Fluorescence Spectroscopy for Gut Permeability Assessment

Inflammatory Bowel Diseases Clinical Trial

— GutPerm  

Official title:

Non-invasive Transcutaneous Spectroscopy for the Assessment of Gut Permeability

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03434639
• Other study ID #: 18SM4374
• Status: Recruiting
• Start date: March 29, 2019
• Est. completion date: September 30, 2021

Study information

• Verified date: February 2020
• Source: Imperial College London
• Contact: Alex J Thompson, PhD
• Phone: +442033125035
• Email: alex.thompson08[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 30, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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)

Related Conditions & MeSH terms

• Celiac Disease
• Development and Validation of Gut Permeability Sensor
• HIV/AIDS
• Inflammatory Bowel Diseases
• Liver Diseases
• Permeability; Increased

Intervention

Diagnostic Test:
• Spectroscopic gut permeability test
The spectroscopic gut permeability test first involves patients receiving an oral dose of one or more fluorescent dyes. A wearable sensor will then be attached to the patients' skin and this will be used to monitor the leakage of the fluorescent dyes from the intestine into the blood stream in a non-invasive manner. In this way, a measure of the permeability of the intestine will be obtained. Note that patients in Group 1 (ophthalmology patients) will not receive oral doses of contrast agents. Instead, the wearable sensor will simply be used to detect the presence of fluorescent dyes that were administered intravenously as part of planned ophthalmic procedures. Complete details of the spectroscopic gut permeability test can be found in the attached protocol.

Locations

Country	Name	City	State
United Kingdom	IMPERIAL COLLEGE Healthcare Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood concentration from intravenous injection	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.	1 day (study visit)
Primary	Blood concentration from samples	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.	1 day (study visit)
Primary	PEG permeability assay	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.	1 week (after study visit)
Primary	Histology	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.	1 day (study visit)