Fluorescence Spectroscopy for Gut Permeability Assessment

NCT03434639 | Unknown DMC

• 1 other identifier: 18SM4374
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Gut permeability; Fluorescence; Spectroscopy; Wearable sensor; Leaky gut

Outcome Measures

Primary Outcomes (4)

• 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)

• 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)

• 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)

• 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)

Study Arms (4)

1 - Ophthalmology patients

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.

Diagnostic Test: Spectroscopic gut permeability test

2a - Healthy subjects

Healthy subjects with no known issues of increased gut permeability. These subjects will act as negative controls in all gut permeability studies.

Diagnostic Test: Spectroscopic gut permeability test

2b - Healthy subjects (gastric emptying)

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.

Diagnostic Test: Spectroscopic gut permeability test

3 - Increased permeability

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.

Diagnostic Test: Spectroscopic gut permeability test

Interventions

Spectroscopic gut permeability test DIAGNOSTIC_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.

1 - Ophthalmology patients; 2a - Healthy subjects; 2b - Healthy subjects (gastric emptying); 3 - Increased permeability

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Potential participants will be identified and approached by members of their healthcare/clinical team. They will be identified based on their clinical condition and its potential relevance to the study - i.e. ophthalmology patients due to receive intravenous doses of fluorescein or ICG for Stage 1; GI and non-GI patients exhibiting increased intestinal permeability for Stages 2 and 3. Healthy volunteers with no indication of increased intestinal permeability will be recruited from Imperial College and St. Mary's Hospital staff. Potential healthy volunteers will be approached in person by members of the research team.

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

IMPERIAL COLLEGE Healthcare Trust

London, W2 1NY, United Kingdom

RECRUITING

Related Publications (1)

• Gan J, Chen Q, Monfort Sanchez E, Mandal N, Xu J, Wang Z, Agarwal A, Oluwatunmise E, Ramkumar P, Salam A, Chekmeneva E, Gomez-Romero M, Maslen L, Balarajah S, Perry R, Yong KK, Hoare J, Powell N, Alexander J, Avery J, Ashrafian H, Darzi A, Thompson AJ. Non-invasive fluorescence sensing reveals changes in intestinal barrier function and gastric emptying rate in a first-in-human study of Crohn's disease. Therap Adv Gastroenterol. 2025 Aug 13;18:17562848251361634. doi: 10.1177/17562848251361634. eCollection 2025.

  PMID: 40821739 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Samples of urine, blood, stool and/or intestinal tissue will be collected from certain participants. Where consent allows, remaining samples will be retained in the Imperial College BioBank after completion of the study for a total of 10 years.

MeSH Terms

Conditions

Celiac Disease; Inflammatory Bowel Diseases; Liver Diseases; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Gastroenteritis; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Alex J Thompson, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alex J Thompson, PhD

CONTACT

+442033125035; alex.thompson08@imperial.ac.uk

Ruth Nicholson

CONTACT

+442075941862; jrco@imperial.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Alex Thompson (Imperial College Research Fellow)

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: February 15, 2018
• Study Start: March 29, 2019
• Primary Completion: September 30, 2021
• Study Completion: September 30, 2021
• Last Updated: February 12, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be made available once the final results of the study have been published. Data relevant to publications will be available indefinitely through a data repository. Additional data will be held on secure servers at Imperial College London for 10 years from the completion of the study.
• Access Criteria: Data relevant to publications will be made available in an open access manner through data repositories. Additional data will be stored securely at Imperial College London for 10 years. Other researchers can request access to this data through the study chief investigator. This will be granted assuming that appropriate ethical approvals have been obtained.

Locations

GB (1)