Clinical trial NCT04565821: Feasibility Study to Assess a Trans-nasal Intestinal Potential Difference Probe
Official title: Feasibility Study to Assess a Trans-nasal Intestinal Potential Difference Probe
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Inflammatory Disease
Permeability; Increased
Crohn Disease
Inflammatory Bowel Diseases
Environmental Enteropathy
Keywords: OCT
Optical Coherence Tomography
TNIT
Trans Nasal Introduction Tube
IPD
Intestinal Potential Difference
Leaky Gut
Gastrointestinal Permeability
GI Permeability
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2020-09-25
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DEVICE_FEASIBILITY

Brief summary: The purpose of this study is to examine the feasibility of using a trans-nasal IPD probe as a measurement tool for gut permeability

Detailed description: Increased gastrointestinal (GI) permeability is associated to several GI conditions that affect millions of people worldwide. Healthy intestinal walls limit only specific molecules to cross into the body. "Leaky gut" is a condition of unregulated and increased gut permeability that allows unwanted antigens, pathogens and microbial toxins into the bloodstream(1). This in turn leads to a subsequent immune response that includes the production of inflammatory mediators. Leaky gut is a key feature in celiac disease, Crohn's disease, inflammatory bowel disease (IBD), and environmental enteropathy and have been associated with systemic diseases including type 1 diabetes, autoimmune hepatitis, and systemic lupus erythematosus (SLE).

The current gold standard for measuring intestinal permeability is the sugar ratio test. Non-metabolized sugars of different molecular sizes are orally administered and the amount of sugar molecules absorbable across the gut lining is then quantified by measuring their relative concentrations in urine. In healthy subjects, low to none of the large-molecule disaccharides can be taken into the circulatory system, while the small-molecule monosaccharides can readily diffuse into the bloodstream. This results in low disaccharide/monosaccharide (DM) ratios for healthy subjects. Subjects with the leaky gut conditions exhibit high DM ratios in their urine. However, the sugar ratio test has low specificity, does not provide specific information on etiology, is challenging to implement when pristine urine samples cannot be collected (e.g. infants), and does not account for spatially heterogeneous disease.

An alternative approach for measuring mucosal permeability is through measuring the voltage across the intestinal wall (Intestinal potential difference; IPD) that changes with intestinal permeability. The Tearney lab has developed an IPD measuring device (IPD probe) that can be deployed trans-nasally and can measure the intestinal potential difference in real time at selected locations of the gut. The probe contains a central channel that allows us to infuse specific ionic solutions into the gut. The IPD probe also has an optical fiber inside the channel that enables the acquisition of M-mode OCT images. The M-mode OCT images make it possible to determine when the IPD probe is in contact with the tissue.

Eligibility criteria: Inclusion Criteria:

* Healthy subjects
* Subject must be 18 to 60 years of age
* Subject must be able to consent to the procedure
* Subject must fast (no solid food) for at least 8 hours prior to the procedure

Exclusion Criteria:

* Subjects with a history of upper respiratory disease or surgery
* Subjects with a history of upper gastrointestinal surgery
* Subjects with upper respiratory infection at least 7 days prior to the procedure
* Subjects with any contraindications to the placement of the NJ tube including deviated septum or any other anatomical abnormalities of the nasopharynx or upper gastrointestinal region, history of trans-sphenoidal surgery, facial or cranial trauma and fractures, chronic sinusitis, esophageal strictures, varices etc.
* Subjects with a history of or being on medications that delay gastric emptying.
* Subjects on drugs which impair clotting like anticoagulants and antiplatelet drugs, NSAIDS, history of bleeding disorders.
* Subjects using nasal steroids or any steroids for environmental allergies
* Subjects with suspected or diagnosed HIV
* Subjects with a recent use of Antibiotics within the past 4 weeks
* Subjects with a current or history of Alcoholism
* Subjects with suspected or diagnosed Hep B or Hep C
* Subjects with suspected or diagnosed Galactosemia
* Subjects enrolled in clinical trials involving interventions that affect Intestinal Permeability
* Subjects with uncontrolled Diabetes Mellitus 1 \& Diabetes Mellitus 2
* Subjects currently taking H2 Histamine Antagonists (such as Pepcid, Axid, Tagamet, Zantac, etc)
* Subjects currently taking Mast Cell stabilizers
* Subjects currently Lactating due to Pregnancy.

Primary outcomes:
measure: Baseline IPD readings
timeFrame: The outcome measure is actively recorded in real-time during the procedure, an average of 3 hours.
measure: IPD readings after Glucose/Galactose infusion
timeFrame: The outcome measure is actively recorded in real-time during the procedure, an average of 3 hours.
measure: Image Quality
timeFrame: Imaging data is collected during the procedure, and analyzed within 1 year of collection.
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Guillermo Tearney, M.D, PhD.
role: PRINCIPAL_INVESTIGATOR
References: