Studying Effectiveness of Individualised Homoeopathic Medicines Verses Berberis Vulgaris Mother Tincture in Management of Urolithiasis- A Comparative Study.

Urolithiasis is a most painful and prevalent urological disorders of the urinary system since prehistoric period. It is a global problem affecting people of all ages across all geographical regions. The prevalence and incidence of Urolithiasis is reported to be increasing across the world. Its increasing incidence makes it a major social and economic problem.                                                                                                                                                                             The percentage of incidence of Urolithiasis differs greatly in different parts of the world; annual approximate prevalence is 3-5percent and approximate life time prevalence is 15-25percent; in Asia it is 1–5percent.

Recent studies reveal the prevalence rate at 8.8 percent 34, and at 9.2 percent.35 Forecasts for the 2030s estimated a prevalence at 9.5percent. Urolithiasis affects about 12percent of the world population at some stage in their lifetime. In Indian population, about 12percent of them are expected to have urinary stones, out of which, 50percent may end up with loss of kidney functions.[1] In India, approximately 5–7 million patients suffer from kidney stone disease, and at least 1/1000 of the Indian population need hospitalisation due to urolithiasis

Most calculi occur in healthy young men, male female ratio 2:1.  The peak age of onset is between 20 to 30 years. Urolithiasis can remain asymptomatic for a long time, so it can be observed unexpectedly during an imaging examination .

The intervention  includes non-steroidal anti-inflammatory drugs (NSAIDs)  and opioids  for relieving  pain associated with  urolithiasis.  Both the  categories  of drugs  have been found to be equally effective although NSAIDs are known to cause potential gastrointestinal and renal side effects, whereas opioid analgesics require administration of antiemetic agents as they are known to cause nausea and vomiting along with urinary retention, constipation and respiratory depression.

Apart from the administration of drugs to prevent the formation and/or expulsion of the renal stones, the other approaches depending on the case are  extracorporeal  shock wave lithotripsy, ureteroscopy, percutaneous nephrolithotomy, laparoscopic surgery and open surgery. The limitations in the conventional system of medicine for treating this condition are the cost involved in the diagnosis with regard to the type of stone, metabolic disorder, invasive procedures and side effects of the medicines.

Homoeopathic  literature shows  the usefulness  of homoeopathic medicines in the expulsion and dissolution of renal stones. There are case reports reflecting the importance of individualisation and the effectiveness of homoeopathic medicines in the expulsion of renal stones.

Although there has been progress in minimally invasive surgical and interventional management of stone disease, recurrent episodes of flank pain due to obstructing urinary stones still result in frequent visits to the emergency room.

Homoeopathy is known for its holistic and individualised approach in  management of diseases, the management of urolithiasis patient will depend on presenting complaints. as this entity presence with varying symptomatology. this holistic modality can offer personalised treatment to every patient of urolithiasis. hence it is an attempt to compare effectiveness of indivisualised homoeopathy verses berberis vulgaris mother tincture.

Review of literature Urolithiasis is a disease characterized by the presence of stones in the urinary tract, whether in the kidneys, ureters, or bladder. Urolithiasis is a biomaterial that originates inside urinary tract as a result of aggregation of crystalline structures that build up in the nephrons of the kidney and it cannot be eliminated naturally. Various risk factors contribute in stone formation are high urine calcium level, obesity, hyperparathyroidism, gout, calcium supplements, hot climate, diet rich in meat, fish, eggs, milk, tomatoes, spinach, high salt intake etc. Apart from these deficiency of vitamin A, decrease level of urinary citrate, urinary statis and prolong immobilisation also contributes in calculus formation. They can cause severe pain, infection, and obstruction of urine flow. Urolithiasis are a common health problem, affecting about 12percent of men and 6% of women worldwide(6).They are a significant cause of morbidity worldwide, with a lifetime prevalence of 10-15percent in the general population. The prevalence of urolithiasis is increasing due to dietary and lifestyle factors, such as high intake of animal protein, sodium, and sugar, and low intake of fluids, calcium, and citrate(7).

This transformation finds evidence in the economic progression which reflects changes in socioeconomic level, lifestyle modifications and changing eating habits . Urolithiasis can have serious consequences for public health, such as increased health care costs, reduce The prevalence of the disease in industrialised countries has increased dramatically over the past d quality of life, and increased risk of chronic kidney disease and end-stage renal disease(8)

Urolithiasis, commonly known as kidney stones, are hard deposits made of minerals and salts that form inside the kidneys. . The stones vary in size, shape, and composition, and can be classified into several types based on their chemical makeup. The primary types of urolithiasis include calcium oxalate, calcium phosphate, uric acid, struvite, and cystine stones.(9) Calcium oxalate stones are the most common, constituting about 70-80% of all cases (10). These stones form when calcium combines with oxalate in the urine.

The etiology of urolithiasis is multifactorial, involving a combination of genetic, environmental, and metabolic factors. Metabolic abnormalities such as hypercalciuria, hyperoxaluria, hyperuricosuria, and hypocitraturia are common contributors to stone formation (14). Hypercalciuria, an elevated level of calcium in the urine, is found in up to 50percent of patients with calcium stones. Hyperoxaluria can be due to increased dietary intake or endogenous production.

The pathophysiology of urolithiasis involves supersaturation of the urine with stone-forming constituents, nucleation, crystal growth, and aggregation (15). When the concentration of stone-forming salts exceeds their solubility, they precipitate and form crystals. These crystals can adhere to the renal epithelium, particularly at sites of injury or Randall’s plaques, which are sub epithelial deposits of calcium phosphate(16) . Over time, these crystals grow and aggregate, eventually forming stones.

The clinical presentation of urolithiasis can vary widely. Small stones may be asymptomatic and discovered incidentally during imaging for other conditions. Symptomatic stones typically present with renal colic, characterized by severe, intermittent pain originating in the flank and radiating to the groin(17) (Rodgers, 2015). This pain is due to the stone causing obstruction and ureteral spasm. Other symptoms may include hematuria (blood in urine), nausea, vomiting, and urinary frequency or urgency if the stone is located near the bladder(18).

The diagnosis of urolithiasis involves a combination of clinical evaluation, laboratory tests, and imaging studies.

The management of urolithiasis depends on the size, location, and composition of the stones, as well as the severity of symptoms. Conservative management includes increased fluid intake, dietary modifications, and medications to manage pain and facilitate stone passage (21). Medical expulsive therapy with alpha-blockers such as tamsulosin can aid the passage of stones, particularly those located in the distal ureter(10)

For larger stones or those causing significant symptoms, interventional treatments may be required. Extracorporeal shock wave lithotripsy (ESWL) uses shock waves to break stones into smaller fragments that can be passed in the urine(10)

Concept of Individualisation: Individualized homeopathic treatment is based on the principle of selecting a remedy that matches the totality of symptoms and characteristics of each patient, rather than prescribing a common remedy for a specific diagnosis. This approach aims to stimulate the natural healing power of the individual and to address the root cause of the disease, rather than suppressing the symptoms.

.Previous Homoeopathy research

Rationale of the study Considering there aren’t many RCTs in homoeopathy, and it is crucial to have a significant sample size so that the generalizability of the trials is applicable. I aim to impart the real, evidence-based findings on the individualistic approach to patient care in the cases of urolithiasis.

Research question

1. Are individualised homoeopathic medicines more effective than berberis vulgaris mother tincture in treatment of urolithiasis?

2. Are individualised homoeopathic medicines  more effective than berberis vulgaris mother tincture in pain management /expulsion of stones

Primary hypothesis or Null hypothesis (H0) Individualised homoeopathic medicines are not effective than Berberis vulgaris mother tincture in treatment of Urolithiasis.

Alternative hypothesis (H1) Individualised homoeopathic medicines are more effective than Berberis vulgaris mother tincture in treatment of Urolithiasis.

aim and objective:

aim:     to compare effectiveness of inividualised homoeopathy medicine vs berberis vulgaris mother tincture in management of urolithiasis.

primary objectives: to determine effectiveness of individualised homoeopathy medicine in compare to berberis vulgaris mother tincture in management of urolithiasis.

to determine individualised homoeopathy medicine vs berberis vulgaris mother tincture in pain management expulsion of renal stone

Study design Experimental, single blind study

Study Type Prospective, single blinded, Randomised controlled trial

Study population It will consist of patients with confirmed diagnosis of urolithiasis. Aged more than 18yrs

Study setting The patients will be enrolled from the hospital attached to the homeopathic medical college tertiary health care center. Cases will be collected from OPD , IPD and community camps. Additional cases will be collected from personal OPD owing to the fulfilment of eligibility criteria

Study Duration study shall be for maximum 3 years

each case will be studied minimum for 1 year and maximum for 2 years

follow up of each case will be taken every month and as required

.

Sample Size The total sample size will be 120

Sample size was determined using the expected proportion of event / outcome in each group values of which are estimated from literature & using the formula,

For follow-up studies, to avoid loss by loss to follow up / attrition, 60 subjects will be considered in each group so that even after attrition, we would be able to achieve the required minimum sample size.

Sampling Technique Simple randomisation technique will be used.

random number generator from google

.

Eligibility criteria Inclusion:

• Age more than 18 years

• All genders

• Cases of urolithiasis confirmed by sonography or X-Ray KUB

• Bilateral as well as unilateral urolithiasis

• Size of the calculi less than 14mm

• Single and multiple stones

Exclusion:

• Advanced cases of urolithiasis with pathological changes in kidney

• Urolithiasis with chronic kidney disease

• Patients with renal failure

• Patients having anatomic urinary tract abnormality

• Patients with bladder cancer or malignancies

withdrawal criteria :-

• if renal calculi persists 6 month after initiation of treatment,

• if patient fails to adhere to study protocol consecutively for 3 follow ups ,

• patient not willing to be part of study at any given time will be withdrawn from study

criteria for outcome assessment :

• modified naranjo criteria

• USG/ X ray findings

method of measurement :

• appropriate statistical test will be applied at further distribution of data,

• distribution of data will be checked using Shapiro-wilk test

study instrument and Data collection tools • standard case record

• ultrasonography of abdomen and pelvis and or x-ray KUB

• method of data collection :-

• diagnosed cases of urolithiasis attending opd and community camps will be oriented about this study and those who give voluntary written consent will be included in the study.

• these patient will be divided in two groups , group 1, and group 2.

• a detailed case history will be taken of both the groups.

• after formulating the totality, group 1will receive individvualised homoeopathy medicine, posology will be decided as per susceptibility of the patient.

• group 2 will receive berberis vugaris mother tincture.

Treatment allocation Group 1-IHM arm: The patients received IHM in centesimal potencies along with dietary and lifestyle advice. Each dose consisted of 6–8 globules (no. 10) of cane sugar, medicated with a single drop of the indicated medicine (preserved in 90% v/v ethanol). Medicines were obtained from SBL Pvt. Ltd. ® – a Good Manufacturing Practice (GMP) certified firm. Medicines were instructed to be taken orally on clean tongue with empty stomach; dosage and repetition depended upon the individual requirement of the cases. Group 2-BV arm: This arm will receive berberis vulgaris mother tincture in individualised doses in 30 ml of normal water. The dose will be 10 drops in half cup of normal water thrice daily as per the need of the patient. It will be prescribed orally, along with dietary and lifestyle advice. Whole batch of the medicine will be obtained from SBL Pvt. Ltd.® a Good Manufacturing Practice (GMP) certified firm.

data management and analysis tools :

• data will be compiled in MS word using excel sheet

• statistical analysis will be done using appropriate statistical soft wear.

• descriptive statistics , frequency, percentage of numerical data and mean, and standard deviation of numerical data.

• normality of numerical data will be checked by Shaprio wilk test

Statistical analysis Statistical analysis will be performed with the help of statistical package for social sciences by IBM Corporation version 15.0. Descriptive statistics will be used for categorical data. Mean and standard deviation will be used for continuous data. Comparison between two groups will be done through parametric test if the data is normally distributed. Significance level of p<0.005 will be considered.

Quality of the study The quality of the study will be maintained by controlling the selection bias, single blind method, and intension to treat analysis. The selection bias will be averted by using simple randomisation technique. Patient names will be coded according to their group names. Single blind method will help to reduce the possibility of performance bias. Intention to treat analysis will be used to curb attrition bias. The study will abide to prespecified protocol and outcomes will be transparently reported at the end of the study.

Outcome assessment Outcome assessment will be done with the help of three parameter USG findings before and after

• Reduction in the size of calculi at 3-month,6 month and 9 months from baseline

• Percentage of patients who achieved the stage expulsion of stone and are stone free after treatment

• Duration taken to complete removal of stone

• Improvement in the scores of Likert pain scale

Ethics committee approval Ethics committee approval will be taken before commencing the study. The informed consent form will be approved from Institutional ethics committee. Confidentiality of the patient will be maintained throughout the study. Trial will be conducted in accordance of Declaration of Helsinki

Annexure CONSENT FORM

Title: Studying Effectiveness of Individualised Homoeopathic Medicine verses Berberis Vulgaris mother tincture in the management of Urolithiasis- A Comparative study

Name of the Principal Investigator: Dr. Prashant Digarse

Name of the Co-investigator: Dr. Manisha Solanki

Name of the Research Site: Dhondumama Sathe Homeopathic Medical

College, Department of Practice of Medicine

And

Shrimad Homeo Clinic

Laxmi Nagar Nagpur

Name of Research Organization: Dhondumama Sathe Homeopathic Medical

College, Department of Practice of Medicine

Introduction: I, Dr. Prashant Digarse, am conducting research on “Effectiveness of Individualised Homoeopathic Medicine verses Berberis Vulgaris mother tincture in the management of Renal Calculus disease- A Comparative study” I invite you to be part of this research.

Purpose of the research: In this study, we will assess the efficacy of Indivisualised homeopathic medicine in treatment of urolithiasis. The effect will be evaluated by assessing the change in size of calculi, patients who achieved stage of expulsion, duration taken to remove complete stone and improvement in likert pain scale. The responsiveness of patients to the Individualized homoeopathic medicine, will be monitored for a period of 52 weeks. Safety will be assessed through the identification of any side effects that appear during the course of the study.

Participant selection: Adult patients with urolithiasis who are older than 18 years old and have and have confirmed diagnosis of urolithiasis.

Study Procedures: The medicines, doses, and frequency will be decided by the physician according to the relevant case history. I will evaluate your physical status and monitor your overall health. Sonography results will be collected for the analysis. I will continue to monitor your health during the study duration and collect information about any side- effects that you may encounter. If there are any concerns, please talk to me.

Risks: Homeopathic medicines are well proven on human beings. Each individualised homoeo medicine are given to patients based on the symptom similarity of the medicine to the patient. Homeopathic medicines are approved by the National Commission of Homeopathy for safe use in humans. Every homeopathic medicine has been evaluated in human studies and has shown a good safety profile. No extreme side effects are observed by these medications. However, you will be closely monitored during the study period for any side effects. As this study is not covered under any insurance schemes, you will not receive any monetary benefits in the event of occurrence of side-effects.

Benefits: There is no direct benefit to your participation. Though it has been proven effective and safe compared to other non-homeopathic treatment, your participation will help us further provide answers to our research question about whether individualised homeopathic medicine is equally effective in urolithiasis. Your participation is completely voluntary, and you will not receive any monetary or non-monetary benefit for it.

Confidentiality: Your information from this research will be kept strictly confidential. Only regulatory authorities/study team will have access to the information.

Publications: The results of this research, except your confidential information, will be published in scientific journals. Your identity will not be revealed in any of the study-related publications.

Voluntary Participation: Your participation in this research is entirely voluntary. You may also stop participating in the research at any time. Your decisions will be respected. Refusal to participate or withdrawal from this research will not affect your regular treatment.

Who to Contact: If you have any questions related to this study, you can always reach the principal investigator or co-investigator

Dr. Prashant Digarse – 9325432300

Dr. Manisha Solanki - 9822839740

PART II: Certificate of Consent

Patient Initials: Date:

Principal Investigator: Dr. Prashant Digarse

I,________________________________________________________________hereby give consent to participate in this study entitled “Effectiveness of Individualised Homoeopathic Medicine verses Berberis Vulgaris mother tincture in the management of Renal Calculus disease- A Comparative study ”

(Please write initials in the box                 if you agree following).

I confirm that I have read the information

sheet for the above study and have had

opportunity to ask questions. All my questions have been completely answered by the investigator and I am satisfied with the answers.

I agree and understand that my participation in the study is voluntary.

I understand I have right to refuse to participate in the study

I agree not to restrict use of any data or results that arise from this study provided

they are used for scientific purpose, and I am aware that my identity will be kept

confidential.

I agree to cooperate with the investigator.

I agree to join this study.

Name of the Patient                                       Date               Signature/Left Thumb imprint

Name of the witness                                      Date                Signature of Witness

Name of the Investigator                               Date                Signature of Investigator

CASE TAKING FORMAT FOR THE DISSERTATION (DATA COLLECTION)

Preliminary data

Name                                                                                   Age

Gender.                                                                                Occupation

Marital status.                                                                       Phone

• Chief complaint

• Origin duration and progress

• Associated complaints

• Origin duration and progress of associated complaints

• Past history

• Family history

• Personal history

• Diet

• Appetite

• Desire

• Aversion

• Thirst

• Bowel

• Urine

• Perspiration

• Sleep

• Dreams

• Habit

• Menses

• Thermals

Mind

• General examination- pallor, icterus, oedema, cyanosis, clubbing, lymphadenopathy.

Vital data

Pulse

Temp

B.P

RR

Local Examination

• Systemic examination

CVS

CNS

R/S

P/A

• Investigations

• Diagnosis

• Totality of symptoms

• Final remedy

• Prescription

• Auxiliary line of treatment and follow up

Patient information sheet

What is urolithiasis?

Urolithiasis, commonly known as kidney stones, are a prevalent urological condition in central India. The formation of kidney stones is a complex process influenced by various factors, including diet, fluid intake, genetics, and metabolic abnormalities. There are different types of kidney stones like Calcium Oxalate Stones, Calcium Phosphate Stones, Uric Acid Stones, Struvite Stones.

A kidney stone usually remains asymptomatic until it moves within the kidney or passes into one of the ureters (the tubes connecting the kidneys and bladder). At that point, you may experience Severe, sharp pain in the side and back, below the ribs.Pain that radiates to the lower abdomen and groin. Pain that comes in waves and fluctuates in intensity. Urinary Symptoms like Pink, red, or brown urine due to The presence of blood in the urine due to irritation caused by the stone, Cloudy or foul-smelling urine, Discoloration or unpleasant odor. Increased frequency of urination, Feeling the need to urinate more often than usual or passing urine in small amounts. Burning sensation during urination which is Due to inflammation or irritation.Other Signs and Symptoms might include Nausea and vomiting Especially if the stone causes significant discomfort. Fever and chills, If there’s an associated urinary tract infection.

Homoeopathy is a highly systematic method of treatment powerfully stimulating the body’s vital force to cure illness. It does not treat the disease but the diseased individual. It helps to alleviate the symptoms of the patients at the physical and the mental level and thereby gives relief to the patient.

Detailed information of the patient is required and then a prescription is made. This method is useful in acute as well as chronic ailments. Acute ailments respond quickly to the treatment but chronic ailments might take some time. In this system of medicine the disease is cured from its root so it does not appear again. The patient is considered as a whole, and not just the part/ organ affected.

Homoeopathic medicines are safe and effective medicines. The average duration of treatment will last up to 1year. Complete care will be taken not to cause discomfort to you during the study period.

What will be my role during the treatment period?

You are expected to come for regular follow-ups, so that there are no gaps in the treatment plan. Regular consumption of medicines as prescribed by the doctor is essential. Any advice given by the doctor as regards diet, exercise, rest, etc. should be followed for best results.