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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 13  |  Issue : 4  |  Page : 236-243

An open-label prospective observational trial for assessing the effect of homoeopathic medicines in patients suffering from gout


1 The Calcutta Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India
2 Independent Researcher

Date of Submission20-Jun-2019
Date of Acceptance05-Dec-2019
Date of Web Publication27-Dec-2019

Correspondence Address:
Dr. Sangita Saha
Department of Organon of Medicine and Homoeopathic Philosophy, The Calcutta Homoeopathic Medical College and Hospital, 265-266 A.P.C Road, Kolkata - 700 009, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijrh.ijrh_48_19

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  Abstract 


Background: Gout is an inflammatory arthritis associated with hyperuricaemia and intra-articular monosodium urate crystals, resulting in pain, activity limitation, disability and impact on patients' quality of life. Objective: The objective of this study was to examine the effects of individualised homoeopathic medicines in serum uric acid level and quality of life in patients suffering from gout. Methods: A prospective, single-arm, non-randomised, open-label, observational trial was conducted on 32 adults suffering from gout (diagnosed as per the American College of Rheumatology–European League Against Rheumatism gout classification criteria) at the Outpatient Department of The Calcutta Homoeopathic Medical College and Hospital, Kolkata. Serum uric acid level was the primary outcome (baseline vs. 3 months); Gout Assessment Questionnaire v2.0 (GAQ2; baseline vs. 3 months) and Measure Yourself Medical Outcome Profile v2.0 (MYMOP2; baseline, every month and up to 3 months) were the secondary outcomes. Intention-to-treat sample (n = 32) was analysed in SPSS®IBM® version 20. Results: The mean age of patients was 47.6 years; the male: female ratio was 5:3. Both serum uric acid level (mg/dl) (7.6 ± 1.4 vs. 6.0 ± 1.5; mean reduction: 1.6, 95% confidence interval [CI] = 1.1, 2.1, P < 0.001, Student's t-test) and GAQ2 total score (45.0 ± 9.1 vs. 21.0 ± 14.0; mean reduction: 24.0, 95% CI 19.1, 29.0, P < 0.001, Student's t-test) reduced significantly over 3 months. MYMOP2 scores obtained longitudinally at four different time points also revealed statistically significant reductions (P < 0.001, one-way repeated measures ANOVA). The most frequently indicated medicine was Benzoicum acidum. Conclusion: This study, though preliminary, revealed a positive treatment effect of individualised homoeopathic medicines in alleviating the symptoms of gout and improving the quality of life. More studies like randomised controlled trials with greater scientific rigour are warranted.

Keywords: American College of Rheumatology–European League against Rheumatism, Gout, Gout Assessment Questionnaire v2.0, Gout classification criteria, Homoeopathy, Measure Yourself Medical Outcome Profile v2.0


How to cite this article:
Saha S, Sarkar P, Chattopadhyay R, Saha S. An open-label prospective observational trial for assessing the effect of homoeopathic medicines in patients suffering from gout. Indian J Res Homoeopathy 2019;13:236-43

How to cite this URL:
Saha S, Sarkar P, Chattopadhyay R, Saha S. An open-label prospective observational trial for assessing the effect of homoeopathic medicines in patients suffering from gout. Indian J Res Homoeopathy [serial online] 2019 [cited 2020 Oct 29];13:236-43. Available from: https://www.ijrh.org/text.asp?2019/13/4/236/274020




  Introduction Top


Gout is an inflammatory arthritis associated with hyperuricaemia and intra-articular sodium urate crystals resulting in painful joint inflammation (arthritis). The prevalence of gout has increased substantially in the past two decades to 2.5% in the UK.[1] and 3.9% in the USA.[2] Modernisation and affluence on lifestyle, including decreased physical activity, increased consumption of foods rich in purine, fructose and alcoholic beverages and smoking, have been shown to contribute to hyperuricaemia resulting in gout,[3] and thus, developed countries tend to have a higher burden of gout than developing countries. Its incidence is 2‒6 fold higher in men than in women. The prevalence of gout in India is 0.12% as per the International League of Nations against Rheumatism, Community Oriented Program for Control of Rheumatic Diseases.[4]

The presence of monosodium urate (MSU) monohydrate crystals in a symptomatic joint/bursa (i.e. synovial fluid) or in a tophus is a sufficient criterion for the diagnosis of gout, and does not require further scoring, but its use is often restricted to secondary and tertiary care centres. Identification of MSU crystals in a primary care setting is usually not feasible as it requires both expertise in joint puncture and expensive equipment those are not readily accessible. In patients suffering from acute arthritis and in whom synovial fluid analysis is difficult, the diagnosis of gout flare should be based on certain suggestive clinical features and the serum uric acid level in a primary care setting.[5] The 2015 American College of Rheumatology–European League Against Rheumatism (ACR-EULAR gout classification criteria [6],[7] is a standardised and highly specific approach to identify relatively homogeneous group of individuals who have the clinical entity of gout in a primary care setup. The entry criterion requires the occurrence of at least 1 (one) episode of peripheral joint or bursal swelling, pain or tenderness. The domains of this criterion include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate and MSU-negative synovial fluid aspirate) and imaging (double contour sign on ultrasound or urate on dual-energy computed tomography and radiographic gout-related erosion).

PubMed search revealed total 17,736 studies on gout, of which only five used the Gout Assessment Questionnaire (GAQ) and only three studies [8],[9],[10] used Homoeopathy. However, no study result could be elucidated with GAQ2, Measure Yourself Medical Outcome Profile v2.0 (MYMOP2) and Homoeopathy. As per AYUSH Research Portal, total 21 clinical research works on gout under AYUSH system were carried out, but of those, only one was with Homoeopathy. It was a qualitative study in which ten individuals presented themselves within 5 days of the onset of acute gout and participated in a 15-day study period. Serum uric acid levels were tested on day 1 and day 6 to assess hyperuricaemia. Treatment effect was evaluated on days 1, 3 and 6 based on day subjective. This single-arm, open-label study generated some promising results in favour of Homoeopathy in treatment of acute gout within 6 days, but due to its obvious methodological shortcomings, the results can be considered as preliminary only.[11] Thus, literature on homoeopathic medicines in the treatment of gout with improvement in the quality of life remains insufficient. As the existing evidences remain miniscule, at the very first attempt, we aimed to generate some preliminary data about any possible effects of Homoeopathy in gout in pre–post comparison design, to be subjected to explanatory robust trials in future.


  Methods Top


Setting and design

A prospective, single-arm, non-randomised, open-label, observational trial was conducted from November 2017 to April 2018 on 32 adult individuals suffering from gout (as per the ACR-EULAR gout classification criteria) at the Outpatient Department of The Calcutta Homoeopathic Medical College and Hospital (CHMC and H), Kolkata. The proposed plan of work adhered to the ethical guidelines of the Declaration of Helsinki [12] and was approved by the Ethical Committee of the institution (CHMCH/IEC/13/2018, dated 05 January 2018) retrospectively. The trial could not, however, be registered with the Clinical Trials Registry of India due to a retrospective approval of the Ethical Committee. Each patient was provided with a patient information sheet in local vernacular Bengali language detailing the objectives, methods, risks and benefits of participating and confidentiality issues. Before enrolment, written informed consent was taken from the patients.

Inclusion and exclusion criteria

Individuals of either of the sexes of age 18 years and above, who had scored 8 or more in the 2015 ACR-EULAR gout classification criteria, having no unstable psychiatric illness or other systemic disease and who have not used any medication in the past 1 month were enrolled. Patients who did not give consent were excluded. Case taking was done for each patient in accordance with the standardized homoeopathic principles. Cases with manifestation of causes for secondary gout were ruled out. All the cases were diagnosed only on the basis of serum uric acid and clinical assessment. Radiological or synovial fluid examination was not done, as those were not available at the institution. Patients with score more than or equal to 8 were included, without the score of the said two examinations.

Outcome assessment

  • Primary outcome – Serum uric acid level (baseline vs. 3 months)
  • Secondary outcomes – GAQ2[13] (baseline vs. 3 months) and MYMOP2[14] (baseline, every month and up to 3 months).


All outcomes were recorded in pre-designed follow-up forms; influence of gout on health-related quality of life of patients was assessed through GAQ2 measured at baseline and at the 3rd month. GAQ2 is a disease-specific patient-reported outcome measure with 24 items, consisting of 5 different subscales: gout concern overall, gout medication side effects, well-being during attack, unmet gout treatment needs and gout concern during attack. Each item of the GAQ2 is rated 'strongly agree' to 'strongly disagree', 'all of the time' to 'none of the time' or 'not a bit' to 'extremely' on a 5-point Likert scale. A higher score denotes a greater impact of disease. It has five domains: gout concern overall, gout medication side effects, well-being during attack, unmet gout treatment needs and gout concern during attack.

Patients' responses were assessed through MYMOP2 initial and follow-up forms, measured and analysed at baseline, after the 1st, 2nd and 3rd months. The most troublesome symptom of gout in each case was recorded as Symptom 1, the intensity of which was marked by a patient on a 7-point scale (from 0 to 6, 0 = as good as it can be and 6 = as bad as it can be); simultaneously, activity, well-being of the individual and other associated symptom in each case was recorded as Symptom 2 and the intensity was scored. Patients presented with pain in heels, pain in knee, pain in toes and swelling of toe with pain as Symptom 1, and as Symptom 2, the participants presented with varied ailments like gastrointestinal complaints such as bleeding per rectum, constipation, bloated abdomen and mucoid stool; urinary complaints such as scanty urine, burning in micturition and offensive urine and sleeplessness.

Intervention and follow-up

All patients were given appropriate individualised homoeopathic medicines based on homoeopathic principles. Patients were advised to take care of their lifestyle by altering the diet and regimen. Cases were repertorized if required. Repetition was done depending on the individual requirement of the cases. Each patient enrolled was intervened for a period of 3 months, and follow-up was conducted at least once a month or earlier, as required by the patient.

Statistical analysis

Both descriptive and inferential statistics were used. Intention-to-treat sample was subjected to statistical analysis. Missing values were replaced by last value carried forward method. Student's t- test and one-way repeated measures ANOVA were used keeping P < 0.05 two-tailed as statistically significant. Statistical Package for the Social Sciences, version 20.0 (IBM Corp., IBM SPSS Statistics for Windows, Armonk, NY: USA) was used for analysis.


  Results Top


Study flow

A total of 55 patients were preliminarily screened on the basis of entry criterion of occurrence of at least one episode of peripheral joint or bursal swelling, pain or tenderness and serum uric acid level. Of which, 45 were assessed for eligibility. No patient underwent radiological examination or synovial fluid examination, as they were not available at the institution. The ACR-EULAR gout score was <8 in 9 patients and 4 did not give consent. Hence, only 32 patients could be enrolled in the study after screening them according to the inclusion and exclusion criteria [Figure 1].
Figure 1: Study flow diagram

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Baseline features

The maximum number of patients belonged to the age group of 31–40 years (n = 11; 34.4%) and 41–50 years (n = 11; 34.4%), followed by 51–60 years (n = 7; 21.9%) [Table 1]. Male patients were the majority (n = 20; 62.5%). Further, 65.6% (n = 21) of the patients had mixed type of diet, 9 patients (28.1%) had regular smoking habit, 1 patient had a habit of regular consumption of alcohol and 11 patients (34.4%) occasionally took alcohol. Dietary habit of intake of red meat regularly was presented in 9.4% (n = 3) patients, whereas 37.5% (n = 12) of the patients occasionally consumed red meat and 21 (65.6%) patients occasionally consumed soft drinks [Table 2]. The mean ACR–EULAR gout score was 8.2, with 62.5% (n = 20) having a score of 8 and 34.4% (n = 11) with score of 11. None of the patients were with score 12 and above [Table 2].
Table 1: Sociodemographic profile of the patients (n=32)

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Table 2: Eating habit and predisposing factors of the patients (n=32)

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The other comorbid conditions recorded in Symptom 2 of MYMOP2 were– gastrointestinal complaints (6 patients), haemorrhoids with bleeding per rectum (2 patients), constipation (1 patient), mucoid stool (1 patient), cough, sleeplessness in 2 patients, urinary complaints in 4 patients, scanty menses with engorgement of breast before menses in one patient and warm sensation, wet sensation, itching, burning sensation on legs, chronic intertrigo and otorrhoea in one patient each.

Symptom profile

Among the total 32 patients enrolled for the study, 2 patients presented with classical acute gout, i.e. sudden development of a painful, swollen, warm metatarsophalangeal joint, whereas 7 patients had involvement of monoarticular joint and rest of the 23 patients had polyarticular joint involvement.

Pre–post comparison

Among the 32 patients, only one patient had an increase of uric acid level after 3 months' follow-up and two dropped out of the study. The uric acid level reduced from 6.70 mg/dl to 5.48 mg/dl and 8.15 mg/dl to 6.32 mg/dl in female and male patients, respectively, after 3 months of treatment. Both serum uric acid level (mg/dl) (7.6 ± 1.4 vs. 6.0 ± 1.5; mean reduction: 1.6, 95% confidence interval [CI] = 1.1, 2.1, P < 0.001, Student's t-test) and GAQ2 total score (45.0 ± 9.1 vs. 21.0 ± 14.0; mean reduction: 24.0, 95% CI = 19.1, 29.0, P < 0.001, Student's t-test) reduced significantly over 3 months [Table 3]. The pre-medication mean score of concern of gout medication side effects reduced from 4.7 to 1.6 after 3 months of treatment, whereas the mean score of concern of well-being during attack reduced from 19.3 to 9.5 and after medication gout concern during attack reduced from 8.1 to 3.9 [Table 3]. The mean pain intensity score of MYMOP2 (Symptom 1) improved from 5.2 (baseline) to 4.3 (at the 1st month), 3.8 (at the 2nd month) and finally 3 (at the 3rd month). The mean activity score improved from 4.8 (baseline) to 3.9 (at the 1st month), 3.5 (at the 2nd month) and finally 2.7 (at the 3rd month) after medication. The mean well-being score of the patients with gout also improved from 5.1 (baseline) to 4.1 (at the 1st month), 3.5 (at the 2nd month) and finally 2.5 (at the 3rd month). A significant improvement in the mean intensity score of associated symptom in each case (recorded as Symptom 2) was changed from 3.9 at baseline to 1.6 after the 3rd month [Table 4].
Table 3: Comparison of outcome measures at baseline and after 3 months by paired t-test

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Table 4: Changes in repeatedly Measure Yourself Medical Outcome Profile v2.0 over 3 months

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Homoeopathic medicines used

As per the totality of symptoms, at the baseline, Benzoicum acidum was prescribed in 8 patients (25%) and Lachesis mutus, Lycopodium clavatum, Pulsatilla nigricans and Rhus toxicodendron were prescribed in 3 patients (9.4%) each. In the subsequent prescriptions also, Benzoicum acidum was the most frequently used medicine, followed by Colchicum autumnale. The indicated medicines were prescribed in different potencies as per the susceptibility of each individual patient and guidelines of the Organon of Medicine. Medicines were changed as per the demand of each case, when there was no such marked improvement or totality of symptoms changed. Placebo was prescribed as long as improvement continued. Among the 32 patients, no change of medicine was required for 18 patients, though repetition or prescription of higher potencies was prescribed when cases came to a standstill and the same potency was not enough to cure the case. The lists of prescribed medicines and the indications of the most frequently prescribed remedies are given in [Table 5] and [Table 6], respectively.
Table 5: Medicines prescribed during the study

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Table 6: Indications of the most frequently prescribed medicines

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  Discussion Top


Compared to baseline, serum uric acid, GAQ2 and MYMOP2 scores of participants reduced significantly over three months. As per the totality of symptoms, twenty different homoeopathic medicines were used, Benzoicum acidum being the most common.

It was observed that many associated symptoms of the patient, such as acidity, sleeplessness, bleeding per rectum, constipation, cough and itching (MYMOP2, Symptom 2), improved, suggesting Homoeopathy as a holistic care therapeutic method. This study elicited the potential effect of individualised homoeopathic medicines in not only reducing the serum uric acid but also improvement in activity and well-being of patients with gout, without any substantial medicinal adverse effects. The methodological strengths of the study were its prospective design, use of validated questionnaires, such as GAQ2 and MYMOP2, treatment by qualified and experienced homoeopathic physicians schooled in and practicing classical Homoeopathy in dealing with a challenging condition like gout – a single, simple medicine in minimum dose based on totality of symptoms in each individual case. No such published homoeopathic studies on gout could be identified to compare the findings of MYMOP2. The single published study [8] was an open-label, single-arm trial involving only ten individuals who presented within 5 days of the onset of acute gout. Three outcome measures were used – serum uric acid level, joint improvement score and Ritchie's score of joint swelling and joint tenderness – all assessed on days 1, 3 and 6. All the acute symptoms of gout were found to be resolved within a span of 6 days only. Among the used medicines, Benzoic acid, Causticum, Rhus toxicodendron, Ledum palustre, Colchicum autumnale and Calcarea carbonica were common. The findings were preliminary only and further studies were warranted. The period of study was, however less to evaluate the effect of treatment in reducing the progress of the disease and in preventing acute attacks. In the absence of control arm, there is always chance of overestimation of treatment effect sizes. In comparison, our study was better than this in terms of number of patients, use of validated questionnaires as secondary outcomes, longer duration of follow-ups and comparatively rigorous statistical analysis. Adequately powered randomised controlled trials are warranted to arrive at a definite conclusion regarding the efficacy of homoeopathic medicines in gout.


  Conclusion Top


Homoeopathic management has adequate potential in not only alleviating the serum uric acid in gout but also a significant role in improving the well-being, activity and quality of life of patients with gout, without any adverse effects. This prospective observational trial, though preliminary, revealed a positive treatment effect of homoeopathic medicines in gout. The study findings need to be interpreted with caution and further be experimented in randomised placebo-controlled design with enhanced methodological rigor and longer follow-up.

Acknowledgement

The authors would like to express their regards to Central Council for Research in Homoeopathy for giving the opportunity of carrying out this study. Deep regards to Prof. (Dr.) Satadal Das for his guidance in framing the study protocol. A sincere regards to Prof. Dr. Rakesh Singh, Dr. Rajib Purkait, Dr. Samit Dey and Dr. Debarsi Das for support. We acknowledge the Institutional Ethical Committee, all the visiting physicians, all hospital staff, patients and library staff for their co-operation that provided an opportunity to complete the study.

Financial support and sponsorship

The study was conducted as one of the projects under the Short Term Studentship in Homoeopathy (STSH) scheme of CCRH.

Conflicts of interest

None declared.



 
  References Top

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Janssens HJEM, Fransen J, Janssen M, Neogi T, Schumacher HR, Jansen TL, et al. Performance of the 2015 ACR-EULAR classification criteria for gout in a primary care population presenting with monoarthritis. Rheumatology (Oxford) 2017;56:1335-41.  Back to cited text no. 7
    
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Kluczykowska B. Effect of homeopathic remedies. Przegl Lek 1985;42:794-6.  Back to cited text no. 9
    
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ColciGel – A homeopathic colchicine gel for gout. Med Lett Drugs Ther 2016;58:5-6.  Back to cited text no. 10
    
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World Medical Association. WMA Declaration of Helsinki – Ethical principles for medical research involving human subjects. JAMA 2013;310:2191-4.  Back to cited text no. 12
    
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Hirsch JD, Lee SJ, Terkeltaub R, Khanna D, Singh J, Sarkin A, et al. Evaluation of an instrument assessing influence of Gout on health-related quality of life. J Rheumatol 2008;35:2406-14.  Back to cited text no. 13
    
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Polus BI, Kimpton AJ, Walsh MJ. Use of the measure your medical outcome profile (MYMOP2) and W-BQ12 (Well-Being) outcomes measures to evaluate chiropractic treatment: An observational study. Chiropr Man Therap 2011;19:7.  Back to cited text no. 14
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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