|Year : 2014 | Volume
| Issue : 1 | Page : 9-18
A multi-centric double blind homoeopathic pathogenetic trial of Hygrophila spinosa
G Rakshit1, AK Vichitra2, PK Chandra3, Rajpal4, Vinay Kr. Singh4, SK Choudhury1
1 Drug Proving Unit (Homoeopathy), Bhubaneswar, Odisha, India
2 Central Research Institute (Homoeopathy), Noida, Uttar Pradesh, India
3 Dr. Anjali Chatterjee Regional Research Institute (Homoeopathy), Kolkata, West Bengal, India
4 Central Council for Research in Homoeopathy, New Delhi, India
|Date of Submission||15-Jul-2013|
|Date of Acceptance||24-Feb-2014|
|Date of Web Publication||29-Mar-2014|
Officer-In-Charge, Regional Research Institute (H), Puri, Odisha - 752 001
Source of Support: None, Conflict of Interest: None
Objective: The study was conducted to elicit the pathogenetic response of Hygrophila spinosa in homoeopathic potencies on healthy human volunteers.
Methodology: The drug Hygrophila spinosa was proved by the Central Council for Research in Homoeopathy (CCRH) through randomized, double-blind, placebo-controlled method. The proving was conducted at three centres viz. Central Research Institute (H), [CRI (H)] Noida, Drug Proving Unit [DPU], Bhubaneswar and Regional Research Institute (H) [RRI (H)], Kolkata. The drug was proved in two potencies (6C and 30C) on 48 apparently healthy volunteers who were selected after conducting pre-trial medical examinations by the medical specialists and routine laboratory investigations. 32 of them where kept on interventional drug trial and remaining took placebo. At CRI (H), NOIDA, 56 dose schedule (i.e. 56 doses of drug/placebo were consumed in each batch) was followed while at DPU, Bhubaneswar and at RRI (H), Kolkata, 12 dose schedule (i.e. 12 doses of drug/placebo were to be consumed in each batch) was followed. The symptoms generated during the trial period were noted by the volunteers and elaborated by the Proving Masters which were compiled at Homoeopathic Drug Proving-cum-Data Processing cell of CCRH headquarters after decoding.
Results: Out of 32 provers who were on interventional drug trial, only 14 manifested symptoms. The drug was able to produce symptoms in both the potencies. 92 symptoms appeared during the drug trial from various locations.
Conclusion: The drug pathogenesis evolved indicates its therapeutic use for urticaria, frontal sinusitis, conjunctivitis, stomatitis, gastroenteritis, nausea (morning sickness), intermittent fever etc.
Keywords: Homoeopathy, Homoeopathic pathogenetic trial, Drug proving, Hygrophila spinosa, Pathogenetic effects
|How to cite this article:|
Rakshit G, Vichitra A K, Chandra P K, Rajpal, Singh VK, Choudhury S K. A multi-centric double blind homoeopathic pathogenetic trial of Hygrophila spinosa. Indian J Res Homoeopathy 2014;8:9-18
|How to cite this URL:|
Rakshit G, Vichitra A K, Chandra P K, Rajpal, Singh VK, Choudhury S K. A multi-centric double blind homoeopathic pathogenetic trial of Hygrophila spinosa. Indian J Res Homoeopathy [serial online] 2014 [cited 2019 Nov 13];8:9-18. Available from: http://www.ijrh.org/text.asp?2014/8/1/9/129672
| Introduction|| |
The role of traditional medicines in the treatment of various health problems is invaluable. Medicinal plants are known to provide valuable therapeutic agents, in both modern and traditional medicine. With the associated side effects of modern medicine, traditional medicines are gaining attention and are now being studied to find the scientific basis of their therapeutic actions. 
Medicinal and aromatic plants constitute a major segment of the flora, which provides raw materials for use in the pharmaceuticals, cosmetics, and drug industries. The age-old indigenous systems of medicines make use of many medicinal herbs. In one of the study of the World Health Organization, it is estimated that 80 per cent of the population of developing countries relies on traditional plant based medicines for their health requirements
Hygrophila spinosa is described in ayurvedic literature as Ikshura, Ikshugandha, and Kokilasha, which means "having eyes like Kokila or the Indian cuckoo". The medicinal value of Hygrophila spinosa can be appreciated from the fact that the plant contains terpenoids, alkaloids, flavonoids, and is traditionally known as an aphrodisiac, renal tonic and for its health-promoting properties. 
The plant has been studied for haematopoeitic, antitumor, anti-inflammatory, antipyretic, hepatoprotective, diuretic, antidiabetic, antihelmithic, antibacterial, analgesic, antimotility and antioxidant etc. The pharmacologic studies of Hygrophila spinosa indicate the immense potential of this plant in the treatment of diarrhea; inflammatory ailments, including liver and kidney disorders, as well as microbial & bacterial infections, cancer and others. The studies also indicate that the plant has an important antioxidant activity due to the presence of water-soluble compounds with potent free radical-scavenging effects. Therefore, because of all these properties of the drug, an extensive investigation on clinical efficacy of the drug is needed to explore its therapeutic utility. 
The parts of this plant are widely used in traditional medicine for the treatment of various disorders which include anasaraca, diseases of the genito-urinary tract, vesical calculi, painful micturition, dropsy from chronic renal disease, excessive thirst, flatulence, diarrhoea, dysentery, menorrhagia, leucorrhoea, gonorrhoea, asthma, blood diseases, inflammation, cancer and rheumatism. It is also experimentally proved to possess variety of pharmacologic actions which indicate its usefulness in the treatment of different types of diseases and disorders. 
It produces small red pimples and eruptions which look like measles and eruptions due to prickly heat. In some skin diseases, which are worse from heat and better from cold, its efficacy is surely found. In malarial attacks associated with urticaria it is used with great benefit. These fevers appear in the morning, there is no chill or thirst, urticaria-like eruptions come on along with the rise of temperature and there is intense itching which is relieved by cold application. It is an excellent medicine in dropsy, gonorrhoea, hepatic obstruction, rheumatism and genito-urinary affections like calculus. It has a wonderful action over insomnia; it is a sure and unfailing remedy to produce sleep.  Thus, Central Council for Research in Homoeopathy took up the systematic Homoeopathic Drug Proving of Hygrophila spinosa which has important medicinal values and benefits to elaborate its therapeutic use in Homoeopathy.
Botanical name: Hygrophila auriculata (Schum.) Heine
Synonym: Hygrophila spinosa T. Anders. Asteracantha longifolia (L.) Nees
Family : Acanthaceae
Bengali : Kuliakhara
Sanskrit : Ikshugandha, Kokilaksha
Hindi : Talimkhana
Tamil : Nirmulli, Kazhudhai Mullu
Hygrophila spinosa syn. Hygrophila auriculata (Schum.) is a herb growing in wet places. A stout herb; stems fasciculate, subquadrangular, erect, 0.6-1.5 m tall, thickened at the nodes, hispid with long hairs; with axillary spines, leaves 9X1 cm, hairy, oblanceolate, in whorls; flowers 2-3 cm long, purple-blue, bilabiate, in whorls; fruits capsule, 8 mm long, 4-8 seeded. 
The herb is common in moist places - on the banks of tanks, ditches, and paddy fields. It is believed to be indigenous to India from the Himalayas to Srilanka, Myanmar, Malaysia, and Nepal. 
To elicit the pathogenetic response of the drug Hygrophila spinosa on apparently healthy human volunteers in homoeopathic potencies.
| Material and Methods|| |
The study was a randomized, double-blind, placebo-controlled trial.
Parts used in Homoeopathy
Whole fresh plant and root 
Potencies used in the trial
6C and 30C
Participants and setting
The Homeopathic Pathogenetic trial was conducted at three centers i.e. Central Research Institute (H) [CRI (H)], Noida (Uttar Pradesh), Regional Research Institute (H) [RRI (H)], Kolkata (West Bengal) and Drug Proving Unit [DPU], Bhubaneswar (Odisha) during the year 2010-11. Total 48 apparently healthy volunteers from above mentioned three centers, between the age group 18 to 32 years, comprising 15 males and 33 females were included in the Homeopathic Pathogenetic trial. Pregnant and lactating mothers were excluded. Before enrolling the volunteers as provers, all of them were screened strictly by the experts.
'Written informed consent' from each volunteer was obtained before starting the trial. Pre-trial Medical Examination (PME) and Terminal Medical Examination (TME) of the volunteers were carried out by General Physicians, Psychiatrists, Cardiologists, Ophthalmologists, ENT Specialists, Dermatologists, Gynaecologists, Radiologists and their routine laboratory investigations at the centers to ascertain their health status. After recommendation of experts, healthy volunteers were enrolled in the Homeopathic Pathogenetic trial Programme. The sample size included 30% provers under control group at each center. So, out of 48 provers, 32 were kept on drug (verum) and 16 were on placebo (control) in all three batches i.e. placebo, 6C and 30C potency. All the provers were assigned code numbers and the coded drugs in 6C, 30C potencies and placebo were supplied in separate glass phials bearing code numbers of the respective volunteers; keeping both provers and proving masters blind. In addition a glass phial containing antidote was also kept with each batch.
Hygrophila spinosa was procured in 6C and 30C potencies in sealed bottles from licensed manufacturer of Homoeopathic medicines. Globules (number 30) were medicated with these attenuations at the Council's headquarters office and sent to Drug Proving Research Units in coded phial in 6C and 30C potency.
Placebo was made up of plain globules (number 30) moistened with plain dispensing alcohol (unsuccussed) and was therefore was indistinguishable from verum.
Methodology of Proving
The proving of Hygrophila spinosa was conducted following two different dosage schedules as per Drug Proving Protocol. 56 dose schedule  was adhered to at CRI (H), Noida while 12 dose schedule  was followed at RRI (H), Kolkata and DPU, Bhubaneswar.
The study consisted of three phases. In each phase, [56 doses at CRI Noida or 12 doses at Kolkata and Bhubnaeswar] drug or placebo were administered, divided into 4 doses per day for fourteen days or three days.
Phase-I: Placebo phase. It is useful in generating prover's response to placebo and therefore symptoms generated by the prover in this stage act as control ( intra prover) for subsequent phases.
Phase-II: In 2 nd phase, the proving was conducted with 6C potency of the drug and during this phase 30% provers consumed placebo only.
Phase-III: In 3 rd phase, the proving was conducted with 30C potency of the drug and during this phase 30% provers consumed placebo only.
Dose schedule: The provers were instructed to take 4-6 globules of a particular batch of the coded drug, four times a day, dry on tongue. Provers were instructed to note down the details of their feelings/changes in mind and body on daily basis, after taking the coded drug/placebo in 'Prover's Day Book Proforma'.
If no sign(s)/ symptoms(s) appeared, provers noted down as 'No Symptom' with date and time of intake of the respective dose of the drug/placebo.
If sign(s)/ symptoms(s) appeared, provers were asked to stop taking the coded drug as soon as he/she felt any change or any sign(s) and/or symptoms(s) developed during the trial. The prover noted down the sequence of the appearance of new sign(s) and/or symptoms(s), their progress and the number of doses after which such sign(s) and/or symptoms(s) appeared, with date, time of onset and duration for which they persisted. Any change in normal routine of the prover in respect of daily habits pertaining to diet, living conditions etc./any treatment taken were also noted in the Prover's Day Book Proforma. Intake of drug remained suspended till the sign(s) and/or symptoms(s) totally disappeared.
After disappearance of sign(s) and/or symptom(s) produced by the drug, the volunteer had to wait further for a period of 07 days before taking the remaining doses of that batch following the same dose schedule as stated above. In case of further appearance of new sign(s) and/or symptom(s), the same procedure as stated above was followed till all the 56 doses were consumed. If the prover was experiencing the same symptom(s) what he/she had already shown, he/she was asked to stop that particular batch and to switch over to the next batch after a washout period of 14 days (symptom free period between two phases of drug proving in which a volunteer does not take drug).
In case of 12 dose schedule, volunteer has to take 4 doses per day for 3 days. If symptoms appear, he/she had to stop further intake of drug from that batch and had to switch over to next batch after 30 days washout period after disappearance of symptom(s)/sign(s).
Each volunteer was interrogated by the Proving Master to verify the sign(s) and/or symptom(s) recorded by the volunteer in respect to location(s), sensation(s), modalities and concomitants, extension of symptoms, causation, clinico-pathological findings and other treatment taken, if any, in 'Symptoms Elaboration Proforma'.
During the course of trial, the volunteers were referred for specific laboratory investigations to rule out any other cause of appearance of new sign(s) and/or symptom(s). The opinion of the specialists (Honorary consultants) was also obtained, wherever needed.
After completion of trial of three phases, the provers underwent Terminal Medical Examination. On completion of all the respective phases of the pathogenetic trial programme, the compilation of data recorded in 'Prover's Day Book Proforma', 'Symptoms Elaboration Proforma', 'Pathological Report Sheets' and 'Terminal Medical Examination sheets', were made at the Council's headquarters by the Homoeopathic Drug Proving-cum-Data Processing Cell. After decoding, the sign(s) and/or symptom(s) produced by the provers kept on the interventional drug were separated from those produced by the provers kept on placebo. The sign and/or symptom, which were common to both the groups, were not taken into consideration while compiling the symptomatology of the proved verum.
Management of adverse effects
A vial of antidote was sent with each quota to each center. In this trial Camphora 6C was used as Antidote as it is believed that Camphora can antidote nearly every vegetable medicine.  The Proving Master gives antidote to the prover if symptoms continue for a long time or intensity is much to cause discomfort. Proving Master is also directed to take advice of honorary consultants and to get laboratory investigations done, if required.
Pathogenetic effects (trial symptoms) are defined as all changes in clinical events and laboratory findings reported by the volunteers during a Homoeopathic Pathogenetic Trial and recorded in the final report. The incidence of pathogenetic effects per volunteer is defined as the total number of findings observed in the trial divided by the total number of provers. 
Pathogenetic effects were deduced from:
- Comparison of symptoms developed in placebo phase with symptoms during intervention phases (intra-prover comparison)
- Comparison of symptoms developed by the provers on control (for all for phase) with provers on actual verum trial (inter-prover comparison).
| Results|| |
At Central Research Institute (H), Noida out of 18 provers, 10 provers reported symptoms. At Drug Proving Unit (H), Bhubaneswar out of 15 provers, 04 provers reported symptoms while at the same time at Regional Research Institute (H), Kolkata, out of 15 provers, none of them reported any symptom. Thus, out of 32 provers who were on interventional drug group only, 14 volunteers reported symptoms. Among these, 55 symptoms were produced during 2nd phase i.e. by 6C and 38 symptoms were produced during 3rd phase i.e. by 30C. The incidence in this Homoeopathic Drug Proving trial was 1.72 for 6C potency and 1.19 for 30C potency. In 56 dose schedule, 80 symptoms appeared as against 12 symptoms in 12 dose schedule [Table 1] and [Table 2].
| Discussion|| |
In the present Homoeopathic Pathogenetic Trial of Hygrophila spinosa, 92 symptoms appeared in 14 provers. Character of pain in various symptoms was 'burning' which can be considered as key symptom of this drug. The maximum number of symptoms were observed with 56 dose schedule and only 12 symptoms were observed with 12 dose schedule. More provers developed symptoms in 56 dose schedule. There is need to work out effective dose schedule in order to get optimum drug response.
Appearance of urticarial eruptions both at both the centres corroborated with the similar observation in small proving published in Drugs of Hindoosthan. It is quite similar to urticaria of Apis mellifica where it is better by cold application and worse from heat. More over it appeared after consuming 6C potency only and in varying doses. The drug produced intermittent type of fever with decreased thirst which has also been reported in Drugs of Hindoosthan, however there were no eruption which appeared during fever. Moreover the symptoms persisted for longer duration in 6C potency as compared to 30C potency. It can be therapeutically used for conjunctivitis on the indications of watery eyes, redness of one eye, agglutination and swelling of right eye and pain on movement of eyeballs, agg. evening. Absence of any symptoms from male and female genitalia is conspicuous. Following symptoms may also be considered as guiding symptoms:
- Diarrhoea, loose stools, non-offensive. It is accompanied with pain in lower abdomen and weakness.
- Cough with white sputum, agg. night, morning, cold drink; amel. warm thing. It is accompanied with pain in throat, decreased thirst, increased appetite, drowsiness and bodyache. Later sputum became yellowish in colour.
- Fever, intensive heat and no sweating, agg. afternoon with weakness as if someone crushed the body, desire for cold drink and weakness. Weakness increase markedly with fever and accompanied with breathlessness on movement.
- Aching pain in frontal and temporal regions of head, agg. standing; amel. pressure, lying down. It is accompanied with anxiety, drowsiness, decreased thirst.
- Diarrhea, loose offensive stool, agg. night. It is accompanied with pain in upper abdomen, amel. bending double.
| Conclusion|| |
The drug pathogenesis evolved indicates its therapeutic use for urticaria, frontal sinusitis, conjunctivitis, stomatitis, gastroenteritis, nausea (morning sickness) intermittent fever etc. However, the medicine deserves our attention in the future and more clinical experiences should be forthcoming through further clinical verification.
Authors acknowledge the contribution of Dr. Anil Khurana, Assistant Director (Hom.), Dr. Bindu Sharma, Scientist-4 and Dr. Renu Mittal Scientist-2, CCRH Hqrs. in preparing the final draft of the manuscript of the publication.
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[Table 1], [Table 2]