Lifestyle modifications, dietary changes and yoga versus conventional treatment for Constipation predominant Irritable Bowel Syndrome - a randomized controlled trial

Lifestyle modifications, dietary changes and yoga versus conventional treatment for Constipation predominant Irritable Bowel Syndrome - a randomized controlled trial

Background of study

Irritable Bowel Syndrome (IBS) is the commonest functional gastrointestinal disease seen by gastroenterologists in day to day clinical practice. About 50-90% of IBS patients who seek medical advice have concomitant psychiatric disorders.One third of the patients diagnosed to have IBS usually have anxiety and depression which often goes unnoticed despite a meticulous history.IBS patients miss three times as many days from work as do those without bowel symptoms due to ill health and have an overall poorer quality of life (QOL).The economic burden of IBS in the United States is estimated to be 30 billion $ annually.Treatment of IBS is essentially symptomatic and comprises of pharmacologic and psychological approaches. Educating patients is as much a physician’s duty, as receiving education is a patient’s right. Many patients do not comply with advice on follow up out-patient visits and prolonged medications despite substantial benefit associated with such follow-up care. Motivation, lifestyle modifications, education and support are the key to the successful management of IBS. There is a need for appropriate lifestyle modifications for better management of disease. Despite this, very few studies appear to address the communication needs of patients with IBS and its impact on disease outcomes. This study is aimed to overcome the knowledge gap for lifestyle modifications in IBS.

Objectives

·         To evaluate the effect of Lifestyle modifications dietary changes and yoga versus conventional treatment for the management of Irritable Bowel Syndrome

·         To study the effect on these on Quality of life (QOL), compliance to therapy, anxiety and depression

 METHODS

We will be prospectively including patients aged 18 to 70 years (both inclusive) of either sex with a definite diagnosis of IBS meeting Rome IV criteria and its subtypes who visit the outpatient clinic of the All India Institute of Medical Sciences (AIIMS), New Delhi from March 2018 till September 2020.

Inclusion criteria:

a)      18-70 years of age

b)      Symptom duration as per Rome IV criteria

Rome IV Criteria for Diagnosing IBS#

Recurrent abdominal pain, on average, at least 1 day/week in the last 3 months, associated with two or more of the following criteria:

·         Related to defecation

·         Associated with a change in frequency of stool

·         Associated with a change in form (appearance) of stool

#Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis

IBS-C - hard or lumpy stools at least 25% of the time, and loose or watery stools less than 25% of the time

Exclusion criteria

Patients are excluded if they have one or more of the following conditions:

a)      Co-morbid illness :  IHD, CKD, cirrhosis of liver, severe respiratory illness, diabetes mellitus, and COPD

b)      Predominant diarrhea (IBS-D), a combination of the two (IBS-M, or “mixedâ€), or undefined (IBS-U)

c)      Current use of psychiatric medication or in the previous 6 months, pregnant or lactating women, patients with malignancy, unconfirmed diagnosis

d)     Patients denying to follow the lifestyle modification protocol and give informed consent

Study design: Randomised Controlled study

Study intervention

The included patients in each arm will be randomized into 2 groups

1. Lifestyle modifications (intervention) (Dietary changes + Yoga therapy)
2. Usual care will receive conventional treatment

                                                                                                  Lifestyle modifications for Irritable Bowel Syndrome

After waking up Pomegranate peel Tea

Cut pomegranate into 8 pieces and put it in a mixer add 100 ml water and run it for 2 minutes. Once juice is formed, filter it to get one glass of pomegranate juice (200ml). To this add one teaspoon of rock salt. Mix well and consume every morning for 2 months on empty stomach.

Oral cleaning: Natural products like salt and mustard oil, triphala churnam, neem stick, meswak stick need to be used. Other toothpaste need to be avoided

Physical activity: 30 min of routine physical activity, walking or yoga as appropriate

Two meal diet plan: Preferably before or around 9am and 6pm evening

*curry leaf powder + ghee in first morsel of food

15 gms/day ghee, Curry leaf powder 8gms/day (Approximately 450g of ghee per month need to be consumed).

Preparation needs the following ingredients

Curry leaves (kadipatta) (2 cups), Split chickpeas (Chana dal) (2 tbsp), Black gram (urad dal) (2 tbsp), Cumin seeds (jeera) (1 tbsp), Coriander seeds (sabut dhania) (1 tbsp), Dry red chillies (sabut lal mirch) (5 to 6), Tamarind (imli) (lemon-sized ball), Salt (to taste) and Oil (1 tbsp).

Method

Wash kadipatta and then let them dry off. Meanwhile in a kadhai, keep roasting the chana dal and the urad dal on medium heat till they have turned red. Then, take them off the heat and keep aside. Next, dry-roast the jeera and dhania on medium heat till they have turned brown in colour. Remove from the pan and keep aside. In the same kadhai, sprinkle a little oil and keep frying the sabut lal mirch for a few seconds. Keep aside. Now, pour in a tbsp of oil, add in the kadipatta and keep tossing them till they have roasted and have turned crisp. Turn off the heat and let all the roasted ingredients cool. Once they have cooled, grind the dals first, followed by the dhania, jeera and lal mirch. Next, add in the tamarind ball and grind again. Remove and keep aside. Then, separately grind the kadipatta into a fine powder. Mix up all the ingredients and store in an air-tight container. Curry leaf powder can be mixed with white steamed rice and ghee.

Important points

➢      The meal should be heavy and filling. It is recommended to have the first meal between 2-3 hrs after sunrise and second meal before sunset. Both the meals should be balanced with the traditional dishes

➢      Every bite should be chewed properly. It should get mixed well with saliva

➢      While eating no intermediate water sipping is encouraged, unless necessary

➢      Don’t club cooked and uncooked food together with the meal

In between the meals

➢      Any number of fruit servings can be taken

➢      Buttermilk and fruit juices without sugar can be consumed

➢      Best to avoid coffee and tea. If the craving is uncontrollable then replace with black tea or black coffee

➢      A minimum of 4 litres water must be taken every day. Water is to be sipped and held in the mouth for a while before gulping in.

Hot water: drink one glass of hot water before going to sleep at night

Vegetarian diet – No dietary restrictions

Nonvegetarian diet – No dietary restrictions

Fruits and vegetables – No restrictions

Buttermilk/ Curd should be taken compulsorily

2. Yoga intervention Integrated Yoga Module for IBS (IYIBS) (30 minutes of yoga to be practiced daily for a period of 2 months.  Structured yoga sessions will be given to patients in the form of video assisted patient education as well carry home patient information brochure and encouraged to practice daily at home).

Patients assigned to the yoga intervention, will do physical postures and pranayama (controlled breathing). The physical postures consist of preliminary stretching exercises followed by breathing exercises and then by asana. Participants will be instructed to follow a specific breathing pattern during each asana and asked to hold each pose in its final position for 10 to 30 seconds without holding the breath. The module will be tailored according to patient’s conditions. Participants will be encouraged to assess their own limits and hold the pose for less time, if necessary. The yoga asana will be practiced with awareness focused primarily on their physical movements and respiration. Each posture will be followed by an appropriate relaxation posture for 30 seconds to one minute. The session will conclude with relaxation (shavasana). Patients will be handed a pre-planned curriculum that will be progressively more challenging and which will facilitate adherence and secure repeatability of the intervention.

Asanas (Total ~ 5-minute session)

1.      Vajrasana 2 minutes

2.      Agnisar Kriya 2 minutes

3.      Shavasana 1 minute

Breathing techniques (Pranayama, total ~ 25-minute session)

1.      Forceful exhalation (KapÄlabhÄti; 4 minutes)

2.      Bhastrika Pranayama (4 minutes)

3.      Alternate nostril breathing (NÄdisuddhi; 108 times in 13 minutes)

4.      Right nostril breathing (Surya Anuloma Viloma; 4 minutes)

 Written informed consent will be obtained from all patients prior to study entry. IBS will be diagnosed based on typical history, absence of physical signs and investigations negative for organic causes. All patients will undergo a physical examination and routine blood testing including complete blood picture, C-reactive protein, erythrocyte sedimentation rate, blood glucose levels, albumin, creatinine, stool examination and flexible sigmoidoscopy or colonoscopy as decided by the treating physician. Rest of the investigations will be decided on a case to case basis. After screening the patients will be randomized to interventional and usual care groups. Intervention group will receive advice on lifestyle modification while usual care group will receive the standard of care. Patient information sheet will be provided for patients’ enquiries before entering the study. The study will be conducted in compliance with Declaration of Helsinki and ICH-GCP guidelines.

Study end point will be at the end of 4 months to look for absence of IBS symptoms

Management (Conventional treatment)

Evaluation and management will be based on standard guidelines. Soluble fibers and antispasmodics will be used when appropriate. Probiotics in selected set of patients who complain of bloating and flatulence. Anti-depressant, SSRI will be preferred in IBS C. Antidiabetic and hypertensive medicines will be used in those who have these premorbidities.

Treatment outcome

A 50% reduction in the predominant or target symptom (abdominal pain/abdominal distension/abnormal bowel habit) along with a similar improvement in subjective wellbeing will be used as clinically useful index of outcome. Stool consistency will be assessed on the basis of patient-reported symptoms with the Bristol Stool Form (BSF). Patients will be asked to use a Visual analogue scale (VAS) scale to rate their worst abdominal pain over the past 24 h on a daily basis (using a diary). Improvements in abdominal pain of at least 30% compared to baseline will be considered as clinically meaningful changes. The stool consistency entry criterion for IBS-C patients has been proposed to be a BSF score of 1 or 2. An improvement of ≥1 in the weekly BSF average will be used as the threshold for identifying a responder in IBS-C patients. The stool frequency entry criterion for IBS-C patients may be defined as less than 3 weekly complete spontaneous bowel movements (CSBMs). An increase of 1 CSBM per week compared to baseline is proposed as a clinically meaningful improvement in IBS-C patients.

IBS-Adequate Relief (IBS-AR) is easy to administer, easy to understand and asks the following question, “In the last 7 days, have you had adequate relief of your IBS symptoms?â€

IBS symptom severity scale (IBS-SSS)

The IBS-SSS is a 5-question survey that asks the severity of abdominal pain, frequency of abdominal pain, severity of abdominal distention, dissatisfaction with bowel habits, and interference with quality of life over the past 10 days. Subjects respond to each question on a 100-point visual analogue scale. Scores on the IBS-SSS can range from 0 to 500 with higher scores indicating more severe symptoms. Subjects can be categorized as having mild (75-175), moderate (175-300), or severe (>300) IBS. A decrease of 50 points is associated with a clinically meaningful improvement.

Adverse events

Adverse events classified by type, seriousness, severity, and relationship will be assessed in both groups.

Treatment failures

IBS will be considered refractory or intractable if patients have “not responded to any therapy†i.e., “not responded to standard medical treatment†or “no improvement to lifestyle and dietary modifications at 3 weeksâ€. We propose IBS be considered “treatment resistant†if: symptoms are present for >3 weeks; absence of response to an adequate dose of at least one pharmacological agent tried for a minimum of 3 weeks.

Indicators of treatment failure: switch/addition of constipation therapy, IBS-C related inpatient/emergency admission, fecal impaction, constipation-related surgery/procedure, or aggressive prescription treatments.

Questionnaires

Patients will be completing above mentioned questionnaires which will be administered at baseline, 4 weeks and at the end of 2 months of follow up period. Patients will be interviewed for compliance with medication, and in usual care group with lifestyle modification advised. Compliance to drugs, defined as drug intake of ≥ 80% of the prescribed dose, recall-period will be past two weeks.Anxiety and depression will be assessed by Beck inventory.No copyrighted questionnaire will be used.

Assessment interval

Clinical All patient details will be entered into a specially designed proforma and shall be kept confidential. Patient information will be kept anonymous and will be identified by their study numbers to maintain confidentiality. Patients will be assessed clinically at baseline, 4 weeks and at the end of 2 months. Patients will be given a symptom diary at the beginning of the study in which they will be asked to record their clinical symptoms every month and prior to 1 week of the final scheduled visit to hospital.

Direct access to source data/documents The investigator/institution will permit trial-related monitoring, audits, institutional review board/independent ethics committee review, and regulatory inspection(s), by the funding agency providing direct access to source data/documents. Only the research staff and investigators/co investigators will be accessing the source data and documents related to the research study. All of which shall be kept confidential. Subjects’ information will be kept anonymous. They will be identified by their study numbers to maintain subjects’ confidentiality. An independent staff will perform source data verification (a comparison of the data in the CRFs with the subject’s medical records at the hospital or practice, and other records relevant to the study).

Ethics Ethical approval will be sought from the Institutional Ethical Committee (IEC). Work related to this project will start only after clearance from IEC. Proposal shall be submitted to CTRI as well.

Data handling Patient data will be collected and recorded in the case report form after obtaining patient voluntary consent for participation. All forms shall be completed by the research team, checked for inaccuracies in the presence of investigator/ co investigators.

Record keeping Data will be stored for a period of 3 years from the completion of the study. Data can be shared with funding agency at request. All details shall be kept confidential. Only research staff will have access to the data which will be stored in the clinical research room. Research staff will enter the data in the computer. Data shall be backed up in external hard drive. Same will be continued throughout the study and back up on a weekly basis to prevent data loss.

Statistical Analysis

Randomization Simple randomization will be followed, whereby patients with IBS will be randomized to lifestyle modification and yoga with conventional treatment or usual care group that will only receive conventional treatment. For sequence generation random numbers will be generated by computerized random number (The RAND corp. Inc). The randomization list and numbered packing of the intervention will be prepared by a person not involved in the study.

All descriptive and inferential statistics will be generated using the SPSS version 21 (IBM Corporation, NY, USA). Wherever appropriate number, percentage, mean and median will be given.  Homogeneity between the two groups at baseline will be analyzed using Pearson’s chi-square test / Fisher’s exact for categorical data and Student’s t-test for continuous variables. Statistical testing of differences between the two groups will be done by independent sample t-tests, within the two groups by Friedman two-way analysis of variance by ranks and proportion with chi square test. Statistical tests will be considered significant when the p-value result is < 0.05.

Sample size calculation

Since there is no study which has assessed these outcomes a pilot exploratory study will be conducted to recruit patients with IBS. Anticipating a dropout rate of 20% we plan to recruit 100 patients with 50 in each group.

Purpose of the study

The effect of Lifestyle modification and Yoga in IBS is currently unexplored.  Hence, by prospectively following up IBS patients for a period of two months we intend to assess its effect on QOL, compliance, anxiety and depression.

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