An open label double arm randomized controlled comparative Clinical Trial to evaluate the safety & effectiveness of Zandu Kutaja Ghana Vati in comparison to Zandu Kutaja Ghana Vati along with Zandu Mugdha Rasa in the management of Atisara

An open label double arm randomized controlled comparative Clinical Trial to evaluate the safety & effectiveness of Zandu Kutaja Ghana Vati  in comparison to Zandu Kutaja Ghana Vati  along with Zandu Mugdha Rasa in the management of Atisara

Introduction:

Functional diarrhea is a common gastrointestinal disorder characterized by frequent loose stools without any underlying organic cause, presents a significant health burden in India.

Its prevalence is exacerbated by dietary habits, lifestyle factors, and a lack of awareness among healthcare professionals and patients alike.

While existing Ayurvedic treatments focus primarily on symptom management, there is a pressing need for more rigorous clinical trials to explore effective therapeutic options tailored for faster recovery and a cost effective option

The present trial can facilitate a short time bound intervention of functional diarrhea, paving the way for evidence-based Ayurvedic interventions and improved patient outcomes.

Need for the study:

The increasing prevalence of functional diarrhea, particularly in India, highlights an urgent need for effective management strategies.

Ayurveda, the traditional system of medicine in India, offers a unique approach to treating gastrointestinal disorders, emphasizing the balance of bodily energies (doshas) and the integration of dietary, lifestyle, and herbal interventions.

There is limited empirical evidence supporting Ayurvedic treatments for functional diarrhea.

Conducting systematic studies can establish a scientific basis for these practices.

Methodology:

Details of triala nd control drugs:

Kutaja Ghan vati is an antidiarrheal drug and is very effective in treating acute and chronic cases of diarrhea due to various etiologies.

Ingredients:

1. Kutaja (Holarrhena antidysentrica) – 48g

2. Ativisha (Aconitum hetrophyllum) – 12g

3. water – 768ml

B. Mugdha Rasa is also an antidiarrheal drug and helps in managing symptoms associated with diarrhoea, nausea, vomiting

Ingredients:

1. Parada – 25mg

2. Khatika – 50mg

Hypothesis and Research Question:

Alternate Hypothesis :

Zandu Kutaja Ghana Vati and  Zandu Mugdha Rasa in combination is effective in the management of Atisara (Functional Diarrheoa)

Null Hypothesis :

Zandu Kutaja Ghana Vati and  Zandu Mugdha Rasa in combination is not effective in the management of Atisara (Functional Diarrheoa)

Research Question:

Whether Zandu Kutaja Ghana Vati and  Zandu Mugdha Rasa in combination is effective in the management of Atisara (Functional Diarrheoa)?

Materials and Methods:

Subjects who fulfill the Inclusion criteria will be included in the study

Assessment Criteria :

Rome IV Criteria for Functional Diarrhea

Atisara lakshana

Gastrointestinal Quality of Life (day 1 and day 7)

Laboratory Investigations details : CBC, ESR, LFT, RFT

Diagnostic Criteria: Rome IV Criteria for Functional Diarrhea

Recurrent Diarrhea:

Frequency: The patient experiences loose or watery stools at least 3 times per day.

Duration: Symptoms should be present for at least 3 months, with onset at least 6 months before diagnosis.

Patients meeting criteria for Diarrhoea predominant IBS should be excluded (That is, Greater than 25% of bowel movements with Bristol stool types 6 or 7 and less than 25% bowel movements with Bristol stool types 1 or 2)

Absence of Organic Causes:

Diagnostic evaluation should rule out organic causes of diarrhea, such as infections, inflammatory bowel disease, celiac disease, and malignancies.

Symptoms:

Characteristics: Symptoms often include urgency, frequent bowel movements, and the need to defecate immediately after meals.

Consistency: The stools are typically loose or watery.

Impact on Daily Life:

Functional Impact: The diarrhea affects the individual’s daily functioning or quality of life

Study design: Single Centre, Open Labelled, double arm, randomized controlled clinical trial.

 

Site of study: Research OPD at Shri Dhanwantry Ayurvedic College and Hospital, Sector 46-B, Chandigarh

 

Study duration:

Period required for pre-trial preparation: 45 days (Including drug preparations)

Period which may be needed for collecting the data: 3 months

Period that may be required for analyzing the data: 1 month

No of groups: 2 groups

Group A- Standard control group– Zandu Kutaja Ghana Vati (30 subjects)

Group B- Trial group- Zandu Kutaja Ghana Vati with Zandu Mugdha Rasa (30 subjects)

Inclusion Criteria:

•Clinical presentation of Functional Diarrheoa symptoms

•Patients with Atisara lakshana

•Patients with either sex, 18 to  60 years age

•All patients must agree not to share medication

•Patients willing to participate and sign an informed consent

•Understands and agrees to comply with planned study procedures

•Agrees to provide sample for testing as per protocol

Exclusion Criteria:

•Chronic, Severe, Unstable, Uncontrolled co-existent Medical illness such as Diabetes, Hypertension, Cardiac disorders, liver, kidney disorders and lung Disorders or other

disease of concern which may put the patient at increased risk during the study •Active cancer diagnosis, on palliative treatment or requiring current therapy with antimetabolic agents, immunotherapy or radiotherapy.

•Patients on parenteral nutrition

•Patients with known sensitivity or contraindication to any of the ingredients of study medication

•History of bleeding haemorrhoids, haemoptysis, acid peptic diseases, ulcers and pulmonary diseases (tuberculosis, asthma, etc.)

•Pregnancy and lactation

•Participation in a drug interventional clinical drug trial of any nature in the three month period

•Patients who are either on Allopathy medicines or on other AYUSH medications

Dosage of Medication:

Group A- Standard control group will be administered Zandu Kutaja Ghana Vati 2 tablets twice daily regularly after meals along with luke warm water

Group B- Trial drug Zandu Mugdha Rasa 1 tablet and Zandu Kutaja Ghana Vati 2 tablets twice daily regularly after meals along with luke warm water

•Total duration of the therapy: 7 days

•Follow up: Baseline, 3rd day (with medication) and 7th day (without medication for follow up)

•Randomization : R and Python  programming languages will be used to generate the random number sequence . The Participants will be  randomized  to 2 study groups in the

ratio of 1:1.

Data analysis : The collected data from this randomized controlled  trial (RCT) will be analyzed using both descriptive and inferential statistical methods. Descriptive statistics,

including mean, standard deviation, and frequency distribution, percentage, will summarize baseline clinical  characteristics and relevant variables. Inferential analyses will

include, Independent sample t-test. For categorical data, Chi-square or Fisher’s Exact Test will assess associations between variables , Paired-t test can be used to assess

treatment efficacy within specific groups. Depending on data distribution, non-parametric tests such as  Mann-Whitney U test, Wilcoxon signed rank test  will be employed

. SPSS version 27 and Jamovi version 2.6.2.0,will be our primary analysis tools  with isupplementary analyses in R and Python for statistical computing and for data visualization

Statistical significance will be set at p < 0.05.

Research Outcome:

•Trial drug Zandu Mugdha Rasa 1 tablet and Zandu Kutaja Ghana Vati 2 tablets twice daily regularly after meals along with luke warm water may be effective in managing

the symptoms of Functional Diarrhea

•The proposed study on Ayurvedic management of functional diarrhea could yield several significant outcomes that contribute to both clinical practice and the body of

knowledge in gastroenterology and alternative medicine.