Fluorescence Spectroscopy for Gut Permeability Assessment

• Conditions: Inflammatory Bowel Diseases; Permeability; Increased; Liver Diseases; Development and Validation of Gut Permeability Sensor; Celiac Disease; HIV/AIDS
• Interventions: Diagnostic Test: Spectroscopic gut permeability test

• Registration Number: NCT03434639
• Lead Sponsor: Imperial College London

Brief Summary

This research aims to develop portable devices - known as fluorescence spectrometers - to monitor the leakage of fluorescent dyes out of the gut into the blood stream. These devices will measure the leakiness (permeability) of the gut in a non-invasive manner and will provide an early warning that patients are at risk of infections caused by the unwanted flow of bacteria from the intestine to the rest of the body.

Detailed Description

"Leaky gut" - or, increased permeability of the intestine - involves the leakage of certain intestinal constituents (e.g. endotoxins or even bacteria) from the gut into the rest of the body. This condition is associated with many widespread diseases including coeliac disease, inflammatory bowel disease, HIV, liver cirrhosis, sepsis and environmental enteric dysfunction (EED). It has a considerable impact on quality of life and, in extreme cases (e.g. sepsis), it can even lead to death. Furthermore, in the developing world (as part of EED), it severely hampers the mental and physical development of young children. Thus, new devices that can help us to learn more about leaky gut and more accurately monitor its effects are urgently needed.

In this project, patients will drink a small dose of a fluorescent dye. Then, by shining light on the patients' skin and recording the color and brightness of the light (fluorescence) that comes back, it will be possible to measure the amount of dye that has leaked into the blood (indicating the likelihood that bacteria are escaping from the gut and causing infections). We refer to this as a "Spectroscopic gut permeability test." We will also ask patients to take a traditional permeability test (known as a PEG permeability test) so that we can validate our new sensor. Overall, this research will deliver vital information that will improve our understanding of leaky gut and help guide the development of treatments for the many diseases in which it occurs.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-02-09
• Study First Submitted QC: 2018-02-09
• Study First Posted: 2018-02-15
• Study Start: 2019-03-29
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-10
• Last Update Posted: 2020-02-12
• Primary Completion: 2021-09-30
• Study Completion: 2021-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Ability to give informed consent
• Aged 18 years or above
• No evidence of prior adverse reactions to fluorescein, ICG, dextran or PEG
• No evidence of prior adverse reactions to iodine (for ICG experiments only)
• For healthy volunteers: healthy with no active GI/liver disease (or other condition in which increased gut permeability is expected, e.g. HIV) and no antibiotics taken within the previous four weeks.
• For cases: exhibiting symptoms of GI, liver or other diseases (e.g. HIV) in which increased intestinal permeability is expected.
• For ophthalmology patients recruited in Stage 1: healthy (i.e. as described above for healthy volunteers) and prescribed to have an ophthalmic angiography with an intravenous injection of either fluorescein or ICG.

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Exclusion Criteria

• Unable to give informed consent
• Aged <18 years
• Previous adverse reaction to fluorescein, ICG, dextran or PEG
• Known allergy to iodine (for ICG experiments only)
• Pregnancy (in Stage 1 this will be at the discretion of the patient's ophthalmologist)
• Breastfeeding (in Stage 1 this will be at the discretion of the ophthalmologist)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
3 - Increased permeability	Spectroscopic gut permeability test	Gastro-intestinal (GI) and non-GI patients who are expected to exhibit increased gut permeability (e.g. patients with celiac disease, inflammatory bowel disease (IBD), liver disease, HIV or another condition in which increased intestinal permeability is common). The more extreme cases in this group will act as positive controls.
1 - Ophthalmology patients	Spectroscopic gut permeability test	Ophthalmology patients who are receiving an intravenous dose of either fluorescein or indocyanine green (ICG) as part of their routine ophthalmic care (e.g. as part of a fluorescence angiography examination) will be recruited to the first stage of this study. These patients will take part in preliminary studies aimed at determining whether it is possible to detect fluorescein and ICG in the blood using transcutaneous fluorescence measurements.
2a - Healthy subjects	Spectroscopic gut permeability test	Healthy subjects with no known issues of increased gut permeability. These subjects will act as negative controls in all gut permeability studies.
2b - Healthy subjects (gastric emptying)	Spectroscopic gut permeability test	A subset of healthy volunteers will be recruited to take part in experiments to help in understanding the impact of gastric emptying rate as a confounding factor in measurements of gut permeability.

Primary Outcome Measures

Name	Time	Method
Blood concentration from samples	1 day (study visit)	In subjects receiving an oral dose of contrast agent, blood samples will be taken alongside the spectroscopic measurements in order to permit accurate ex vivo quantification of the serum concentration in the laboratory. These values will be compared with the spectroscopic findings.
Blood concentration from intravenous injection	1 day (study visit)	Where the blood concentration of fluorescent dye is known - for example, in ophthalmology patients who have received a direct intravenous dose of contrast agent - a direct comparison will be made between these values and the results of the spectroscopic gut permeability test without the need for further measurements.
PEG permeability assay	1 week (after study visit)	In patients who are also undergoing polyethylene glycol (PEG)-based permeability assays, spectroscopic permeability measurements will be compared to the results of this more traditional approach.
Histology	1 day (study visit)	Finally, in patients for whom intestinal biopsy and histology data is available, spectroscopic permeability measurements will be compared against histological measures of epithelial damage and permeability.

Trial Locations

Locations (1)

IMPERIAL COLLEGE Healthcare Trust; 🇬🇧 London, United Kingdom