Clinical trial NCT03434639: Fluorescence Spectroscopy for Gut Permeability Assessment
Official title: Non-invasive Transcutaneous Spectroscopy for the Assessment of Gut Permeability
Study type: OBSERVATIONAL
Overall status: UNKNOWN
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
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2018-02-15
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Blood concentration from intravenous injection
timeFrame: 1 day (study visit)
measure: Blood concentration from samples
timeFrame: 1 day (study visit)
measure: PEG permeability assay
timeFrame: 1 week (after study visit)
measure: Histology
timeFrame: 1 day (study visit)
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: IMPERIAL COLLEGE Healthcare Trust
Study officials:
affiliation: Imperial College London
name: Alex J Thompson, PhD
role: PRINCIPAL_INVESTIGATOR
References: