Rationale
for study {6a}
The possibility of another COVID-19
wave in India (and other parts of the globe) can’t be entirely ruled out. This necessitates
generating evidence-base for population-based interventions which can improve
immune system functioning and reduce the susceptibility of infections in
vulnerable groups like pregnant women. Yoga can be practiced by pregnant women
as self-care with minimal training. However, there are no studies from India
which have assessed effect of Yoga-based intervention on immune function in
pregnant women.
Objectives
{7}
The overall
aim of this pilot randomized controlled trial is to examine the feasibility,
acceptability, and preliminary efficacy of aYoga-based intervention to improve
maternal mental health and immunity (YOGA-M2).
The primary
objectives of this randomized pilot trial are:
1. To
estimate patient eligibility, recruitment and retention-in-care and study
completion rates
2. To assess
the feasibility of delivering YOGA-M2and acceptability of this
intervention by the participants.
3. To assess
the preliminary efficacy of YOGA-M2to improve maternal mental health
andimmune function.
Trial
design {8}
Individual
randomized parallelgroup-controlled pilot trial with 1:1 allocation ratio.
Methods:
participants, interventions, and outcomes
Study
setting {9}
The study
will be carried out in four villages close to Pravara Institute of Medical
Sciences (PIMS)in Rahata taluka of Ahmednagar district in Maharashtra, India. Rahata
is one of the 14 administrative blocks (taluka) in Ahmednagar district with a
total population of 320,485 out of which 81.8% is rural(13). PIMS has a tertiary care center with
a 1275 bedded multi-disciplinary facility and is locatedin Loni Budruk village.
The antenatal clinic of the Department of Obstetrics and Gynecology provides services
to approximately150-200 pregnant women every day. This study will recruit
pregnant women from four neighboring villages: Loni Khurd, Loni Budruk, Kolhar
Budruk, and Kolhar-Bhagwatipur. The total population of these villages is 56,482(13).
Eligibility
criteria {10}
Pregnant
women attending the antenatal clinic of the Department of Obstetrics and
Gynecologywill be eligible to join the study. An eligibility assessment form will
be completed by a trainedResearch Assistant (RA)in the antenatal clinic after
they complete the clinical examination by their obstetrician. Following inclusion/exclusion
criteria will be used to assess the eligibility:
Inclusion
criteria:
-Adult
pregnant women above 18 years of age
-Gestational
age between 12-24 weeks
-Intending to
reside in the study area (described above) for the entire duration of the study
Exclusion
criteria:
-Pregnant
women advised rest by their obstetrician due to medical/obstetric problems
-History of
two or more spontaneous abortions
-Inability to
communicate in Marathi language
-Inability to
attend yoga sessions
-Receiving
treatment for depression or any other mental health condition
-Practicing
yoga regularly for at least once a week since last four weeks
Informed consent
{26a}
Eligible
participants will be invited to participate in the study, and they will be
given a participant information sheet which will provide a balanced written
account of the purpose and the design of the trial.The information sheet will
also include details of who to contact to ask any questions regarding the trial
design. An audio-visual version of this participant information sheet will be
uploaded on the website and
the participants will be informed about how to access this.
Eligible
participants who agree to participate in the study will provide written consent
by completing a hard copy of the consent form. They will have the opportunity
tocarefully review the written consent
form and ask questions regarding the study prior to signing the consent form.
Participants who are illiterate (not able to read and write Marathi, but can
communicate in Marathi), will provide a verbal consent (audio-recorded) after
the RA reads out the information sheet to them. An impartial third party (a
family member or a health care worker) will witness the consent process and will
sign the consent form.
A separate written informed consent will
also be obtained at 3-month follow-up assessment, for the qualitative sub-study
and for the audio/video recording of the yoga sessions to monitor fidelity and
quality of intervention delivery.
RAs will be trained to ensure that the purpose
of the study, randomization and other study procedures are adequately
explained, and the informed consent is appropriately obtained. They will be
required to sign the consent forms as well.
A copy of the participant information
sheet and the informed consent form will be left with the participants.Those
who decline to participate will be asked the reason for refusal and with their
permission, their age,education, occupation, and religion will be recorded.
Refusals at 3-month follow-up will also be recorded.
Additional
consent provisions for collection and use of participant data and biological specimens
{26b}
It
will ask the participants consent to share the anonymized data with other
researchers and to use the anonymized data to support other research in the
future.
Interventions
Intervention
arm: Yoga-based intervention for maternal Mental health and iMmunity
(Yoga-M2)
Participants
randomized to the intervention arm will attend weekly supervised group yoga
sessions and will also be requested to practice yoga regularly at home for a
total duration of three months. Group yoga session will be for 60 to 75
minutes. A typical session will begin with introduction of the participants, a
brief overview of the session by yoga instructor and an opening prayer. This
will be followed by sukshma-vyayam (micro-circulation exercises) for 10
minutes, asanas in standing, sitting, and supine position for 15 minutes,
pranayama for 15 minutes followed by shavasana (deep relaxation)
for 10 minutes. The session will end with a closing prayer. A detailed
description of yoga session is provided in table 1.After the session ends, yoga
instructor will spend time with each participant individually and suggest
changes/modifications based on any problems they might have in practicing any
of the yoga-based activities. Weekly group sessions will be conducted either in
facetoface or online format. Face to face sessions will be preferred if
allowed,depending on the COVID-19 pandemic-situation in the study area and
restrictions in-place. Face to face sessions will be in a well aerated and
ventilated hall. Use of sanitizers where appropriate and physical distancing
will be maintained during yoga sessions. Participants can also attend group
yoga sessions online via zoom platform.
In addition
to the weekly supervised group sessions, participants will be encouraged to
practice the yoga sequence at home daily for at least 30 minutes. Yoga
instructor will work with each participant and help them develop their home
practice schedule. A booklet containing the detailed description of each of the
included activity and a photograph of that activity will be provided to
participants. The contents of the booklet and the videos explaining the Yoga-M2
sequence will also be uploaded on the project website and participants will be
explained about how to access this material. A token amount will be paid to
each participant in the Yoga-M2 arm (INR 100 per session) to cover travel
expensesfor attending face-to-face yoga sessions. In case, the participant
attends via zoom then INR 50 per session will be paid to cover expenses related
to internet data use.Group yoga sessions will be facilitated by a certified and
experienced woman yoga instructor. During the sessions, she will provide
particular emphasis on, a) awareness of breath, b) focus on bodily sensations
during each of the yoga activities, and c) avoiding injuries due to yoga
practice.
In addition
to the yoga practice, participants will be provided educational leaflets (appendix
X) containing information about physical activity, sleep, and diet during
pregnancy.
Table 1: Yoga-based
intervention for maternal Mental health and iMmunity (Yoga-M2)
|
|
Type of
Activity
|
Duration
(Second
Trimester)
|
Duration
(Third
Trimester)
|
|
1.
|
Opening
Prayer
|
3
minutes
|
3
minutes
|
|
2.
|
Sukshma-Vyayam
(Micro-circulation
exercises)
|
10
minutes
|
5
minutes
|
|
|
Griva
Sanchalan
Neck
movements
|
Yes
|
Yes
|
|
|
Skandha Paribhraman
Shoulder
rotation
|
Yes
|
Yes
|
|
|
Hasta
Ayama Svasanam
(Hands in
and out breathing)
|
Yes
|
Yes
|
|
|
Hasta
Vistara Svasanam
(Hands
stretch breathing)
|
Yes
|
Yes
|
|
|
Gulpha
Vistara Svasanam
(Ankle
stretch breathing)
|
Yes
|
Yes
|
|
|
Karna
Sanchalan
Ear
movements
|
Yes
|
Yes
|
|
|
Skandha
Svasanam
Shoulder
movements
|
Yes
|
Yes
|
|
|
Parshva
Skandha Svasanam
Shoulder
cross movements
|
Yes
|
Yes
|
|
|
Hastottan
Svasanam
Arms over
head movements
|
Yes
|
Yes
|
|
|
Vyaghra
Svasanam
(Tiger
breathing)
|
Yes
|
No
|
|
|
Setu
Bandha Svasanam
(Bridge
posture breathing)
|
Yes
|
No
|
|
3.
|
Asana (Postures)
|
15
minutes
|
10
minutes
|
|
|
Standing
Asanas
|
|
|
|
|
Tadasana
(Tree pose)
|
Yes
|
Yes
|
|
|
Ardhakati
Chakrasan
(Lateral
arc pose)
|
Yes
|
Yes
|
|
|
Trikonasan
(Triangle
pose)
|
Yes
|
Yes
|
|
|
SittingAsanas
|
|
|
|
|
Vajrasana
(Ankle
pose)
|
Yes
|
Yes
|
|
|
Vakrasana
(Spine
twist pose)
|
Yes
|
No
|
|
|
Siddhasana
(Sage pose)
|
No
|
Yes
|
|
|
Baddhakonasana
(Bound
ankle pose)
|
No
|
Yes
|
|
|
Upavistakonasana
(Spread
legs pose)
|
No
|
Yes
|
|
|
Malasana
(Garland pose)
|
No
|
Yes
|
|
|
Supine Asanas
|
|
|
|
|
Viparita
Karani
(Half
shoulder stand)
|
Yes
|
No
|
|
|
Supta-baddha
Konasana
(Folded leg
lumbar stretch)
|
Yes
|
Yes
|
|
4.
|
Pranayama
and Meditation
|
10
minutes
|
20
minutes
|
|
|
Vibhagiya
Pranayam
Sectional
breathing
|
Yes
|
Yes
|
|
|
Anulom-Vilom
Pranayam
(Alternate
nostril breathing)
|
Yes
|
Yes
|
|
|
Sheetali
Pranayam
(Cooling
breath)
|
Yes
|
Yes
|
|
|
Bharamari
(Humming
breath)
|
Yes
|
Yes
|
|
|
Nadanusandhana
(Mind-sound
resonance)
|
Yes
|
Yes
|
|
5.
|
Dirgha
Vishranti Paddhati
Deep
Relaxation Technique
|
10
minutes
|
15
minutes
|
|
6.
|
Closing
Prayer
|
2 minutes
|
2 minutes
|
|
|
Total
Duration
|
50
minutes
|
55
minutes
|
Yoga-M2
is based on the Integrated Approach for Yoga Therapy during pregnancy (IAYT-P)(14).This intervention was earlier
evaluated using a randomized controlled trial design in an urban population in
Southern India. The participants were recruited froma hospital in Bengaluru
city and 96 women in 20th week of normal pregnancy were randomizedto either
IAYT-P group (n=51) or control group (n=45). Participants in control group did
standardantenatal exercises, one hour daily, from 20th to 36th week of
gestation. They found thatPregnancy relatedExperience (PEQ) reduced in Yoga
group by 26.86%, State anxiety decreasedby 15.65% in Yoga group while it
increased by 13.76% in control group and depression decreased30.67% in Yoga
group and increased 3.57% in control group(14).
Adaptations
to IAYT-P were essential to include activities to improve immune function and tailor
the delivery of the intervention for a rural context affected by COVID-19
crisis. This was done by reviewing the literature,undertaking a qualitative
study with pregnant women and community health workers, and conducting an
intervention adaptation workshop with pregnant women. Table 2 provides the summaryof
the intervention adaption process.
Table 2:
Intervention adaptation process
|
Method
|
Description
|
Changes
made to IAYT-P
|
|
Literature
review
|
·
Interventions
usedin previous studies (included in systematic review by Falkenberg et.al.,(11)) assessing the effect of yoga on
immune function were reviewed in detail.
·
A
book titled, ‘Yoga as Medicine: The Yogic Prescription for Health and Healing,’
by Dr. Timothy McCall (15)was referred.
·
Yoga
manual for pregnant women developed by the Morarji Desai National Institute
for Yoga (MDNIY)(16)was referred.
|
·
Neck
movements included in the manual by MDNIY were added.
·
Shoulder
movements were added as they likely improve the flow of lymph (15).
·
Advice
on diet, sleep hygiene and physical activity was added.
|
|
Qualitative
Study
|
·
10
In-depth interviews with pregnant women to explore facilitators and barriers
to yoga practice
·
3
Focus group discussions with community health workers to assess the
feasibility of conducting group sessions in the community settings.
|
·
Community
hall or anganwadi center to deliver group yoga sessions instead of a
hospital setup as pregnant women preferred a location close to their homes.
·
Modifications
in a few asanas as some pregnant women will be able to attend the
sessionswearing saree (a long piece of cloth draped around the body
and over one shoulder, worn by women in India).
·
Recruitment
of participants in the antenatal clinical of PIMS, as the community health
workers suggested that treating obstetrician should approve the practice of
yoga by pregnant women.
|
|
Intervention
Adaptation Workshop
|
·
Two
intervention adaptation workshops; one with four pregnant women and other
with three pregnant women were conducted to get their feedback on the
modified yoga sequence.
|
·
No
changes were made in the modified sequence as all the participants provided positive
feedback on the modified yoga sequence.
|
Comparison
arm: Enhanced Usual Care (EUC)
Participants
randomized to the EUC arm will receive a single session of health education
delivered by the IC. During this session, aspects related to sleep hygiene and
diet during pregnancy will be discussed and they will be encouraged to
undertake regular physical activity (150 min/week). They will be provided educational
leaflets (appendix X) containing information about physical activity, sleep,
and diet during pregnancy.IC will work with the participant to identify ways to
reduce stress during pregnancy and improve social support. As per the
current standard of care in the antenatal clinic of Department of Obstetrics,
pregnantwomen are neither screened for stress nor there is any discussion about
improving mental health during pregnancy. Participants with moderate stress
(Perceived Stress Scale score > 14) will be referred to a psychiatrist in
PIMS.
Criteria
for discontinuing or modifying allocated interventions {11b}
There are no
specific criteria for discontinuing or modifying allocated interventions.
Participants may choose to stop doing the yoga programme themselves for any
reason or may be advised by their obstetrician to discontinue practice due to
health issues.
Strategies
to improve adherence to interventions {11c}
Intervention
Coordinator and yoga instructor will regularly contact participants in Yoga-M2
arm to coordinate attendance in weekly group yoga sessions. If a participant
misses two consecutive weekly group yoga sessions, IC will visit the
participant at home to address any barriers related to joining the session.
Adherence to home practice will be assessed using home practice logs.
Relevant
concomitant care permitted or prohibited during the trial {11d}
Usual care
for participants continues throughout thetrial. There is nothing prohibited.
Provisions
for post-trial care {30}
Towards the
end of three months, participants in Yoga-M2 arm will receive
details of other suitable yoga classes that they could join on a self-pay
basis. The control participants will receive the same information after
completing the follow-up assessment. There are no specialcompensation
arrangements for those who suffer non-negligent harm fromtrial participation.
Outcomes
{12}
Outcome
assessment will include measures related to:
a) feasibility
and acceptability of yoga-based intervention delivery
b)
preliminary efficacy of yoga-based intervention
Feasibility and
acceptability will be assessed using the following process data:
1. Number and
proportion of eligible participants who are recruited per week in each arm
2. Number and
proportion of recruitedparticipants in the intervention arm who attend the
face-to-face yoga sessions.
3. Number and
proportion of recruitedparticipants in the intervention arm who attendat least 50%
of the follow-up yoga sessions.
4. Number and
proportion of recruited participants who complete follow-up assessment three months
post-randomization in each arm Table 3:
Measures to assess the preliminary efficacy
|
Outcome
|
Measure
|
Time-point
|
|
Stress
|
Perceived
Stress Scale (PSS)
|
Baseline
and 3-months post-randomization
|
|
Quality of
Life
|
EuroQoL 5
Dimensions Score (EQ-5D-5L)
|
Baseline
and 3-months post-randomization
|
|
Immune
Function
|
Wisconsin
Upper Respiratory Symptom Severity Scale
|
Baseline
and 3-months post-randomization
|
|
Immune
Function
|
Serum
C-Reactive Protein
|
Baseline
and 3-months post-randomization
|
|
Injuries
due to yoga
|
Self-report
log
|
Every week
for 3-months post-randomization
|
|
Serious
Adverse Events (SAE)
|
SAE report
form
|
Baseline
and 3-months post-randomization
|
Perceived
Stress Scale (PSS) A 10-item
version of PSS (17)will be used to measure perceived
stress. The items in this instrument assess how unpredictable, uncontrollable,
and overloaded participants appraise the situations in their lives in last one
month.PSS has been widely used in research studies across the globe and it has acceptable
psychometric properties (18). In this study, we will use the
Marathi version of the PSS which was translated from the English version using the
WHO guidelines for process of translation and adaption of instruments (19).
EuroQoL 5
Dimensions Score (EQ-5D-5L) Health
related Quality of Life (HRQoL) will be measured using European Qualityof Life
Five Dimension (EQ-5D-5L) descriptive system. This is a health utility instrument,
and it includes following fivedimensions: mobility, self-care,usual activities,
pain/discomfort and anxiey/depression. A single utility score will be
calculated using the value set/preference weights for Thailand as the Eq-5D
value set for India is under development (20). Participants will also provide an
overall evaluation of their health using a visual analogue scale (VAS). The
score on the scale ranges from 100 (best imaginable health) to 0 (worst
imaginablehealth).We will use the Marathi version of EQ-5D-5L with permission
from the EuroQoL Group(21).The EQ-5D has been validated in many
differentpatient populations(22). Wisconsin
Upper Respiratory Symptom Severity Scale (WURSS) The incidence
and severity of upper respiratory tract infections in the participants will be
assessed using the Wisconsin Upper Respiratory Symptom Survey (WURSS).The
construct validity of the WURSS has been supported by measures of reliability,
responsiveness, importance to patients, and convergence (23). The WURSS-21 includes 10 items
assessing symptoms, nine items assessing functional impairments, and one item
assessing global severity and global change. Participants will complete the
one-page WURSS-21 at the end of each day in the study.We will use the Marathi
version of WURSS with permission from the developers. Serum
C-Reactive Protein (CRP)
CRP has been proposed as an objective marker to
measure wellness (24). CRP is a nonspecific maker of inflammatory process,
the serum levels increase with body insult, tissue damage, aging, and
cardiovascular diseases. Bacterial (or viral, fungal) infections lead to a
marked increase in serum CRP levels. Although it is not a diagnostic marker, it
can be used to track the inflammatory process, overall wellness, and individual’s
quality of life. Lifestyle changes such as cessation of smoking, increasing
physical activity, reducing body mass index led to decrease in serum CRP levels(24).Yoga and other mind-body techniques reduce
inflammation through reduction in CRP (25).Two randomized trials conducted with heart
failure patients found that an 8-week Hatha yoga program led to significant
reductions in serum concentrations of IL-6 and CRP relative to standard
medical treatment (26,27) |
