|Year : 2016 | Volume
| Issue : 3 | Page : 188-198
An open-label pilot study to explore usefulness of Homoeopathic treatment in nonerosive gastroesophageal reflux disease
Renu Mittal1, Anil Khurana1, MS Ghosh2, Ramesh Bawaskar3, Divya Taneja1, Sandhya Kashyap1, Raj K Manchanda1
1 Central Council for Research in Homoeopathy, New Delhi, India
2 Dr. Anjali Chatterjee Regional Research Institute (H), Kolkata, India
3 Regional Research Institute (H), Mumbai, India
|Date of Web Publication||11-Aug-2016|
Central Council for Research in Homoeopathy, 61-65, Institutional Area, Opposite D Block, Janak Puri, New Delhi
Source of Support: None, Conflict of Interest: None
Clinical trial registration CTRI/2014/02/004426
Background and Aim: Nonerosive gastroesophageal reflux disease or nonerosive reflux disease (NERD) is characterized by troublesome reflux-related symptoms in the absence of esophageal erosions/breaks at conventional endoscopy. There are a number of medicines cited in homoeopathic literature which can be used for treatment of symptoms such as heartburn and regurgitation. A pilot study was undertaken to explore usefulness of homoeopathic medicines in treatment of NERD. Methodology: In this study, 78 patients were screened and 34 were enrolled, having symptoms of heartburn and/or regurgitation at least twice a week, having a gastroesophageal reflux disease (GERD) symptom score of more than 4. Homoeopathic medicine was prescribed on the basis of presenting symptoms. Response to treatment was assessed on GERD symptom score, visual analog scale (VAS) for heartburn, and World Health Organization quality of life-BREF (WHO-QOL) questionnaire evaluated at baseline and at end of 8 weeks of treatment . Results: Significant difference was found in pre- and post-treatment GERD symptom score (8.79 ± 2.7 vs. 0.76 ± 1.8; P = 0.001) and VAS for heartburn (47.47 ± 19.6 vs. 5.06 ± 11.8; P = 0.001). Statistically significant improvement was seen in three domains of WHO-QOL score, i.e. psychological health, social relationship, and environmental domain. Conclusion: The findings are encouraging to open avenues for further studies on reflux disease.
Keywords: Gastroesophageal reflux disease symptom score, Homoeopathy, Nonerosive reflux disease, Quality of life
|How to cite this article:|
Mittal R, Khurana A, Ghosh M S, Bawaskar R, Taneja D, Kashyap S, Manchanda RK. An open-label pilot study to explore usefulness of Homoeopathic treatment in nonerosive gastroesophageal reflux disease. Indian J Res Homoeopathy 2016;10:188-98
|How to cite this URL:|
Mittal R, Khurana A, Ghosh M S, Bawaskar R, Taneja D, Kashyap S, Manchanda RK. An open-label pilot study to explore usefulness of Homoeopathic treatment in nonerosive gastroesophageal reflux disease. Indian J Res Homoeopathy [serial online] 2016 [cited 2017 Dec 18];10:188-98. Available from: http://www.ijrh.org/text.asp?2016/10/3/188/188240
| Introduction|| |
Heartburn and acid regurgitation are typical symptoms of reflux. Gastroesophageal reflux disease (GERD) is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications.  Nonerosive gastroesophageal reflux disease or nonerosive reflux disease (NERD) is subcategory of GERD characterized by troublesome reflux-related symptoms in the absence of esophageal erosions/breaks at conventional endoscopy and without recent acid-suppressive therapy. 
NERD accounts for 50-85% of all GERD diagnoses.  Negative endoscopic findings of NERD patients do not generally correlate with symptom severity. The main pathophysiology of NERD is incomplete gastric acid suppression, resulting in acid exposure to esophagus, greater esophageal hypersensitivity due to hyperosmotic foods, such as cake, chocolate, and alcoholic beverages which cause heartburn.  Reflux of duodenal juice in esophagus, reduced esophageal motility, and sustained secondary esophageal contractions can also be responsible. It is suggested that ingestion of hyperosmotic foods/drinks loosens the tight junctions between esophageal epithelial cells, and when gastric acid is refluxed, it easily intrudes between epithelial cells and stimulates the terminals of sensory nerves. Reflux of stomach contents is related to transient lower esophageal sphincter relaxation in these patients. 
Studies in the Asian region have shown that older age, males, family history, high socioeconomic status, increased body mass index (BMI), smoking, alcohol use, and hiatus hernia are risk factors for GERD. Three reports from South-East Asia identify that the Indian population is at higher risk for GERD.  Anxiety and depression are strongly associated with reflux symptoms.  GERD is also associated with other supraesophageal conditions such as asthma, chronic bronchitis, laryngitis, chronic cough, and atrial fibrillation. ,
The quality of life (QOL) of NERD patients is quite low.  GERD has an impact on the daily lives of affected individuals, interfering with physical activity, impairing social functioning, mental well-being, disturbing sleep, and reducing productivity at work.  NERD patients have significantly impaired QOL in both physical and mental health status as compared with normal population. It is suggested that GERD might have a more negative impact on patients with NERD than those on erosive esophagitis. 
In nonendoscoped, endoscopy-negative, or low-grade esophagitis patients, initial treatment with a proton pump inhibitor (PPI) is recommended. Step-down treatment is favored as a cost-containment measure, and the use of a half-dose PPI therapy is seen as an attractive long-term therapeutic option. NERD patients seem to have a lower response rate to PPI therapy than patients with erosive esophagitis. A systematic review combining data from seven trials found response rates, after 4 weeks of PPI treatment, of 56% in patients with erosive esophagitis and 37% in NERD patients. 
Prolong use of PPI is associated with several adverse events such as osteoporosis-related hip and spine fractures, community-acquired and nosocomial pneumonia, various enteric and nonenteric infections, and fundic gland polyps. 
In homoeopathic literature, a large number of medicines are mentioned for management of symptoms such as heartburn and regurgitation. ,,,, However, no studies have been identified in homoeopathy for treatment of NERD. As such, a pilot study was undertaken to identify usefulness of homoeopathic medicines in NERD.
| Methodology|| |
This was an open-label pilot study, conducted from September 2014 to August 2015, in accordance with the Declaration of Helsinki  on human experimentation and good clinical practice (GCP) in India. The study was approved by the Ethical Committee of the Council and was registered at clinical trial registry of India (CTRI/2014/02/004426).
Patient and Settings
This study was conducted at the outpatient departments of two research centers, namely, Regional Research Institute (H), Navi Mumbai (Maharashtra), and Dr. Anjali Chatterjee Regional Research Institute (H), Kolkata (West Bengal). The patients coming to the OPD were screened for NERD symptoms. Male and female patients between age group 18-60 years having symptoms of heartburn and/or regurgitation for 6 weeks with at least 2 episodes in a week and symptom score more than 4 on GERD symptom score scale  were enrolled in the study.
Patients with a history of gastrointestinal surgery, dysphagia, peptic ulcer, or associated alarming symptoms such as gastrointestinal hemorrhage, under any medication, suffering from systemic disease such as cardiac, pulmonary, hepatic or renal disease were excluded from the study. Pregnant or lactating females were also excluded from the study. Patients underwent investigational screening (ultrasonography-whole abdomen and pelvis, electrocardiogram, kidney function test, liver function test, stool for occult blood, absolute eosinophil count, and complete blood count) for ruling out exclusion criteria. Written informed consent was obtained from each patient before inclusion in the study.
A detailed case history was recorded in a predesigned case taking proforma. Factors associated with GERD such as alcohol consumption, smoking, body mass index (BMI), and dietary habits were also recorded. The cases were analyzed and repertorized using RADAR© Software. The medicine was selected in consultation with Materia Medica.
Esophagogastroduodenoscopy (EGD) was done in patients who agreed for the investigation to distinguish between erosive and nonerosive GERD and to assess change in EGD after treatment. However, since this was an invasive procedure, it was not mandatory for all patients to undergo the same. Findings of the EGD are reported only for cases who gave consent for investigation before the study and at the end of treatment period.
Following outcome parameters were evaluated at baseline and after 8 weeks of treatment.
Gastroesophageal reflux disease symptom score
Symptoms and effect of treatment were evaluated from patient's perspective using the validated GERD symptom score scale. , Patients were asked to describe the severity and frequency of two main symptoms, i.e. heartburn (S1) and regurgitation (S2) during previous week using a Likert scale. GERD score was calculated by multiplying the scores for severity and frequency for heartburn and regurgitation separately. The total score was obtained by adding the scores of the 2 individual symptoms (with a minimum of four to maximum of 18). On the basis of total score, the patients were categorized as mild (4-8); moderate (9-13); and severe (14-18) form of GERD. Patients were assessed for change in scores on weekly basis.
Visual analog scale (VAS) (1-100 mm) was also used for assessment of heartburn on weekly basis.
World Health Organization Quality of Life-BREF Questionnaire
QOL information was collected using the instrument World Health Organization QOL-BREF (WHO-QOL-BREF) developed by WHO.  This is a self-administered generic questionnaire with 26 questions, where two are general questions and remaining 24 encompass four domains: Physical, psychological, and social relations and environment. It emphasizes subjective responses rather than objective life conditions, with assessments made based on the preceding 2 weeks. The response options range from 1 (very dissatisfied/very poor) to 5 (very satisfied/very good). Three questions (pain and discomfort, dependence on medicinal substances, and medical treatment and negative feelings) are scored in an inverse manner. Patients were assessed for change in scores at end of 8 weeks of treatment.
Treatment and Follow-up
The indicated homoeopathic medicine was prescribed in 6C potency initially. The potency was changed as per requirements of the case and according to the homoeopathic principles.
Statistical analysis was done using Statistical Package for the Social Sciences Software (IBM SPSS 20.0 version). Mean values of GERD symptom score and VAS score were compared using repeated measure ANOVA. Change scores of QOL-BREF before and after treatment were compared using paired t-test. All values were expressed as n (%), mean ± standard deviation. P < 0.05 considered statistically significant.
| Results|| |
Since this was a pilot study, it was proposed to be conducted on a minimum sample of thirty patients. Seventy-eight patients were screened and 34 patients (22 males; 12 females) were enrolled (considering 10% drop outs). However, there were no dropouts and the data of all 34 cases are presented here [Figure 1].
Mean age group was 44.2 ± 9.9. Mean BMI was 26.1 ± 5.5 and 23 (68%) were either overweight or obese. All 34 patients suffered from heartburn. Regurgitation was seen in 32 out of 34 patients. Symptom score from 9 to 13 was observed in 38% patients while 62% had symptom score between 4 and 8 [Table 1]. Association with smoking and alcohol consumption was seen in 17.6% (6) patients only. Sleep was disturbed in 20 patients. Twenty-six percent (9) of patients had associated hepatomegaly. Most of the patients felt decrease in their working capacity due to pain and disturbance in sleep.
The patients were followed up on weekly basis for 8 weeks. The mean GERD symptom score at baseline was 8.79 ± 2.69 and at end of the treatment was reduced to 0.76 ± 1.84. The difference between score was 8.03 ± 3.04 (P = 0.001); mean change in VAS score was 42.41 ± 17.38 (P = 0.001) [Table 2]. Statistically significant changes from 2 nd week onward of treatment were seen. Comparative changes at different time points are given in [Figure 2].
Statistically significant improvement was found in QOL in three domains, i.e. psychological health, social relationship, and environmental domain. No change was seen in the domain of physical health although patients felt better in terms of their working capacity, sleep, and heartburn.
EGD was repeated in ten patients only. Four patients improved (one each of duodenitis with deformed duodenal bulb, erosive duodenitis, antral gastritis, and gastric prolapse). Five patients having gastral antritis remained static and one became worse [Table 3] and [Figure 3],[Figure 4],[Figure 5] and [Figure 6].
Lycopodium clavatum , Nux vomica, and Pulsatilla nigricans were the commonly indicated medicines [Table 4]. Seven patients were prescribed Lycopodium and all were male patients; Nux vomica was prescribed in 4 male patients, whereas Pulsatilla was prescribed in 1 male and 4 female patients. Less indicated medicines were Phosphorus (4), Cinchona officinalis (4), Arsenicum album (2), and Sepia (2).
|Table 4: Set of symptoms derived on the basis of totality of symptoms in individual cases of the indicated medicine|
Click here to view
For each drug, a symptom set has been derived based on the totality of symptoms including prescribing symptoms and other symptoms which were present but not found as the symptoms of that drug in the Synthesis repertory.
| Discussion|| |
This was a pilot study to explore the usefulness of homoeopathic medicines in treatment of NERD. The diagnosis was based on two main symptoms, i.e. heartburn and regurgitation, with GERD symptom score of more than 4. In all patients, significant decrease in the symptom score from the first follow-up assessment was seen. The improvement continued in all the cases in the GERD symptom score and the VAS scale. The changes were seen in the EGD findings as well corresponding to the symptom improvement in 10 cases.
Taking into consideration the variables known to be associated with GERD, nine cases were seen to be obese. There was no change in the obesity during the study. Seven cases reported with high anxiety as they detailed their complaints to the physician. Alcohol and smoking were associated in 17.6% cases. Although six patients said that they had reduced their smoking habits, no actual change in smoking or drinking habits was observed during the study.
A group of homoeopathic medicines has been identified for therapeutic use. All these are Polychrest medicines, and symptoms in the sphere of gastrointestinal system, sleep, and mind were most commonly used to develop the prescribing totality. The medicines prescribed on the basis of totality were associated with improvement in the patients. The findings corroborate with the holistic approach of homoeopathy bringing a general improvement which is hallmark of homoeopathic response when prescribed on totality.
The study also highlights the importance of developing a complete picture totality of the case, specifically taking into consideration mental generals, physical generals, and particular symptoms of the disease. NERD is commonly associated with chronic stress and anxiety, and the mental symptoms of the patients were identified in the same sphere.
Further, other symptoms given in the literature for the drugs have been clinically verified albeit in a small number of patients. Disturbed sleep was stated by twenty patients. It was present in all patients where Lycopodium was prescribed. Although Lycopodium is not included in the rubric "sleep disturbed" in either the Kent repertory or the Synthesis Repertory,  but Lycopodium is indicated for sleeplessness. The patients, however, reported improvement in this symptom as well. These symptoms need to be validated in a larger number of patients before they are considered as "clinical symptoms" of the drugs. Similarly, sour taste was stated by 22 patients. Researching and applying likelihood ratio will further validate the prescribing value in terms of expected clinical response.  The sample size in this study, however, was too limited to draw specific conclusions on the likelihood ratio of prescribing.
QOL assessed on WHO-QOL-BREF score showed statistically significant improvement post treatment. In individual domains, improvement was seen in psychological, social, and environmental level. The patients were more socially active, were emotionally better, and reported with increased working capacity and better sleep. No studies were found in the literature, which identify the correlation and association between the GERD score and WHO-QOL.
As per available literature, NERD is most likely associated with Helicobacter pylori infection.  Studies also show that H. pylori infection usually causes antral gastritis and is seen to be negatively associated with erosive esophagitis. Although, not an objective of this study, the EGD findings in 24 patients showed antral gastritis of mild to severe degree. This corroborates with the findings that NERD associated with antral gastritis without esophagitis is most likely due to H. pylori infection. This aspect opens further avenues for undertaking research using homoeopathic intervention on H. pylori infections.
The study has its limitation in terms of small sample size, absence of control group, and lack of laboratory evidence of improvement in all cases. EGD has not repeated in all patients as patients were not willing to go for repeat EGD which is an uncomfortable invasive procedure.
| Conclusion|| |
The study has explored the usefulness of homoeopathic medicines in treatment of NERD and helpful in improving the Quality of life of the patients. The findings are encouraging enough to open avenues for further studies to draw strong evidence on reflux disease and gastric H. pylori infections.
We are thankful to Dr. P. S. Chakraborty, Research Officer (Scientist-4), RRI (H), Kolkata, and Dr. Priyanka Nim, former SRF, CCRH, for development of protocol. The study was undertaken at RRI (H) Kolkata and RRI (H) Mumbai, under the guidance and administrative support of Dr. DB Sarkar, Assistant Director (H), and Dr. K. C. Muraleedharan, Research Officer/Scientist-4, respectively. Ms. Maya Padmanabhan Statistical Assistant conducted the data analysis.
Financial Support and Sponsorship
The financial support was provided by the Central Council for Research in Homoeopathy, New Delhi, India.
Conflicts of Interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4]