Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Fluorescence Spectroscopy for Gut Permeability Assessment (GutPerm)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03434639
Recruitment Status : Recruiting
First Posted : February 15, 2018
Last Update Posted : February 12, 2020
Sponsor:
Information provided by (Responsible Party):
Alexander Thompson, 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.

Condition or disease Intervention/treatment
Development and Validation of Gut Permeability Sensor Permeability; Increased Celiac Disease Inflammatory Bowel Diseases Liver Diseases HIV/AIDS Diagnostic Test: Spectroscopic gut permeability test

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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Non-invasive Transcutaneous Spectroscopy for the Assessment of Gut Permeability
Actual Study Start Date : March 29, 2019
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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

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.


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

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.


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

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.


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

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.





Primary Outcome Measures :
  1. Blood concentration from intravenous injection [ Time Frame: 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.

  2. Blood concentration from samples [ Time Frame: 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.

  3. PEG permeability assay [ Time Frame: 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.

  4. Histology [ Time Frame: 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.


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.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03434639


Contacts
Layout table for location contacts
Contact: Alex J Thompson, PhD +442033125035 alex.thompson08@imperial.ac.uk
Contact: Ruth Nicholson +442075941862 jrco@imperial.ac.uk

Locations
Layout table for location information
United Kingdom
IMPERIAL COLLEGE Healthcare Trust Recruiting
London, United Kingdom, W2 1NY
Contact: Alexander J Thompson, PhD       alex.thompson08@imperial.ac.uk   
Principal Investigator: Alexander J Thompson, PhD         
Sponsors and Collaborators
Imperial College London
Investigators
Layout table for investigator information
Principal Investigator: Alex J Thompson, PhD Imperial College London
  Study Documents (Full-Text)
Layout table for additonal information
Responsible Party: Alexander Thompson, Dr Alex Thompson (Imperial College Research Fellow), Imperial College London
ClinicalTrials.gov Identifier: NCT03434639    
Other Study ID Numbers: 18SM4374
First Posted: February 15, 2018    Key Record Dates
Last Update Posted: February 12, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized participant data will be made available to other researchers once the final results of the study have been published.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alexander Thompson, Imperial College London:
Gut permeability
Fluorescence
Spectroscopy
Wearable sensor
Leaky gut
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Diseases
Inflammatory Bowel Diseases
Celiac Disease
Digestive System Diseases
Intestinal Diseases
Gastrointestinal Diseases
Gastroenteritis
Malabsorption Syndromes
Metabolic Diseases