An Experimental controlled clinical study to find the efficacy of Bhadradi kashaya administered orally and as Kala basti in the management of Sthulapramehi (Diabesity)

This is a comparative study to investigate the effect of BhadradiKashaya administered Orally and as Kala Basti on the gut microbiome andmetabolite pattern in Sthula Pramehi(Diabbesity) and Sthula(HealthyObese).

 Metabolomics is the comprehensive characterization of metabolites inbiological systems. The metabolomes comprisesof small intermediary molecules and products of metabolism, including thoseassociated with energy storageand utilization, precursors to proteins and carbohydrates, regulators of geneexpression, and signalling molecules.Metaboliccharacterization of type 2diabetes mellitus (T2DM) is crucial for the identificationof individuals at risk for developing diabetes andT2DM-related vascular complications as well as for monitoring disease progression.

In Ayurveda, Basti(medicineadministered through anal route) is one ofthe major procedures described under Panchakarmafor internalcleansing. The Bhadradi Aasthapanabastitherapy includes Poorvakarma- sthanikaabhyanga(External oil massage) followed by sthanika Nadiswedana(Sudation) which is followed by Pradhankarma Basti dana(administration of drug through anal route). As perayuvedic text Bhadradi asthapana Bastiishelpful ingetting relief from lakshana(symptom) of kamla(Jaundice), pandu(Anaemia), meh(Diabetes mellitus), medasvi(Obese)*, agni mandya(derange state ofmetabolism) kaphrogashan.*The aim of Bastikarmais to clean the body at both macro (gut) and micro channellevel up to the intracellular organelle and thus leading to a balancedstate of Doshasand Agniwhich in turn willhave a positive effect on gut physiology, digestion, improvement instrength, metabolism and hence resulting in a healthy state of body and mindas described in classical texts. Considering these factors, it is plannedto find out the impact of Basti Karmaon Gut microbiomeand their metabolites in a widely prevalent metabolic disease SthulaPramehi(Diabesity)as previous studies indicates that type 2 diabetes in humans is associatedwith compositional changes in gut microbiome.

Diet and lifestylemodification being an integralpart of Basti karmamay lead to the modification ofenvironmental microflora in a positive aspect for shaping the healthy humanmicrobiome and hence metabolite composition thus leading to the state of wellness. Thiswhole information gives a lead that Bastitherapyaims at modulating the gut functioning and thereby restoring thestate of homeostasis, improving digestion and metabolism in turn can be proved to be an effectivetreatment. Therefore, this study can investigate the role of Bastitherapyas described in Ayurveda byshowing its impact in the modulation of metabolites, biomarkers associated with obesity and T2DM and hence it can emerge as a proven modality oftreatment in variety of diseased conditions. In the sampraptiof Sthoulyaand Pramehainlater phase there is aggravation of Vatafor which Bastiis the mostpreferred treatment in Ayurveda; Further a specific Basticalled BadradiAsthapana Bastiis indicatedfor the pathological conditions like Sthoulya(Obesity), Prameha(Diabetes)hence this Basti is selected inthe modified form of Kalabastiin the present study on SthulaPramehi(patients with Diabesity) andthe same drugs of Bahdradi Aasthaapan Bastiwill be givenorally in both Sthula Pramehi(patients with Diabesity) and inhealthy obese to compare its effect when administered as Bastiand orally.

  OBJECTIVES OF THE RESEARCH PROJECT

 Primary:

• To compare the efficacy of Bhadradi Kashayawhen administered Orally and as Basti in the management of Sthula Pramehi(Diabesity)based on clinical parameters(sign and symptoms of Pameha), Biomarker and stool metabolites(SCFA’s).
• To evaluate change in body weight and BMI, WHR in the patients of Sthula Pramehi (Diabesity) as well as healthy Obese.

Secondary:

• To see changes in Gut microbiome diversity
• To evaluate the quality of life.

METHODOLOGY-

TYPE OF STUDY DESIGN - A randomized controlled clinical trial

SAMPLE SIZE CALCULATION â€“

This type of study is being done first time and further experiment procedure and test are costly. Therefore seeing the feasibility we have decided to take 15 individual in each group.

For recruitment in gr 1 and 2 Block Randomization will be used.

Group 1: Patient having lakshanaof Sthoulya and Prameha (administration of Bhadradi kasahay as Basti)

Group 2: Patient having lakshanaof Sthoulya and Prameha (Oral administration of Bhadradi kashaya)

No randomization will be required

Group 3 : Sthula without comorbdity like HTN otherwise healthy(administration of Bhadradi kasahay as Basti)

Total Sample Size =45

 DRUG DELIVERY REGIMEN (DRUG,DOSE DURATION, FOLLOW-UP, WITHDRAWAL)

In Group1&3

Procedure

Deepan-Pachan -Vaishvanar churna for 3 days

Sthanikaabhyanga - Tila taila for 9 days

Sthanika nadisweda - Dasmoola kwath for 9 days

Anuvasana Basti- Sarshapa taila for 6 days

Niruha Basti -Bhadradi kashaya for 9 days

Basti dravyas-

Kwath dravya- Bhadra(Katphala), Nimba, Kulatha, Arka, Koshataki (katutorai), Amruta(Guduchi), Amre(Devdaru), Sariva, Bruhati, Patha, Moorva,Aaragvadh, Vatsak(Kutaj)

Kalka dravya- Vacha, Madanphala, Sarshapa, Saindhev, Amar(Devdaru),Kushth, Ela,

Pippali, Bilva, Naagar(Shunthi)

Sneha dravya-  Sarshapa taila, Tila taila

Prakshep dravya- Yava kshar, Gomutra, Amla(Kaanji )

Saindhava

Madhu

In Group 2

Procedures

 Deepana- Pachan- Vaishvanar churna for 3days

Oraladministration of Bhadradi Kashayafor 30 days O.D emptystomach

Total Durationof study- 34 days

Total Duration of Procedures- 18 days

Follow Up- after 15 days of completionof treatment.

PARAMETER FOR ASSESSMENT OF STUDY OUTCOMe

• Reduction in Sign and Symptoms of Sthula Pramehi (Diabesity) patients (By questionnaire Scoring Pattern of CSIR-IGIB).

• Targeted Metabolite analysis of stool through LC-MS,

• Plasma Glucose level through intravenous blood sample of the patients.

• QOL Questionnaire

• Microbiota through 16s rRNA technology*.

Collection of specimens

• Faecal Sample
• Blood Sample*

*Note- Bloodsample(for molecular analysis simultaneously along with the blood sample to becollected for Plasma Glucoselevel test) and stool sample formicrobiome analysis will alsobe collected for future analysis if resources and time would allow.

RESPONSECALCULATION AND ASSESSMENT OF RESPONSE:

The primary outcome measure of this study is to determinethe response (R) of the patientsto the therapy and it isproposed to be measured in terms of the

• Reduction in sign and symptoms of Sthula Pramehi and plasma glucose levels.
• Reduction in WHR, BMI.
• Absence/reduction in the microbiome and metabolites associated with Diabesity and which are not  beneficial for metabolism.
• Presence/increase in microbiome and metabolites helping in the prevention of Diabesity and which  are beneficial for metabolism.