Evaluation of Efficacy and Safety
of Gasex Syrup in Functional
MG Shekar kuMar*, Sr PraSad**, Sk Mitra†
*Laparoscopic Surgeon and Consultant Urologist, Shree Sai Hospitals, Choolaimedu, Chennai, India.
Executive Director, R&D Center, The Himalaya Drug Company, Bangalore, India.
Address for correspondence:
Dr SR Prasad,
R&D Center, The Himalaya Drug Company, Bangalore.
A significant reduction in the mean symptoms score of upper abdominal pain,
heartburn, abdominal bloating, belching and fullness of stomach after meals
were observed after 28 days of treatment with Gasex syrup.
bloating, belching, vomiting and in the mean symptoms score of
heartburn were included in the upper abdominal pain, heartburn,
The present study was planned study and patients having severe abdominal bloating, belching and
to evaluate the clinical efficacy and vomiting and diarrhea, and those fullness of stomach after meals
safety of Gasex syrup in functional suffering with gastric or duodenal were observed after 28 days of
dyspepsia. Dyspepsia is a symptom ulcer, cancer or varices disease treatment with Gasex syrup. There
complex of epigastric pain or were excluded from the study. were no clinically significant
discomfort believed to originate A thorough history, symptomatic adverse events, either reported
in the upper gastrointestinal evaluation and clinical examination or observed, during the entire
(GI) tract. The pathogenesis of was done for all patients before study period. Therefore, it may
functional dyspepsia remains treatment and during follow-up be concluded that Gasex syrup
uncertain. However, symptomatic visits every week till the end of is clinically safe and effective in
improvement of patients with treatment on day 28 along with the management of functional
functional dyspepsia with recording the occurrence of any dyspepsia.
current drug therapy is left adverse event/s. The predefined
with many unmet needs. This is primary end-points were rapid Introduction
because functional dyspepsia is symptomatic relief from upper Functional dyspepsia is
a heterogeneous disease and a abdominal pain, heartburn and defined as persistent or recurrent
uniform response to drug treatment bloating. The predefined secondary abdominal pain or abdominal
can therefore not be achieved. end-points were short- and long- discomfort centered in the
The present study was an open term safety, and overall compliance upper abdomen which cannot
clinical trial, conducted as per the to the drug treatment. be explained by structural or
ethical guidelines of Declaration of A total of 25 patients were biological abnormalities1,2.
Helsinki. All patients suffering from enrolled for the trial and all Discomfort refers to unpleasant
pain or discomfort centered in the patients completed the study. A sensations that the subject does
upper abdomen with associated significant reduction (p < 0.0001) not interpret as pain and may be
Indian Journal of Clinical Practice | Vol. 18 | No. 6 | Novemberber 2007 29
characterized by upper abdominal Pharmacological treatment for English, Hindi and Tamil) were
fullness, early satiety, bloating, patients with functional dyspepsia submitted to the institutional ethics
belching or nausea. It is estimated remains unsatisfactory. committee and were approved by
that the annual prevalence of Gasex syrup is a polyherbal the same.
recurrent upper abdominal formulation containing extracts The patients who attended
discomfort in the United States of Cuminum cyminum, Mentha the OPD general surgical unit of
and other Western countries is arvensis, Foeniculum vulgare, Elettaria Shree Sai Hospitals, Choolaimedu,
approximately 25%; about 2-5% of cardamomum, Apium graveolens, Chennai, India were informed
all primary care consultations are Coriandrum sativum, Curcuma longa about the study drug, its effects,
related to dyspeptic symptoms3. and Trikatu, all of which are duration of the trial, and overall
For many patients, the symptoms recommended for the management plan of the study. The patients
are of short duration or mild of dyspepsia. This study was were included in the clinical
severity4. planned to evaluate the clinical study only after written informed
Functional dyspepsia is a efficacy and safety of Gasex syrup consent was obtained from them,
highly prevalent symptom complex in the management of functional and a witness, independent of the
and a heterogenous disorder. dyspepsia. clinical trial, signed the informed
Recent studies showed potential consent form.
associations between specific Patients and methods The history was noted
pathophysiologic disturbances and by interviewing the patient.
dyspeptic symptoms. Delayed Inclusion criteria Thorough clinical examination
gastric emptying reported in about All patients aged between and symptomatic evaluation was
30% of patients with functional 18 - 55 years, suffering from pain carried out and the details were
dyspepsia is associated with centered in the upper abdomen noted down in the CRF. Patients
symptoms of postprandial fullness, with associated bloating, heartburn, were advised to take the drug at
nausea and vomiting. Impaired belching and vomiting were a dose of 2 teaspoonfuls twice a
gastric accommodation present included in the study. day after meals for 28 days.
in 40% of functional dyspepsia All patients were followed-up
patients is found to be associated Exclusion criteria every week till the end of treatment
with early satiety. Hypersensitivity Patients having severe vomiting on day 28 and symptomatic
to gastric distension is observed and diarrhea, irritable bowel evaluation and clinical examination
in 37% of functional dyspepsia syndrome, diabetes mellitus, those was done, along with recording the
patients and is associated with suffering with gastric or duodenal occurrence of any adverse event/s
symptoms of postprandial ulcer, cancer or variceal disease; (either reported or observed).
pain, belching and weight loss. and patients with history of gastric
Psychosocial factors and altered surgery or NSAIDs intake were Primary and secondary
response to duodenal lipids or excluded from the study. end-points
acid have also been identified as The predefined primary end-
pathophysiologic mechanisms. Study procedure points were rapid symptomatic
Therapeutic options are still limited The study was an open, non- relief from upper abdominal pain,
but targeted therapy directed at randomized and non-comparative, heartburn, bloating and fullness
the underlying pathophysiology prospective, phase III clinical trial, after meals. The predefined
seems desirable5. conducted at Shree Sai Hospitals, secondary end-points were short-
Symptomatic improvement of Choolaimedu, Chennai, India and long-term safety, and overall
patients with functional dyspepsia from January 2007 to March 2007, compliance to the drug treatment.
with current drug therapy is left as per the ethical guidelines of
with many unmet needs. This is Declaration of Helsinki. The study Adverse events
because functional dyspepsia is protocol, case report forms (CRFs), All adverse events, either
a heterogeneous disease and a regulatory clearance documents, reported or observed, were recorded
uniform response to drug treatment product-related information, in the CRF with information
can therefore not be achieved. and informed consent forms (in about severity, onset, duration
30 Indian Journal of Clinical Practice | Vol. 18 | No. 6 | November 2007
Table 1: Reduction in Mean Symptom Score of Upper Abdominal Pain, Heartburn, Bloating,
Belching, and Fullness after Meals with Gasex Syrup Treatment
Parameter Friedman statistic (FS)
Day 0 Day 7 Day 14 Day 21 Day 28
(symptom score) and significance
Upper abdominal 1.960 1.480 0.9600 0.8400 0.8000 FS: 68.84; p < 0.0001,
pain ± 0.1869 ± 0.1645 ± 0.1222 ± 0.1108 ± 0.1155 significant
0.8800 0.7200 0.2000 0.1200 0.0800 FS: 49.46; p < 0.0001,
± 0.2026 ± 0.1583 ± 0.0817 ± 0.0663 ± 0.0554 significant
1.640 1.440 1.000 0.7600 0.6400 FS: 57.52; p < 0.0001,
± 0.1904 ± 0.1536 ± 0.1633 ± 0.1194 ± 0.1275 significant
0.8400 0.6800 0.2400 0.1600 0.1600 FS: 55.45; p < 0.0001,
± 0.1600 ± 0.1381 ± 0.0872 ± 0.0748 ± 0.0748 significant
1.560 1.320 0.6800 0.6000 0.5600 FS: 61.90; p < 0.0001,
Fullness after meals
± 0.1833 ± 0.1497 ± 0.1381 ± 0.1291 ± 0.1013 significant
and action taken regarding the Patients were allowed to parameters from pretreatment
study drug. Relation of adverse voluntarily withdraw from the values to posttreatment values
events to the study medication study, if they experienced serious were analyzed by “Friedman’s
was predefined as “unrelated” discomfort during the study or test” followed by “Dunn’s Multiple
(a reaction that does not follow sustained serious clinical events Comparison test analysis”. The
a reasonable temporal sequence requiring specific treatment. minimum level of significance was
from the time of administration For patients withdrawing from fixed at 95% confidence limit and
of the drug), “possible” (follows the study, efforts were made to a two-sided p value of <0.05 was
a known response pattern to the ascertain the reason for dropout. considered significant.
suspected drug, but could have Non-compliance (defined as failure
been produced by the patient’s to take < 80% of the medication) Results
clinical state or other modes was not regarded as treatment
of therapy administered to the failure, and reasons for non- A total of 25 patients suffering
patient) and “probable” (follows compliance were noted. from functional dyspepsia were
a known response pattern to the included in the clinical trial and
suspected drug that could not be Statistical analysis all patients completed the study.
reasonably explained by the known Statistical analysis was done The study group had 15 male and
characteristics of the patient’s according to intention-to-treat 10 female patients. Mean age of
clinical state). principles. The changes in various the patients was 37.48 years. Brief
*p < 0.001 as compared with day 0 value *p < 0.05 as compared with day 0 value
Indian Journal of Clinical Practice | Vol. 18 | No. 6 | Novemberber 2007 31
history and clinical examination and was completely relieved by non-specific upper abdominal
showed that out of 25 patients, all day 7 itself. symptoms which cannot be
of them were suffering from upper Patient’s global assessment explained by organic or biochemical
abdominal pain and 13 patients revealed that 24% showed marked abnormalities. Functional dyspepsia
had heartburn, 21 patients had improvement, 44% had moderate is far more common than dyspepsia
bloating, 15 patients had belching, improvement and 32% had slight due to organic disease, both in the
21 patients had fullness after improvement after 28 days of community and general practice.
meals, eight had nausea and one therapy with Gasex syrup (Fig. 6). The dyspeptic symptoms are very
patient had vomiting. Investigator’s global assessment compromising and bothersome and
A significant reduction revealed that 28% of patients had result in a substantial reduction
(p < 0.0001) in mean symptoms marked improvement, 56% of of quality-of-life. The substantial
score of upper abdominal pain, them had moderate and 16% of direct and indirect medical and
heartburn, abdominal bloating, them had slight improvement at economical costs induce a high
belching and fullness of stomach the end of treatment with Gasex socioeconomic interest in the
after meals, were observed syrup (Fig. 7). pathogenesis and the treatment
after 28 days of treatment with There were no clinically options of this disease.
Gasex syrup. The reduction in significant adverse events, either Unlike peptic ulcer disease,
these symptoms started appearing reported or observed, during the where treatment is pharmacological
on the 7th day of treatment itself entire study period. and usually straightforward,
(Table 1; Fig. 1 - 5). the management of non-ulcer
Nausea and vomiting was Discussion dyspepsia (as with all functional GI
present only in eight patients Functional dyspepsia is a disorders) is more challenging and
and one patient, respectively common chronic disorder with requires a careful dialogue between
32 Indian Journal of Clinical Practice | Vol. 18 | No. 6 | November 2007
Gasex syrup. (alkaloid of peppers) have
The reduction been shown to possess diverse
in these biological activities in mammalian
s t a r t e d Peppers and ginger have been
appearing commonly used in conjunction
on 7th day in folklore medicines. Modern
of treatment research, mostly European, has
itself and documented the ability of ginger
complete relief to stimulate gastric motility
was observed (efficiency of moving food through
by 28 days. the digestive tract), to relieve
There were indigestions, and to promote
no clinically digestion. The main reason that
physician and patient. Underlying significant adverse events, either this herbal trio is part of so
pathophysiological disturbances are reported or observed, during the many Ayurvedic formulations is
not fully understood, but include entire study period. its proven ability to enhance GI
impaired gastric accommodation Earlier research works on the absorption of nutrients. Many
(upto 40% of patients), delayed extracts of individual ingredients groups of scientific investigators
gastric emptying (25-40%) and of Cuminum cyminum, Mentha attribute this bioenhancing
visceral hypersensitivity (33%). arvensis, Foeniculum vulgare, Elettaria property of pepper to its main
Pharmacological treatments cardamomum, Apium graveolens, alkaloid, piperine12.
are often disappointing and Coriandrum sativum, Curcuma longa, Mentha arvensis plant has
a significant placebo response and Trikatu were credited for antispasmodic, carminative,
(20–60%) is usually seen as in their carminative, antispasmodic, cholagogic and antimicrobial
other functional GI disorders. Most analgesic, anti-inflammatory and properties. The oil contains 95%
experts advocate a trial of proton antioxidant activities. of menthol and offers cytotoxic
pump inhibitor and/or Helicobacter Cuminum cyminum, belonging properties. The fruit of Foeniculum
pylori eradication, if present6,7. to the family Apiaceae, is widely vulgare has anti-inflammatory,
Other treatments include used in Ayurvedic medicine for the analgesic and antioxidant
prokinetic drugs (mainly cisapride, treatment of dyspepsia, diarrhea activities . Elettaria cardamomum has
subsequently withdrawn in many and jaundice8. shown gastroprotective property in
countries) and these may benefit All the herbs tested increased rats14. Extract of Apium graveolens
some. There are also limited acid secretion in the following contains apiin as the major
data suggesting benefit from declining order: Fennel, omum, constituent and exerted significant
bismuth, misoprostol, sucralfate, cardamom, cumin, coriander. anti-inflammatory property in
pirenzepine (antimuscarinic) and These herbs increased gastric acid in vivo model15. The antioxidant
antidepressants. Psychological secretion, in some by a cholinergic activity of the aqueous extracts
studies have been performed using mechanism but by other of three umbelliferous fruits -
psychotherapy, cognitive therapy mechanism(s) as well9. Cumin may coriander (Coriandrum sativum),
and hypnotherapy with reported protect the colon by decreasing cumin (Cuminum cyminum) and
improvements in dyspepsia scores. the activity of b-glucuronidase and fennel (Foeniculum vulgare) has
The present clinical study mucinase10. been demonstrated16.
observed a significant relief in “Trikatu” is an Ayurvedic Curcuma longa has been
the symptoms of dyspepsia like preparation containing black commonly used as a traditional
upper abdominal pain, heartburn, pepper, long pepper and ginger, remedy for a variety of symptoms
abdominal bloating, abdominal which is prescribed routinely such as inflammation, gastritis
belching, fullness of stomach for a variety of diseases as and gastric ulcer. When Curcuma
after meals, nausea and vomiting part of multidrug prescriptions. longa extract was administered
after 28 days of treatment with These herbs along with piperine per os to pylori-ligated rat
Indian Journal of Clinical Practice | Vol. 18 | No. 6 | Novemberber 2007 33
stomachs, it reduced gastric acid significant symptomatic relief from
secretion and protected against upper abdominal pain, heartburn,
the formation of gastric mucosal Functional dyspepsia is a abdominal bloating, belching and
lesions. Therefore, it was tested commonly encountered syndrome fullness of stomach after meals.
whether Curcuma longa extract in medical practice. Being a Symptomatic relief was evident
inhibits gastric ulcers by blocking multifactorial syndrome complex, in 14 days of study in majority
the H2 histamine receptor. These many therapeutic interventions of the patients, while almost all
findings suggest that the extract have been studied. However, were relieved within 28 days of
from Curcuma longa specifically there is no clinically effective treatment. There were no clinically
inhibits gastric acid secretion by and safe medication that can be significant adverse events, either
blocking H2 histamine receptors in recommended in the management reported or observed, during the
a competitive manner17. of functional dyspepsia. This study entire study period. Therefore,
Therefore, the observed clinical was conducted to evaluate the it may be concluded that Gasex
benefits of Gasex syrup might be clinical efficacy and safety of Gasex syrup is clinically safe and effective
due to the synergistic actions of its syrup in functional dyspepsia. in the management of functional
ingredients. This study observed a dyspepsia.
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