times as HRV data will be recorded at baseline and then at the end of the 24th week and two groups f [0.18] with an alpha of 0.05, powered at 0.80 using GPower 3.1 Program [Zou et al., 2018] was 64. The sample size was calculated based on the HRV normalized high frequency values. Considering a 25 per cent attrition rate, the sample size becomes 80 Total Sample size 80 [40 subjects in each group]

INTERVENTION EXPERIMENTAL GROUP Yoga Group [Direct-Yoga and Tele-Yoga]

The experimental group will be given a yoga module specifically targeting the MS symptoms in addition to the standard care he/she is receiving.

-The first two sessions will be direct at the NIMHANS Integrated Centre for Yoga, Department of Integrative Medicine, NIMHANS.

-This will be followed by live direct and tele-yoga sessions of the same yoga module.

Dose of yoga intervention including live supervised direct and tele-yoga sessions will be offered five days/ week for 24 weeks [Total 120 sessions].

In addition, the subjects will continue to take the medication prescribed by the treating neurologist.

CONTROL GROUP

The control group will be given Physiotherapy exercises in addition to the standard care he/she is receiving. The Physiotherapy module has been developed under the guidance of a Senior Physiotherapist from Physiotherapy Centre, NIMHANS.

-The first two sessions will be direct at the NIMHANS Integrated Centre for Yoga, Department of Integrative Medicine, NIMHANS.

-This will be followed by live direct and tele-physiotherapy yoga sessions.

Dose of Physiotherapy intervention including live supervised direct and tele-Physiotherapy sessions will be offered five days/ week for 24 weeks [Total 120 sessions].

In addition, the subjects will continue to take the medication prescribed by the treating neurologist.