Comparative Effectiveness of Panchamrut Parpati and Placebo in Management of Grahani W.S.R. to Irritable Bowel Syndrome - Study Protocol for a Single Blind, Randomized Controlled Trial

Abstract

Background: Ayurveda has described several treatment modalities regarding the treatment of Grahani Roga including the usage of herbs and formulations, yoga and lifestyle modifications. On the other hand, systematic data regarding their efficacy relative to placebo are not currently available. The purpose of this study is to compare the efficacy of the Ayurvedic formulation Panchamrut Parpati with a placebo, which contains an inert component called starch, in the treatment of Grahani Roga patients. Methods and design: In a prospective, single- centered, randomized controlled trial,60 patients, between 19 and 60 years, diagnosed with Grahani Roga, presenting with cardinal features of Grahani Roga as presented in Ayurvedic texts, two groups will be randomly assigned. In Group one, the patients will receive Panchamrut Parpati and in Group two, patients will receive Placebo filled with starch. Guidelines regarding Pathya-apathya will be given to both the groups. The course of treatment will last for 28 days for both groups. Outcomes will be evaluated on 14th&28th (During treatment) & 56th day (post-treatment). Result:The primary result will be assessed by checking the grading of the cardinal symptoms of Grahani Roga mentioned in Ayurvedic texts. Secondary outcome will check for improvement in laboratory investigations and quality of life of the patient. Conclusion: This trial compares the efficacy of Panchamrut Parpati with Placebo in the patients of Grahani roga. Panchamrut Parpati is envisioned to improve the symptoms of Grahani Roga, thus proving to be effective in management of patients of Grahani Roga. Trial registration: CTRI/2023/07/055048.

Introduction

I. BACKGROUND

In the present era, Grahani Roga is the prime disorder of the gastrointestinal tract because of its direct relation to improper dietary habits along with a sedentary and stressful lifestyle. In Ayurveda, Acharya Sushruta stated that Grahani is situated between Amashya & Pakwashya, and is known as the 6th Kala i.e.Pittadhara Kala.[1]Acharya Charaka considers Grahani as a site of Agni ( digestive enzymes) and normally it restrains the downward movement of undigested food and after digestion, it releases the food through the sides of its lumen. In abnormal conditions, it gets vitiated due to Agnimandhya and releases the food in undigested form only.[2]Grahaniroga manifests signs & symptoms like Muhurbadham Muhurdravyam mala pravriti (person voids stool in large quantity either in solid or liquid form)[3], Trishna (morbid thirst). Arochaka (anorexia), Vairasya (distaste in mouth), Praseka (excessive salivation) and Tamaka. The patient also suffers from Shunapadakara (edema in legs and hands), Asthiparvaruka (pain in bones and joints), Vomiting, Fever, Eructations having a metallic smell, the smell of ama and bitter along with sour tastes[4]. Based on all signs and symptoms Grahani roga is correlated with Irritable Bowel Syndrome. IBS is a gastrointestinal disorder characterized by altered bowel habits and abdominal pain in the absence of detectable structural abnormality. No clear diagnostic markers exist for IBS, all definitions of the disease are based on clinical presentation. In IBS biopsychosocial factors are also thought to play an important role along with luminal factors such as diet and gut microbiota.[5]

IBS affects around 11% of the population globally[6]. It most commonly occurs in young people, presenting before the age of 45 years. However, some reports suggest that the elderly are troubled by IBS symptoms up to 92 % as often as a middle-aged person. Young women are affected 2-3 times more often than men[7].

II. METHODS

A. Patients

1. Patients fulfilling the following criteria shall be included: Patients of either gender with the age group of 19-60 years presented with cardinal features of GrahaniRoga as described inAyurvedic texts, Randomly selected, who arewilling and able to participate in the study and provide written informed consent.
2. Patients are excluded for the following criteria: The patients below 19 years and above 60 years of age; who are suffering from Gastritis, intestinal obstructions, intestinal tuberculosis, ulcerative colitis, and other abdominal disorders; who are suffering from major systemic illnesses necessitating long-term drug treatment like Hyperthyroidism, Inflammatory bowel disease, Tuberculosis, Uncontrolled Diabetes, Hypertension, Psycho neuro-endocrinal disorders; Patients with concurrent serious hepatic/renal disorders, severe pulmonary dysfunction, or any type of malignancies; Patient on prolonged (>6 weeks) medication with corticosteroids, antidepressants, anticholinergics, etc.; Alcoholics and any other drug abusers; Pregnant and lactating women and The patient who has a history of Hypersensitivity to the trial drug or any of its ingredients.

The research has received approval from the Institutional Ethics committee vide no. SKAU/ Acad/2022/6758 ) and is carried out in compliance with the standard operating procedures for clinical trials (Declaration of Helsinki). The registration number for the trial is CTRI/2023/07/055048. Every patient gives their informed permission. The trial is currently in the hiring stage. The medication was purchased from a reputable pharmaceutical company that supplied quality control reports for two different medications.
B. Randomization

Patients are assigned at random to Groups A and B in a 1:1 ratio through a computer generated randomization sequence.

1. Study design:

Every patient participating in this prospective, single blinded, randomized controlled trial is given an Ayurvedic diagnosis prior to randomization.

Following randomization, patients in Group A, each Patient will be advised for taking Panchamrita Parpati (Capsule form) in the dose of 250 mg with Normal water twice daily for 28 days. Patients in Group B will be advised to take a Placebo (1 capsule) with normal water twice daily for 28 days. Contents of Panchamruta Parpati are listed below:

Table no: 1 - Contents of Panchamruta Parpati

Figure 1: Trial Design

2. Outcomes:

The principal result will be assessed by checking the grading of the cardinal symptoms of GrahaniRoga mentioned in Ayurvedic texts. Secondary outcome will check for improvement in lab investigations and quality of life of the patient. Results will be assessed on 14th& 28th (During treatment) & 56th day ( post-treatment ). The improvement in Grahani Roga's signs & symptoms mentioned in Ayurvedic texts will be used to evaluate the outcome. To establish the results statistically each sign & symptom will be given a specific score.

Table no 2: Assessment Criteria

C. Interventions

Group A - Each Patient will be advised for taking Panchamrita Parpati (Capsule form) in the dose of 250 mg with Normal water twice daily for 28 days.

Group B - Each Patient will be advised to take a Placebo (1 capsule) with normal water twice daily for 28 days.

Both Groups

In both groups Pathya-Apathya i.e. Specific diet (Ahara), and lifestyle modifications (Vihara) will be advised which is necessary for the management of Grahani Roga in every patient.

Statistics

The subjective parameters will be analyzed. The 30 patents in every group will be studied. Unpaired t-test will be applied on the collected data to achieve p value of 0.05.Detailed statistical plan will be developed before data analysis using SPSS and MS Excel.

III. DISCUSSION

In this trial, the efficacy of Panchamrut Parpati and Placebo in the treatment of Grahani is compared for the first time. IBS brings a very negative effect on the quality of life of a sufferer which is mostly underestimated by his/her family as well as co-workers. Patients face a lot of struggles in dealing with day-to-day activities. IBS has unpredictable symptoms, which are physically uncomfortable and very embarrassing for the patient. It decreases the patient's skills as he/she is not capable to concentrate on work with full energy because he/she is always surrounded by a sense of fear due to IBS symptoms. The patient shows less interest in social activities, can not plan any trips with friends, and even can't enjoy favorite meals. Sometimes due to bloating, gastric distention becomes a problem that not only affects the look of the person but also interferes with the person's choice of wearing clothes. The patient has to carry medication at every place. This hectic lifestyle has a very bad impact on the mental status of the patient which converts into many mental illnesses like anxiety, depression, stress, etc. All these things also affect one's relationship with a partner, relatives, and friends. Almost 10-15% population nowadays is suffering from IBS. As we know the exact cause of IBS is still not known in the allopathic medicine system and the treatment adopted is only symptomatic. The allopathic formulations may give instant relief for some time but have no permanent cure for the disease and may also have many adverse effects on the body. But the psychosomatic aspect of the diseases cannot be ignored. Also, IBS shows a significant placebo response of up to 40-50% in different clinical trials.[8] Placebo by acting at a psychological level helps to relieve symptoms up to much extent. In Ayurveda, IBS can be correlated with Grahani roga. Keeping in view of the above limitations and side effects this study has been chosen to fill this gap of providing a safe and effective line of treatment as Ayurveda provides multiple formulations for this. In Ayurveda Panchamrita Parpati mentioned in Bhaishjya Ratnawali[9] is advised to be given to the patients of Grahani roga. In Graghani roga the principal concern is the restoration of agni. In Ayurveda Parpati Kalpana is specifically indicated for the disorders of GI tract. The process of preparation of parpati is a sanskara provided through agni due to which it gains ushna guna and deepan properties[10] along with it is grahi in nature. There are various parpaties mentioned in Ayurvedic texts. But Panchamrut parpati is especially considered a drug of choice in the management of Grahani roga by Bhaisjya ratanawali[11] because Panchamruta parpati has Sudha Gandhaka, Sudha Parada, Loha bhasma, Abhraka bhasma, Tamra bhasma. Sudha Parada has Shada rasa, usna veerya, it is snigdha, sara and guru in Gunas[12]. Sudha Gandhaka is usna and agnikari[13]. Loha bhasma is rasayan and sarva vyadhi hara[14]. Abhraka bhasma is Trodoshashamaka.Vahnisandeepana[15]. Tamra bhasma is tikta kasaya in rasa, madhura in vipaka, usna in veerya[16]. Panchamrut parpati is a preparation made up of sanskar provided through agni. So after sanskar, it becomes rich in deepan pachana properties along with ushna guna which enhances the appetite. Panchamrut parpati is laghu, ruksha in guna, tikta in rasa, and ushna in veerya thus increasing the absorption of poshak rasa by opening the intestinal ducts as it penetrates up to minute srotas. By its guna and karmas it pacifies vata dosha thus convert the atiparvarti of mala into samyaka parvarti. Due to its deepan and grahi properties, it improves the absorption of nutritive substances and provides relief in associated symptoms like Pandu, svayathu, gulma, etc. In Bhaisajya ratnawali, Sangrahani rogadhikara it is said that Parpati is doshaghana, jantughana and balya for digestive system. It reduces the inflammation and irritation of colon mucosa by reducing laxity. Hence all these gunas of Panchamrut parpati make it very efficient in doing samprapti vighatana of Grahani roga[17]. So Panchamrita parpati is yogavahi, agnideepaka, grahi and is selected for the study. So here an effort is made to see whether Pachamrutparpati or Placebo treatment is more effective in the management of Grahani.

A. Status of trial

Patients are being recruited for the trial.

B. Declarations

1. Ethics approval and Consent to Participate: The Ethics Committee of Shri Krishna Ayush University, Kurukshetra, accepted the study (SKAU/ Acad/2022/6758).
2. Financial Implications: The financial allotment shall be given by Shri Krishna Ayush University for the study will be utilized andwill be completed within the financial limit provided by the institute.
3. Followed Guidelines: The common guidelines for clinical trials, known as the Declaration of Helsinki, are being followed in the conduct of this trial.

References

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Copyright

Copyright © 2024 Gahalawat Preeti, Lamba Neha, Kumari Neelam , Chaudhary Piyush. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.