- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04302402
Multi-dimensional Clinical and Pathophysiological Profiles of Patients With Functional Dyspepsia and Effect of Gut Microbiota Manipulation Using Rifaximin for Its Treatment
Multi-dimensional Clinical and Pathophysiological Profiles of Patients With Functional Dyspepsia and Effect of Gut Microbiota Manipulation Using Rifaximin for Its Treatment: A Randomized Controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Functional dyspepsia (FD) is a common clinical syndrome characterized by the presence of recurrent or chronic upper abdominal symptoms, such as epigastric pain, early satiety, and fullness, without any structural abnormalities on the upper gastrointestinal (UGI) endoscopy. FD is a heterogeneous disorder, in which different pathophysiological mechanisms underlie specific symptom patterns. It may result from a combination of visceral hypersensitivity, gastric motor dysfunction, and low-grade mucosal inflammation. Accumulating evidence including familial aggregation recently suggested that functional gastrointestinal (GI) disorders, including FD, might be contributed by genetic factors, identification of which may improve understanding of underlying pathophysiological mechanisms. Low-grade inflammation may play an important role in the pathogenesis of FD.
H. pylori infection may contribute to FD at least in a subset of patients. According to the current Rome algorithm, H. pylori infection needs to be eradicated before the diagnosis of FD is made in spite of the fact that a large proportion of patients do not improve in spite of its eradication. In addition to H. pylori, the gut microbiota is emerging to be an important player in the pathogenesis of several GI disorders including FD. In fact, several authors suggested that small bowel microbial dysbiosis, small intestinal bacterial overgrowth, and duodenal inflammation may be responsible for symptoms of FD. One of the reasons why H. pylori eradication may not give consistent results among patients with FD might be related to the fact that variable interaction between H. pylori and gut microbiota on gastric physiology might be an important player in patients with FD. Several experts suggested that variable effect H. pylori on gastric physiology may be related to its interaction with host factors and gut microbial dysbiosis might be responsible for variable efficacy of H. pylori eradication treatment in patients with FD. The role of gut microbial dysbiosis in patients with FD is supported by a recent randomized controlled trial from Hong Kong that showed rifaximin therapy targeted towards gut microbiota was useful in the treatment of patients with FD. One of the factors that may determine symptoms of FD, particularly the sub-type called epigastric pain syndrome is hypersecretion of gastric acid. Gastritis is associated both with hypochlorhydria and hyperchlorhydria; for example, antral-predominant gastritis is associated with hyperchlorhydria and body-predominant gastritis is associated with hypochlorhydria. Pepsinogen I and II ratio is a non-invasive method to assess the topography of gastritis, such as antral or body predominant. Pepsinogen is the inactive precursor of the gastric proteolytic enzyme pepsin. Human pepsinogen comprises two isoenzymes, pepsinogen I (or A) and pepsinogen II (or C). Pepsinogen I (PG-I) is secreted mainly by chief cells of fundic mucosa, whereas pepsinogen II (PG-II) is also secreted by pyloric glands and proximal duodenal mucosa. While serum levels of PG-I correlate with levels of acid secretion, PG-II shows an inverse relationship. Therefore, the PG-I/PG-II ratio is a useful tool to evaluate gastric acid secretion, gastritis, and intestinal metaplasia. Gastrin secretion is regulated by a negative feedback mechanism looped with acid secretion. In fact, the patients with functional gastrointestinal disorders (FGIDs) were earlier thought to be psychogenic in origin; this understanding might have resulted in the development of a belief among treating physicians/gastroenterologists that these patients are rather neurotic, apprehensive individual feigning an illness. Such erroneous belief might have resulted in disservice to these patients. However, recently accumulating evidence suggests that patients with FGIDs have several pathophysiological abnormalities in the gastrointestinal (GI) tract that might not be visualized by conventional investigations such as upper GI endoscopy but are often visible with more sophisticated tests including molecular techniques. Hence, we proposed that these disorders be called micro-organic disorders. In fact, experts in Rome Foundation in the Rome IV algorithm suggested that these disorders need to be considered as disorders of "gut-brain interaction" rather than "brain-gut interaction" reinforcing the importance of the peripheral rather than central mechanisms in the pathogenesis. Rome IV also suggests that in clinical practice, a multi-dimensional clinical profile of the FGIDs (which include the categorical diagnosis, subtype, severity, psychological factors, and physiological factors including biomarkers) needs to be uncovered before further treatment of these patients. This is a paradigm shift in understanding pathogenesis and treatment of the FGIDs including FD but needs more evidence particularly from tropical and sub-tropical areas of the World. Hence, the clinical and scientific importance of the proposed study can't be over-estimated. Functional dyspepsia (FD) is an enigmatic condition that may be contributed by a variable combination of psychosocial issues like anxiety, depression, insomnia, and micro-organic issues like Helicobacter pylori infection, gastritis, duodenitis, hypersecretion of acid, degree of gastric atrophy, gastric microbiota dysbiosis. Accordingly, we aimed to study these factors among patients with FD. Rifaximin has been shown to be useful in the treatment of FD in a recent randomized control trial from Hong Kong. Since microbiota dysbiosis may be an important issue in FD, we planned to treat them with rifaximin in a randomized placebo-controlled trial and repeat the parameters such as dyspepsia score, hospital Anxiety and Depression Scale (HADS) score, Pittsburgh Sleep Quality Index (PSQI). We wish to study the pathogenetic mechanism of FD and evaluate baseline factors that may help to predict response to gut microbiota manipulation in these patients.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Uday C Ghoshal
- Phone Number: 0522 2494405
- Email: udayghoshal@gmail.com
Study Locations
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-
UP
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Lucknow, UP, India, 226014
- Department of Critical Care Medicine, SGPGIMS
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Uttar Pradesh
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Lucknow, Uttar Pradesh, India, 226014
- Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- FD diagnosis by ROME IV criteria (one or more of bothersome symptoms like postprandial fullness, early satiation, epigastric pain, and epigastric burning. It must include criteria for postprandial distress syndrome and epigastric pain syndrome for the last 3 months with symptom onset at least 6 months before diagnosis and no evidence of structural disease, including upper endoscopy).
- No organic disease on upper gastrointestinal endoscopy and ultrasound.
- Currently, not on any active therapy during the last two months.
- No previous history of Helicobacter pylori eradication.
- No antibiotic therapy within the last month.
- Not received proton pump inhibitors for a minimum of 4 weeks prior to study enrollment.
Exclusion Criteria:
- Presence of alarm symptoms such as GI bleeding, unexplained iron deficiency anemia, unintentional weight loss, palpable abdominal mass, family history of colon or stomach cancer or symptom onset ≥50 years of age and not yet screened for colon cancer, or sudden/acute onset of a new change in bowel habit)
- No proper informed consent.
- Endoscopic treatment for gastroesophageal reflux.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Rifaximin
Rifaximin 550mg thrice daily for 14 days Other Name: Normix
|
Rifaximin has been demonstrated in multiple IBS studies, through a postulated effect on the gut microbiota, to improve the symptoms of pain and bloating, which are important symptoms in subjects with functional dyspepsia
Other Names:
|
Placebo Comparator: Placebo
Placebo thrice daily for 14 days
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Similar looking placebo
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in composition of gut microbiota
Time Frame: Baseline upto 6 months
|
To study changes from baseline in composition of gut microbiota including gastric H. pylori, gastric atrophy (PG-I, PG-II ratio
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Baseline upto 6 months
|
Hospital anxiety and depression score
Time Frame: Baseline upto 6 months
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Number of items in the questionnaire reflects anxiety and depression.
Each item had been answered by the patient on a four point (0-3) response category and the possible scores ranged from 0-21 for depression (0-7 score indicates normal range, 8-10 indicates 'borderline abnormal or borderline case' and a score of 11 or higher indicates 'abnormal case'.
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Baseline upto 6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sleep quality index score
Time Frame: Baseline upto 6 months
|
Self-reported usual sleep habits for the majority of days and nights during the past month only.
The 19 self-rated and 5 non-self rated questions combined to form seven component scores, with a range of 0-21 points, "0" indicating no difficulty and "21" indicating severe difficulties.
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Baseline upto 6 months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Uday C Ghoshal, Medical council of India, Association of Indian Universities
Publications and helpful links
General Publications
- Li X, Cao Y, Wong RK, Ho KY, Wilder-Smith CH. Visceral and somatic sensory function in functional dyspepsia. Neurogastroenterol Motil. 2013 Mar;25(3):246-53, e165. doi: 10.1111/nmo.12044. Epub 2012 Nov 21.
- Sebastian-Domingo JJ. [Integrative medicine in the management of functional dyspepsia. Role of the herbal preparation STW5]. Gastroenterol Hepatol. 2014 Apr;37(4):256-61. doi: 10.1016/j.gastrohep.2013.10.001. Epub 2013 Dec 5. Spanish.
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2018-218-EMP-107
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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