|Year : 2019 | Volume
| Issue : 3 | Page : 139-149
Lycopodium clavatum for the management of urolithiasis: A randomised double blind placebo controlled trial
Rupali Bhalerao1, Praveen Oberai1, Pritha Mehra2, Yogendra Rai2, Gurudev Choubey3, Amulya Ratna Sahoo4, AK Majumder5, Mahesh Sah6, AK Gupta7, AK Tyagi2, VA Siddiqui1, Arvind Kumar1, Raj K Manchanda1
1 Central Council for Research in Homoeopathy, New Delhi, India
2 Dr. D. P. Rastogi Central Research Institute of Homoeopathy, Noida, Uttar Pradesh, India
3 Clinical Research Unit (H), Siliguri, West Bengal, India
4 Drug Proving Unit, Bhubaneswar, Odisha, India
5 DAC Regional Research Institute of Homoeopathy, Kolkata, West Bengal, India
6 Homoeopathic Drug Research Institute, Lucknow, Uttar Pradesh, India
7 Regional Research Institute (H), Shimla, Himachal Pradesh, India
|Date of Submission||17-Apr-2019|
|Date of Acceptance||12-Jul-2019|
|Date of Web Publication||4-Oct-2019|
Dr. Praveen Oberai
Central Council for Research in Homoeopathy, 61-65, Institutional Area, Janakpuri, New Delhi
Dr. Pritha Mehra
Dr. D. P. Rastogi Central Research Institute of Homoeopathy, A 1/1, Sector 24, Noida, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Background: Urolithiasis is the most common disease of urinary tract found worldwide. There are several approaches for the treatment of urolithiasis that include the use of various synthetic and natural drugs and/or surgery in the conventional system of medicine. Objective: This study was taken up to evaluate the efficacy of Lycopodium clavatum in the management of urolithiasis. Materials and Methods: A multicentric, randomised, double-blind, placebo-controlled trial was conducted. Patients having symptomatology like Lycopodium clavatum were enrolled after screening and repertorisation as per the inclusion and exclusion criteria. During acute renal colic, despite group allocation, the patients were either prescribed the indicated homoeopathic medicines or conventional medicine. The analysis was carried out with an intention-to-treat approach, and missing values were handled using Last Observation Carry Forward method. Results: There was no statistical significance between the groups (P = 0.31) in reference to the number of cases in which stones expelled during the trial. The mean size of single stone expelled was 9.4 ± 4.9 and 13.9 ± 2.2 in Verum and Placebo groups, respectively (P= 0.12). There was also no significant difference in the mean size of mean size of multiple stones; in Verum group (10.1 ± 5.3) and Placebo group (16.1 ± 9.1) (P = 0.11). For assessment of pain and dysuria, Visual Analogue Scale was used, and a statistically significant difference was found between the groups (P = 0.039) for pain, and positive trend for Homoeopathy was noted for dysuria. A verified symptom syndrome of Lycopodium clavatum has been observed. Conclusion: Future studies with pragmatic study design and individualistic Homoeopathy can be undertaken to assess the effectiveness of treatment in urolithiasis.
Keywords: Calculi, Colic, Homoeopathy, Lycopodium clavatum, Non-steroidal anti-inflammatory drug, Urolithiasis
|How to cite this article:|
Bhalerao R, Oberai P, Mehra P, Rai Y, Choubey G, Sahoo AR, Majumder A K, Sah M, Gupta A K, Tyagi A K, Siddiqui V A, Kumar A, Manchanda RK. Lycopodium clavatum for the management of urolithiasis: A randomised double blind placebo controlled trial. Indian J Res Homoeopathy 2019;13:139-49
|How to cite this URL:|
Bhalerao R, Oberai P, Mehra P, Rai Y, Choubey G, Sahoo AR, Majumder A K, Sah M, Gupta A K, Tyagi A K, Siddiqui V A, Kumar A, Manchanda RK. Lycopodium clavatum for the management of urolithiasis: A randomised double blind placebo controlled trial. Indian J Res Homoeopathy [serial online] 2019 [cited 2020 Jun 2];13:139-49. Available from: http://www.ijrh.org/text.asp?2019/13/3/139/268517
| Introduction|| |
Humankind has been afflicted by urinary stones dating back to 4000 BC, and it is the most common disease of urinary tract. Urolithiasis is a problem found worldwide in every culture, racial group and geographic location. The incidence and prevalence rates of kidney stones may be affected by genetic, nutritional and environmental factors. Globally, the prevalence and recurrence rates of kidney stone disease are increasing, with limited options of effective drugs. Urolithiasis affects about 12% of the world population at some stage in their lifetime. In Indian population, about 12% of them are expected to have urinary stones, out of which, 50% may end up with loss of kidney functions. 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 kidney stone diseases. In the geographical region of India, two distinct 'stone belts' have been identified: North India forms the 'First Stone' belt and parts of Maharashtra, Gujarat and Jabalpur in Madhya Pradesh form the 'Second Stone' belt.
The symptoms of kidney stone are related to their location, whether it is in the kidney, ureter or urinary bladder. The signs and symptoms of the stone disease comprise renal colic, flank pain, haematuria, obstructive uropathy, urinary tract infections, blockage of urine flow and hydronephrosis. These conditions may result in nausea and vomiting with associated suffering from the stone event. Thus, the treatment and time lost from work involve substantial cost imposing an impact on the quality of life (QOL) and the nation's economy. Apart from these, kidney stones are associated with an increased risk of chronic kidney diseases, end-stage renal failure, cardiovascular diseases, diabetes and hypertension.
There are several approaches for the treatment of urolithiasis that include the use of various synthetic and natural drugs in the conventional system of medicine. Once the presence of urinary stones is confirmed and their location, size and type are established, medical intervention comes into play that includes treatment by drug therapy or surgical removal of the stones. 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. Medical expulsive therapy is used to allow spontaneous expulsion of moderately sized distal ureteral calculi from the urinary tract. Similarly, there are different groups of drugs for different types of calculi with their potential side effects or limitations. 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.[5(i)] 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.[5(ii)]
According to a survey conducted in India, 62% of the current Homoeopathy users have never tried conventional medicines for day-to-day health problems and 82% would not switch to conventional treatments, unless it is an emergency. Presently, Homoeopathy is accepted as a system of gentle healing. The inherent strength of the system makes it a safe therapy, eco friendly and free from adverse side effects. A retrospective study on the prevalence and likelihood ratio of symptoms in patients with good therapeutic response to Lycopodium clavatum also reflects the action of this drug on kidney stones. 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.,,,
Another study, a preliminary investigation on ultra-high diluted Berberis vulgaris in experimental urolithiasis, showed that the root-bark of homoeopathic medicine Berberis vulgaris has strong anti-urolithiasis potential at ultra-diluted dose. Another in vitro study conducted using homoeopathic medicine signifies Berberis vulgaris to be a potent drug against calcium oxalate crystallisation both at the level of nucleation and aggregation.
The Central Council for Research in Homoeopathy conducted a multicentric observational study to evaluate the effectiveness of Homoeopathy in urolithiasis, which showed positive results. The medicines found most useful were Lycopodium clavatum in 40.9% (n = 90) of cases; Sulphur in 12.3% (n = 27) of cases; Pulsatilla nigricans in 8.2% (n = 18) of cases; Nux vomica in 6.2% (n = 14) of cases and Cantharis vesicatoria in 5.9% (n = 13) of cases.
With this background and keeping in view the results of a previous study, this double-blind, placebo-controlled study has been undertaken by the Council to evaluate the efficacy of Lycopodium clavatum in the treatment of urolithiasis and to access the effectiveness of homoeopathic medicines in the treatment of acute renal colic. Further, the symptoms of Lycopodium clavatum medicine were also verified.
| Materials and Methods|| |
Study design, setting and duration
This multicentric, randomised, double-blind, placebo-controlled trial was conducted at seven centres, namely the Central Research Institute (H), Noida (Uttar Pradesh); the Homoeopathic Drug Research Institute, Lucknow (Uttar Pradesh); the Regional Research Institute (H), Shimla (Himachal Pradesh), Jaipur (Rajasthan) and Puri (Odisha); Dr. Anjali Chatterjee Regional Research Institute (H), Kolkata (West Bengal) and the Clinical Research Unit (H), Siliguri (West Bengal), between July 2012 and March 2015. The four study sites in the first stone belt and three study sites in the northeast region were considered keeping in view the prevalence of the disease condition as per the two belts mentioned in the introduction section. The investigators were given training on the study protocol before the initiation of the study. The data of cases wherein Lycopodium clavatum was prescribed in the observational study of Council  were investigated, and symptom syndrome was framed subsequently and provided to the study investigators as ready reference before initiating this study.
The study protocol and procedure followed were in accordance with ethical standards of Council, Helsinki Declaration of 1964 for human experimentation, revised in October 2000 and with Good Clinical Practice in India. Data of trial were reported as per the Reporting Data on Homoeopathy Treatments Guidelines.
Protocol clearance was obtained from the Institutional Ethic Committee of the Council and registered with the Clinical Trials Registry of India with trial registration no. CTRI/2011/12/002210 dated 8.12.2011. Written informed consent for participation in study and use of patient data for research and educational purposes was obtained from participants before enrollment in the study.
During the enrolment period of the study, patients reporting at the outpatient department (OPD) of the seven research centres were screened (preliminary and detailed) on the basis of the inclusion and exclusion criteria. Patients having symptomatology like Lycopodium clavatum after repertorisation were enrolled in the study by Investigator without deviating from the homoeopathic principle of 'Individualisation'. Each participant was verbally explained about the study, with the help of a patient information sheet, and thereafter, a written informed consent was obtained from them for voluntary participation in the study. However, they were free to withdraw the consent from the study at any point of time.
- Cases with radiographic evidence (X-ray and ultrasound of kidney/ureter/bladder [KUB]) of calculi in KUB (both symptomatically and asymptomatically diagnosed cases) with or without mild hydronephrosis
- Size of calculi: In the case of single calculus, 5 mm or above
- In the case of two or more calculi, one calculus must be 5 mm or above
- Both sexes of age between 18 and 60 years
- Written informed consent from the patient.
- Cases with moderate/severe hydronephrosis
- Creatinine levels >2 mg%
- Recurrent urinary tract infections
- Acute retention of urine for >24 hours
- Cases with hyperparathyroidism
- Cases with gross developmental defects or structural abnormality of kidney
- Cases with other systemic diseases such as cardiovascular and endocrinal diseases or systemic infections or on other treatment therapies
- Impacted calculus, staghorn calculus
- Cases not having Lycopodium clavatum symptomatology
- If any exclusion criteria develop during the study, the case will be excluded.
Randomisation and group allocation
Patients fulfilling the eligibility criteria were enrolled and randomised into two groups – verum i.e., Lycopodium clavatum, and placebo group. The allocation in the respective groups was as per random numbers generated with the help of computer-based software available at www.randomizer.org (last accessed on 12 June 2012). Randomization chart was generated by statistician involved in study. They received either of the intervention i.e., Lycopodium clavatum or placebo (1:1 ratio).
As this is a multicentric study, the medicine and placebo were prepared in four lots i.e., A, B, C and D, which were sent to all the centres. Two lots belonged to verum and two belonged to placebo groups. This was done to reduce the bias to the extent possible among the site investigators.
Both groups were assessed on same parameters. Participants and Investigator were blinded during the study period. Concealment was assured as the pharmacist had dispensed medicine to the patients from lots A, B, C and D as per the medicine lot assignment envelop provided by the Council. Pharmacist's contact with the patient was limited to dispensing and instruction regarding the administration of medicine. His/her contact with the investigator was limited to the communication of the identity of the patient and the medicine to be prescribed. The investigator was not aware to which group and to which medicine lot the patient had been assigned.
Unblinding of the study was to be done only after the study got completed at all the centres, except in the case of reporting of any adverse event.
History of each individual case was recorded on a structured pro forma followed by analysis and evaluation of the symptoms; totality of the symptoms was formed and repertorised using Synthesis repertory is printed version of Software program RADAR. Archibel, a Zeus Soft company at Belgian manufacturer Rapid Aid to Drug Aimed Research (RADAR). Patients those who were fitting to Lycopodium clavatum drug picture were enrolled in the study, and others were treated in the OPD. As per the randomisation chart, the patients were allocated to any one of the four medicine lots, two lots each contained either Lycopodium clavatum or placebo.
The potency was selected as per the susceptibility of the patient and followed serially by next higher potency as per the need of the case. A single dose was prescribed in each case, and medicine was repeated depending on the intensity of the complaints. The patients were advised to report for follow-up as per the need. The patients were followed up at one-month interval, and case was assessed for the respective symptoms for example, pain and dysuria by the investigator. Repetition of the medicine was done in the same or higher potency as per the need.
During acute renal colic, despite group allocation, the patients were prescribed the indicated homoeopathic medicines, and if not managed by Homoeopathy, they were either referred to the consultant or were left free to take any medication for acute phase. This information was also recorded. After the completion of acute episode, they received medicine from the allocated group of treatments till completion of 1 year, and then data were analysed.
The sample size was calculated keeping in view the outcome of the earlier observational study on urolithiasis conducted by the Council (2005–2010). The effect size in the previous study was 0.5, so in the present study also, using an effect size of 0.5 with the power 0.85, α = 0.05 and intervention:placebo at 1:1, the sample size was calculated as 59:59. Thus, a total of 118 cases were required for the final analysis. It was considered that there might be an estimated 25% of dropouts, and few of the cases may have an acute phase and will be then considered as a subgroup, and hence the total sample size should be 180. Thus, cases to be enrolled at each centre were 15:15 (verum: placebo).
The primary outcome measure was clinical cure i.e., dissolution/expulsion of renal calculus with radiological evidence (X-ray and ultrasound KUB) of no calculus in the urinary tract. Each patient enrolled in the study was assessed with laboratory parameters at every 3rd, 6th, 9th and 12th month. If patients reported of any expulsion in between the follow-up, ultrasound examination was done to assess.
The secondary outcome parameters were relief in pain (flank) and dysuria as per the Visual Analogue Scale (VAS) from 0 to 10, where 0 indicates no pain and 10 indicates maximum severity, assessed at every month follow-up. The World Health Organization-QOL (WHO-QOL) BREF was assessed at baseline and at 12 months for changes in QOL parameters.
The analysis was carried out with intention-to-treat (ITT) approach, and missing values were handled using Last Observation Carry Forward (LOCF) method. IBM at Bengaluru, India manufactured Statistical Package for Social Sciences (SPSS) software, version 20 was used for carrying out the statistical analysis. Comparison between verum and placebo groups was performed at baseline to assess randomisation effect using an independent t-test for continuous variables and Chi-square test for ordinal data as applicable. Repeated-measures ANOVA was applied to assess the difference between the groups at different time points. Primary and Secondary outcome measures were assessed using Chi square test and independent t-test respectively. In all the analyses, P < 0.05 was considered statistically significant.
| Results|| |
Between July 2012 and March 2015, a total of 753 patients were screened, and 134 patients were enrolled from seven different institutes/units of the Council located all over India. Out of these 753 screened cases, 619 were excluded due to various reasons as reflected in [Figure 1]. Due to difficulties in achieving the sample size, an interim analysis of the study was performed, and it was decided by the regulatory committees (Special Committee of Clinical Research and Scientific Advisory Committee of the Council) to stop the enrolment of patients and complete the follow-up of enrolled cases. Finally, 134 patients, 63 in Verum group and 71 in Placebo group, were considered for primary outcome analysis. Baseline characteristics were similar for both groups. The mean age of the patients was 35.8 ± 11.6 years in the Verum group and 35.5 ± 11.9 years in the Placebo group. A total of 47 (74.6%) patients and 52 (73.2%) patients were male and 16 (25.4%) patients and 19 (26.8%) patients were female in each respective group. The duration of illness i.e., urolithiasis, was 1.7 ± 3.5 years in Verum group and 1.4 ± 2.8 years in Placebo group. Other demographic details are summarised in [Table 1].
|Table 1: Comparison of demographic characteristic of verum and placebo groups at baseline|
Click here to view
At baseline, 36 (57.1%) patients in the Verum group and 32 (45.1%) patients in the Placebo group had single stone with a mean size of 8.3 ± 3.8 mm and 9.4 ± 6.7 mm, respectively. Right-sided kidney stones were present in 15 (23.8%) patients of the Verum group and 21 (29.6%) patients in the Placebo group; while bilateral stones were present in 19 (30.2%) patients of the verum group and 17 (23.9%) patients of the Placebo group. Other stone-related details such as stone size and location-wise size are described in [Table 2].
|Table 2: Comparison related to number of stones, position, location and size of verum and placebo groups at baseline|
Click here to view
Efficacy results: Intention-to-treat analysis
The results were assessed after completion of 1-year follow-up, and ITT analysis was considered as in few cases the stone got expelled/dissolved before 1 year and others were dropped out due to various reasons. Thus, LOCF was considered for all the 134 cases enrolled in the study.
Stone was expelled in 12 (19.0%) cases in the Verum group and in 9 (12.7%) cases in the Placebo group. No significant difference was found between the groups. The mean size of single stone expelled in the Verum group was 9.4 ± 4.9 mm and 13.9 ± 2.2 mm in the Placebo group; the mean size of multiple stone was 10.1 ± 5.3 mm in the Verum group and 16.1 ± 9.1 mm in the Placebo group, which was not found to be statistically significant (P = 0.12 and P= 0.11) respectively. Although there was no statistical difference in the size of stone expelled and number of stones (single/multiple) expelled in the Verum and Placebo groups, patients reported symptomatic relief. Details of outcome assessment results are summarised in [Table 3]. The WHO-QOL Bref was used for the assessment of QOL; no difference was found between the groups [Table 3]. For the assessment of pain and dysuria, VAS was used, and statistically significant difference (P = 0.039) was found between the two groups for pain at different time points [Figure 2]. The positive trend in favour of Homoeopathy was found in dysuria [Figure 3]. For acute pain management, patients were advised to take their desired intervention, and the events were recorded. A total of 15 patients were recorded for acute pain: nine patients were from the Verum group and six were from the Placebo group. Eight of the 15 patients were prescribed homoeopathic intervention such as Belladonna and Magnesia phosphorica and seven were managed by conventional medicine.
|Table 3: Comparison of outcome measures between verum and placebo groups|
Click here to view
Verified Lycopodium clavatum symptoms
To achieve the secondary objective of the study, Lycopodium clavatum symptoms for all the 63 cases in the Verum group were assessed in relation to medicine-specific symptoms found in the observation study of urolithiasis conducted by the Council  and for the prevalence and likelihood ratio of Lycopodium clavatum symptoms' study.
The symptom syndrome of Lycopodium clavatum confirmed in this study is mentioned in [Table 4].
| Discussion|| |
This was a double-blind, randomised, placebo-controlled study, and the physician was to prescribe Lycopodium clavatum on the basis of individualisation. These patients not covering the symptomatology of Lycopodium clavatum were excluded from the study and were treated in the general OPD. Enrolment in the study was difficult as many cases, though reflecting Lycopodium clavatum symptomatology, were excluded as the size of the renal calculus was <5 mm, which can be seen from the large gap in the screened (n = 753) and enrolled (n = 134) cases. Strict eligibility criteria affected the enrollment and further affected the external validity of study.
There was a heavy loss to follow-up during the study period, which made assessment of results tough. Another limitation was that after selecting Lycopodium clavatum as medicine for patients at baseline, the investigators were supposed to continue the same medicine with suitable potencies during follow-up period, which contradicts the routine homoeopathic practice where there could be requirement of change in prescription. It was observed in one of the reviews that, often, homoeopaths do not find the correct remedy at once and/or change the remedy as the clinical picture changes. In a case of a double blind trial, a homoeopathic practitioner often encounters the challenge that, changes occuring due to any three possibilities, namely, a failure to reach correct similimum, any symptom shift in patients, totality or patient being a participants of a placebo group. Thus, physician bias to enroll non-Lycopodium clavatum cases in this study cannot be ruled out.
In an observational study of the Council  on urolithiasis, there was expulsion of stone in 41% of cases, whereas in the present study, stone was expelled in only 19% of cases. The difference in the results could be because of the study design. In the observational study, though the prescription was individualised, there was freedom to the investigators for change of prescription or potency of medicine. This was not applicable in the current study. In the present study, double-blind, placebo-controlled methodology was adapted, which is the gold standard in conventional medicine for clinical trials, but it seems that, this methodology may not be suitable for Homoeopathy practice, which is reflected in other homoeopathic studies.,
This observation has been in consonance with a study where the impact of study quality on outcome in placebo-controlled trials of Homoeopathy was assessed, and it was found that studies with better methodological quality tended to yield less positive results.
In the present study, significant reduction in flank pain and pain during micturition was found between the groups at different time points. This is in agreement with another homoeopathic pilot study on urolithiasis.
In the present study, 12 symptoms of Lycopodium clavatum were found in accordance with a previous study of the Council, and eight symptoms were confirmatory as per the study of the prevalence and likelihood ratio of Lycopodium clavatum symptoms' study. Thus, these symptoms can be considered while prescribing Lycopodium clavatum in any disease condition. Digestive troubles and urinary complaints were present in almost all the cases of urolithiasis.
Patients in the placebo group had undergone the homoeopathic case history recording procedure that might contribute considerably to a possible treatment effect, decreasing the likelihood of identifying differences between the groups. To achieve efficacy results using Lycopodium clavatum in urolithiasis, a pragmatic approach is suggested for future studies.
| Conclusion|| |
In the present study setting, Homoeopathy medicine Lycopodium clavatum did not show significant results in expulsion/dissolution of the renal calculi in comparison with placebo. Thus, the need of rigorous methodology of trial, external validity and application of single medicine in the treatment of such conditions where acute episodes and change in symptomatology are expected, should be thought of. The significant difference in the flank pain and positive trend in dysuria in favour of Homoeopathy are encouraging, and future studies with pragmatic study design and individualistic Homoeopathy can be undertaken to assess the effectiveness of Lycopodium clavatum in the treatment of urolithiasis. Moreover, this study may help to frame a strategic plan for treatment of such cases.
The authors are thankful to Dr. Vikram Singh, former Deputy Director, for his guidance in carrying out the project. The authors appreciate Dr. Bhavan Singh, Research Officer/S-4, and Dr. Ram Prakash Gupta, Research Officer/S-4, for their contribution in maintaining the follow-up of patients. Thanks are also extended to Dr. Anupriya, Senior Research Fellow (H), CCRH Hqrs. for maintaining the records for 6 months. The authors are also grateful to Senior Research Fellows (H) attached in the study at the respective centres for their contribution in collecting the data. The authors are thankful to Mrs. Maya Padmanabhan, Former Statistical Assistant for extending help during the drafting of the protocol. The authors thankfully acknowledge the patients who participated in the study and cooperated during follow-up.
Financial support and sponsorship
Central Council for Research in Homoeopathy, New Delhi under Ministry of AYUSH, Government of India.
Conflicts of interest
| References|| |
Alelign T, Petros B. Kidney stone disease: An update on current concepts. Adv Urol 2018;3068365.
Niemann T, Kollmann T, Bongartz G. Diagnostic performance of low-dose CT for the detection of urolithiasis: A meta-analysis. AJR Am J Roentgenol 2008;191:396-401.
Ganesan T, Ravi DB, Vasavan J, Khurana A, Nayak D, Periandavan K. Homoeopathic preparation of Berberis vulgaris
as an inhibitor of calcium oxalate crystallization: An in vitro
evidence. Indian J Res Homeopathy 2015;9:152-7.
Talati J, Tiselius H, Albala DM, Ye Z. Epidemiology of stone diseases in Northern India. In: Urolithiasis: Basic Science and Clinical Practice. London: Springer; 2012.
Central Council for Research in Homoeopathy. Dossier: Science of Gentle Healing. New Delhi: Central Council for Research in Homoeopathy; 2018.
Eizayaga JE, Pozzi MI, Canan MC, Saravia L. Prevalence and likelihood ratio of symptoms in patients with good therapeutic response to Lycopodium clavatum
. A retrospective study. Homeopathy 2016;105:78-83.
Gupta AK, Gupta J, Siddiqui VA, Mishra A. A big urinary calculus expelled with homoeopathic medicine. Indian J Res Homoeopathy 2008;2:50-5. [Full text]
Sumithran PP. A case of multiple urinary calculi. Indian J Res Homoeopathy 2016;10:142-9. [Full text]
Chakma A. Renal calculi: Evidence based case study. RA J Appl Res 2015;1:227-34.
Hati AK, Rath S, Nayak C, Raj I, Sahoo AR, Paital B. Successful treatment of ureteric calculi with constitutional homoeopathic medicine Lycopodium clavatum
: A case report. J Drug Deliv Ther 2018;8:1-7.
Jyothilakshmi V, Thellamudhu G, Kumar A, Khurana A, Nayak D, Kalaiselvi P. Preliminary investigation on ultra high diluted B. vulgaris
in experimental urolithiasis. Homeopathy 2013;102:172-8.
Siddiqui VA, Singh H, Gupta J, Nayak C, Singh V, Sinha MN, et al
. A multicentre observational study to ascertain the role of homoeopathic therapy in urolithiasis. Indian J Res Homoeopath 2011;5:30-9.
World Medical Association. Declaration of Helsinki ethical principles for medical research involving human subjects. Bull World Health Organ 2001;79:373-74.
EMEA-European Medicine Agency. Guidelines for Good Clinical Practice, ICH topic E6 (R1): EMEA-European Medicine Agency; CPMP/ICH/135/95.
Dean ME, Coulter MK, Fisher P, Jobst KA, Walach H. Reporting data on homeopathic treatments (RedHot): A supplement to CONSORT. J Altern Complement Med 2007;13:19-23.
Linde K, Melchart D. Randomized controlled trials of individualized homeopathy: A state-of-the-art review. J Altern Complement Med 1998;4:371-88.
Shipley M, Berry H, Broster G, Jenkins M, Clover A, Williams I. Controlled trial of homoeopathic treatment of osteoarthritis. Lancet 1983;1:97-8.
Fisher P, Greenwood A, Huskisson EC, Turner P, Belon P. Effect of homeopathic treatment on fibrositis (primary fibromyalgia) BMJ 1989;299:365-6.
Linde K, Scholz M, Ramirez G, Clausius N, Melchart D, Jonas WB. Impact of study quality on outcome in placebo-controlled trials of homeopathy. J Clin Epidemiol 1999;52:631-6.
Gupta G. Evidence Based Pilot Study on Role of Homoeopathic Drugs in Cases of Kidney Stone, 18th
AHML, International Conference, Kuala Lumpur; 2009.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]