Feasibility of a New Diagnostic Device to Assess Small Intestinal Dysbiosis in Routine Clinical Setting.

The purpose of this study is to determine if the gas-sensing capsule can be used to identify increased numbers and a change of the composition of microbiota or microorganisms in the gut to assess small intestinal dysbiosis

Study Overview

• Status: Recruiting
• Conditions: Small Intestinal Bacterial Overgrowth
• Intervention / Treatment: Device: Atmo Gas Capsule; Procedure: Jejunal Aspiration and culture; Diagnostic test: Glucose Breath Test; Diagnostic test: Fructoolifosaccharides (FOS) Breath Test; Drug: Rifaximin; Drug: Placebo

Detailed Description

In order to diagnose an increased bacterial density in the small intestine (e.g small intestinal bacterial overgrowth) metabolic activity of the microbiota colonising the small intestine is measured by exposing these bacteria with readily fermentable carbohydrates and measure subsequently (e.g. for 2 hrs) the change of the concentration of hydrogen (H2) and/or methane in the exhaled breath that results from carbohydrate fermentation in the small intestine. This is the principle of existing breath hydrogen tests, but they are poor at distinguishing where in the intestine the H2 is being produced, and their sensitivity is diminished by 'noise' in the breath H2 as a consequence of hydrogen or methane producing bacteria in the colon and this is frequently observed in the routine clinical setting. These shortcomings can be theoretically overcome by using the Atmo Gas CapsuleR which measures after ingestion gas concentrations during gastrointestinal transit in the lumen of the gut. As a consequence at the site of fermentation parts per hundred can be measured, rather than the parts per million (ppm) when methane or hydrogen are measured in the exhaled breath. An additional advantage is that the location of the capsule is known, and therefore the source of gas production from increased bacterial load can be determined. Preliminary studies using the gas capsule have shown good correlation of patterns of breath H2 with those of regional H2 patterns generated by the gas-sensing capsule. In fact, the capsule demonstrated far greater sensitivity in measuring H2 production and a vastly superior signal-to-noise ratio in response to a fermentable load than breath testing. Hence, investigating the utility of the gas-sensing capsule as a means for 'direct' assessment of microbial density presents an opportunity to overcome the shortcomings associated with the current breath test.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Teressa Hansen, PhD; Phone Number: 07 3176 9190; Email: Teressa.Hansen@health.qld.gov.au
• Study Contact Backup: Name: Dr. Natasha Koloski; Phone Number: +61 407 126 897; Email: n.koloski@uq.edu.au

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Recruiting
      • Princess Alexandra Hospital
      • Contact: Teressa Hansen; Phone Number: 07 3176 9190; Email: Teressa.Hansen@health.qld.gov.au
      • Principal Investigator: Professor Gerald Holtmann, MD, PhD, MBA
      • Sub-Investigator: Dr. Ayesha Shah, MD, PhD
      • Sub-Investigator: Dr. Sahar Pakneshan, MD
      • Sub-Investigator: Dr. Natasha Koloski, PhD
• India
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226014,
      • Not yet recruiting
      • Sanjay Gandhi Postgraduate Institute of Medical Sciences
      • Contact: Prof Uday Ghoshal, MD; Email: udayghoshal@gmail.com
      • Contact: Shikha Sahu; Email: shikha19sss@gmail.com
      • Principal Investigator: Prof Uday Ghoshal, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients aged over 18 years presenting to the Department of Gastroenterology & Hepatology at the Princess Alexandra Hospital who require and are booked for an upper gastrointestinal endoscopy as part of the routine diagnostic work up of e.g. otherwise unexplained gastrointestinal symptoms.

Exclusion Criteria:

• Radiation Enteritis
• Pregnancy
• Gastric bezoar
• Swallowing disorders/dysphagia to food or pills
• Obese, with BMI over 35
• Suspected or known strictures of the GI tract
• Fistulas or physiological/mechanical GI obstruction
• GI surgery within the past 3 months
• Diverticultis
• Patients with implantable or portable electro-mechanical medical devices, e.g. pacemakers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary recruitment; Capsules will be ingested within 30 minutes prior to endoscopy pre- and post-antimicrobial intervention (if the patients has had a treatment) to determine if it can be used to identify increased microbial load through gas detection, and to identify responders to therapy.	Device: Atmo Gas Capsule; The Atmo gas capsule is an ingestible electronic device. This capsule consists of gas and temperature sensors, electronic circuits, radio transmitter and silver oxide batteries. It can measure the concentrations and types of intestinal gases in individuals and give an indication of gut transit time. This data is used for research purposes to gain an understanding of the microbiota's localised functionality. The data from the sensors is transmitted out of the body over the radio frequency to a handheld receiver. The capsule passes out of the human body at the end of the measurement and is disposable.; Procedure: Jejunal Aspiration and culture; Endoscopic procedure to determine microbial load of the Small bowel. This is the gold standard to determine the Active SIBO cases
Active Comparator: Active SIBO Arm - Rifaximin; If increased microbial load is determined through culture of aspiration during initial endoscopic procedure, randomised administration of Rifaximin (550g) 1 capsule twice a day for 14 days. The post-antimicrobial endoscopic procedure will be conducted at 6 weeks post the start of treatment. These hydrogen concentration results will be compared to the following conventional breath tests in a crossover study design. Immediately after the endoscopic procedure, the patient will undergo a FOS challenge recording hydrogen breath samples for 2 hours in 20 min intervals while they recover from the endoscopic procedure. A standard Glucose breath test will be performed by the patients at home not earlier that 8 hours after the endoscopic procedure.	Device: Atmo Gas Capsule; The Atmo gas capsule is an ingestible electronic device. This capsule consists of gas and temperature sensors, electronic circuits, radio transmitter and silver oxide batteries. It can measure the concentrations and types of intestinal gases in individuals and give an indication of gut transit time. This data is used for research purposes to gain an understanding of the microbiota's localised functionality. The data from the sensors is transmitted out of the body over the radio frequency to a handheld receiver. The capsule passes out of the human body at the end of the measurement and is disposable.; Procedure: Jejunal Aspiration and culture; Endoscopic procedure to determine microbial load of the Small bowel. This is the gold standard to determine the Active SIBO cases; Diagnostic test: Glucose Breath Test; Glucose is a sugar that will be broken down by bacteria if present in the small bowel with hydrogen gas as a by-product. The hydrogen produced through fermentation is measured in the patients exhaled breath; Diagnostic test: Fructoolifosaccharides (FOS) Breath Test; FOS is a long chain carbohydrate that can only be broken down by bacteria with hydrogen gas as a by-product. The hydrogen produced through fermentation is measured in the patients exhaled breath; Drug: Rifaximin; Rifaximin (550g) 1 capsule twice a day for 14 days.
Placebo Comparator: Active SIBO Arm - Placebo; If increased microbial load is determined through culture of aspiration during initial endoscopic procedure, randomised administration of placebo capsule twice a day for 14 days. The placebo will be encapsulated maize starch and pregelatinised maize starch. The post-antimicrobial endoscopic procedure will be conducted at 6 weeks post the start of treatment. These hydrogen concentration results will be compared to the following conventional breath tests in a crossover study design. Immediately after the endoscopic procedure, the patient will undergo a FOS challenge recording hydrogen breath samples for 2 hours in 20 min intervals while they recover from the endoscopic procedure. A standard Glucose breath test will be performed by the patients at home not earlier that 8 hours after the endoscopic procedure.	Device: Atmo Gas Capsule; The Atmo gas capsule is an ingestible electronic device. This capsule consists of gas and temperature sensors, electronic circuits, radio transmitter and silver oxide batteries. It can measure the concentrations and types of intestinal gases in individuals and give an indication of gut transit time. This data is used for research purposes to gain an understanding of the microbiota's localised functionality. The data from the sensors is transmitted out of the body over the radio frequency to a handheld receiver. The capsule passes out of the human body at the end of the measurement and is disposable.; Procedure: Jejunal Aspiration and culture; Endoscopic procedure to determine microbial load of the Small bowel. This is the gold standard to determine the Active SIBO cases; Diagnostic test: Glucose Breath Test; Glucose is a sugar that will be broken down by bacteria if present in the small bowel with hydrogen gas as a by-product. The hydrogen produced through fermentation is measured in the patients exhaled breath; Diagnostic test: Fructoolifosaccharides (FOS) Breath Test; FOS is a long chain carbohydrate that can only be broken down by bacteria with hydrogen gas as a by-product. The hydrogen produced through fermentation is measured in the patients exhaled breath; Drug: Placebo; randomised administration of either placebo or Rifaximin (550g) 1 capsule twice a day for 14 days. The placebo will be encapsulated maize starch and pregelatinised maize starch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Structured Assessment of Gastro-Intestinal Symptoms	22 item assessing gastrointestinal symptoms. Response items are on a 5-point scale from (1 )no problem to (5) very severe problem. This is given to patients attending the Department of Gastroenterology & Hepatology at Princess Alexandra Hospital as part of their routine clinical care.	30 minutes prior to endoscopy
Hydrogen fermentation in the small intestine as measured by the Atmo capsule	Approximately 30 minutes before the endoscopic procedure, participants will be asked to swallow the capsule (Atmo capsule), which is the size of a large vitamin pill. If the capsule still is in the stomach at the time of the procedure it will be endoscopically pushed into the small intestine. 5g of Fructooligosaccharide (FOS) in 25mL of water will be flushed via the working channel of the endoscope into the small intestine to ensure that carbohydrates are available for fermentation. Subsequently the capsule is propelled by the normal peristaltic waves through the whole gut and is excreted after several days with the faeces. During transit the capsule transmits data about the concentration of specific gases (e.g. hydrogen) in the gut to a small receiver outside of the body.	30 minutes prior to endoscopy
Small Intestine microbial load as assessed by Jejunal Aspiration and Culture	The density of the bacterial colonisation of mucosal biopsies obtained during endoscpoy will be used to determine the role of the bacterial density	During endoscpoic procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FOS Breath samples on the day of the endoscopy	Immediately prior to the endoscopy a baseline breath sample (approximately 400 cc) will be collected. FOS will be administered into the duodenum during endoscopy. After completion of the endoscopic procedure additional samples will be taken every 20 minutes up to 2 hours after the procedure.	Up to 2 hours after the endescopic procedure
Glucose Breath Test	The patients will be asked to perform (not earlier than at least 8 hours after the endoscopic procedure) at home a standard glucose test consistent with the established clinical protocol for the diagnosis of SIBO (see SOP for Hydrogen Breath Test for Small Intestinal Bacterial Overgrowth). For this test patients will drink 75 g of glucose and breath samples will be taken at baseline and every 20 minutes for 2 hrs. Samples will be analysed for increased hydrogen, methane and carbon dioxide using a Breathtracker digital microlyser (Quintron Inc USA). If bacteria are present in the upper part of the small intestine, a rise in 12ppm of hydrogen over baseline is indicative of bacterial overgrowth.	Not earlier than 12 hours after the endoscopic procedure

Collaborators and Investigators

• Sponsor: Atmo Biosciences Pty Ltd
• Investigators: Principal Investigator: Professor Gerald Holtman, MD, PhD, MBA, The University of Queensland

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: May 31, 2021
• First Posted (Actual): June 2, 2021

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Dysbiosis; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: 72853

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No