Capsule Endomicroscopy for Visualization of the Small Intestine in EED Population in Pakistan

This pilot study will test the feasibility and tolerability of the tethered OCT capsule and Trans Nasal Endomicroscopy probe and accessory devices for imaging the small intestine in subjects with EED and a matched non-EED cohort. This study will assess subject tolerability, optimal imaging technique, and imaging of EED features.

Study Overview

• Status: Enrolling by invitation
• Conditions: Environmental Enteric Dysfunction
• Intervention / Treatment: Device: Tethered Capsule Endomicroscope/Trans Nasal Endomicroscope

Detailed Description

Environmental enteric dysfunction (EED) is a poorly understood condition characterized by intestinal inflammation and loss of barrier function that is prevalent in regions of the world with inadequate sanitation and hygiene. EED is a major driver of malnourishment, poor neurological development, stunting, oral vaccine failure, and infection, affecting 25% of all children globally and causing over a million deaths each year . It is hypothesized that the stunting associated with EED begins in utero and that the mother's gut health has a significant impact on the fetus. Key periods of growth from pregnancy through birth and childhood offer windows for potential intervention Progress towards understanding EED and developing effective interventions has been hampered by an inability to evaluate the intestinal mucosa of populations in impoverished regions of the world where this condition is endemic.

The Tearney Laboratory has developed a minimally invasive screening method known as tethered capsule endomicroscopy (TCE) for imaging intestinal mucosa. With TCE, an unsedated subject swallows a tethered pill, which captures microscopic images of the entire esophagus, stomach, and small intestine, as it is naturally transits these organs via peristalsis and under the influence of gravity. The capsule implements a microscopic imaging technology called optical coherence tomography (OCT) that obtains 10-µm-resolution cross-sectional images of tissue. The procedure is brief, well tolerated, and can be much less expensive than endoscopy. The Investigators have implemented TCE for imaging the upper gastrointestinal tract of adults and adolescents with Celiac Disease (CD) and eosinophilic esophagitis (EoE), inflammatory conditions that are common in the US. The qualities seen thus far in their TCE studies - high imaging resolution, comprehensive tissue assessment, and minimal invasiveness - are also the qualities needed for evaluating the intestinal mucosa in populations with EED.

The Tearney Lab has also developed a new technique of deployment, Trans Nasal Endomicroscopy (TNE). The TNE catheter comprises of an introduction tube, similar to a standard Nasojejunal tube, with one or two balloons attached at the distal end. These balloons are inflated with Galinstan , a safe liquid metal alloy used in pediatric thermometers, or saline or sugar water or air which provides weight for the device to move to the duodenum under the forces of gravity and peristalsis. The TNE catheter encloses the OCT optics within, and is designed to have many of the same imaging properties of TCE but is introduced Trans nasally so that it can be effectively used in children, infants and also enable collection of various tissue samples using accessory probes for analysis through the lumen of the introduction tube.

There have been theories proposed that increased microorganism load and/or dysbiosis or an imbalance in the composition of gut microorganisms in the intestine may be important in the establishment and/or maintenance of EED. Duodenal Aspiration during endoscopy is currently used as gold standard for standard of care to collect targeted microbiome. However, the microbiome yield from this procedure is low and the procedure requires an EGD, which is a fairly invasive procedure, and carries all of the risks associated with an EGD . Tearney lab has developed a brush that can collect microbiota samples from the small intestine, in the unsedated subject in a non-invasive manner. The brush is similar to cytology brush used in standard clinical care, designed to be deployed through the TNIT tube.

The first phase of this study will test the feasibility and tolerability of the TCE device for imaging subjects with EED. The second phase of this study will test the TNE device and its accessories for imaging and microbial sample collection in pregnant women.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Karachi, Pakistan
    • Aga Khan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 18 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

The Inclusion Criteria:

• Children must be 6 months to 59 months old
• Adult subjects 18 years of age or older scheduled for a standard of care endoscopy
• EED manifesting as malnourishment (WHZ<-2) without clear etiology or healthy subjects with WHZ >=0
• Subjects and/or parents/guardians must be able to give informed consent/assent
• Subjects and/or parents/guardians must be willing to provide consent for live streaming of the procedure
• Subjects must be able to follow fasting instructions prior to the procedure

Inclusion criteria for Pregnant women:

• Subjects 18 years and older
• Subjects who are in their 2nd trimester of singleton pregnancy as confirmed by an ultrasound
• Subjects with a BMI below 18.5 without clear etiology and healthy pregnant women with BMI between 18.5 -24.5.
• Subjects must be able to follow fasting instructions prior to the procedure
• Subjects must be able to consent to the procedure

Tethered Capsule Exclusion Criteria:

• Subjects with any history of esophageal or intestinal strictures or prior GI surgery
• Subjects with history of pyloric stenosis
• Subjects with HIV diagnosis

Trans Nasal Exclusion Criteria:

• Subjects with any contraindications for NG/NJ tube placement, including but not limited to those listed below:
• Subjects with any history of esophageal or intestinal strictures or prior GI surgery
• Subjects with history of pyloric stenosis or atresia
• Subjects with suspected or diagnosed HIV, Hepatitis B and C
• Subjects with any history of esophageal or intestinal strictures or prior GI surgery
• Subjects with a history of upper gastrointestinal surgery including fundoplication
• Subjects with upper GI obstruction
• Subjects with short bowel syndrome
• Subjects with upper respiratory infection at least 7 days prior to the procedure
• 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.
• Patients on drugs which impair clotting like anticoagulants and antiplatelet drugs, NSAIDS, history of bleeding disorders.
• Subjects with upper GI bleeding

Microbiome Brush Exclusion Criteria

- Subjects with any contraindications to gastrointestinal biopsies as per standard of care

For pregnant subjects:

• Subjects with high-risk pregnancy conditions at the discretion of the subject's physician and the PI
• Pregnant subjects with a history of hyperemesis gravidarum
• Pregnant subjects with a history of severe anemia
• Pregnant subjects with gestational thrombocytopenia
• Pregnant subjects with Type 1 diabetes
• Pregnant subjects with Type 2 diabetes on medication and gestational diabetes requiring medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Feasibility of TCE; Feasibility is measured by the number of participants that we have successfully deployed the Tethered capsule device in.	Device: Tethered Capsule Endomicroscope/Trans Nasal Endomicroscope; Either the Tethered Capsule Endomicroscope or the Transnasal Endomicroscope will be deployed in the subject. Once the capsule is swallowed /TNE device is inserted, the device will naturally be moved to the duodenum via peristalsis. Once in the duodenum, imaging will be performed. For subjects receiving the TNE device, brushing samples will be collected through the introduction tube.
Experimental: Feasibility of TNE and Microbiome Brushing; Feasibility is measured by the number of participants that we have successfully deployed the TNE device and collected brush samples in.	Device: Tethered Capsule Endomicroscope/Trans Nasal Endomicroscope; Either the Tethered Capsule Endomicroscope or the Transnasal Endomicroscope will be deployed in the subject. Once the capsule is swallowed /TNE device is inserted, the device will naturally be moved to the duodenum via peristalsis. Once in the duodenum, imaging will be performed. For subjects receiving the TNE device, brushing samples will be collected through the introduction tube.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of TCE and TNE	Feasibility is measured by the number of participants that we have successfully deployed the Trans-nasal imaging device/Tethered capsule device in.	up to 3 hours during the study.

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Bill and Melinda Gates Foundation; Aga Khan University Hospital, Pakistan
• Investigators: Principal Investigator: Guillermo Tearney, M.D, PhD., Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2017
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: December 9, 2019
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Tethered Capsule Endomicroscopy; Optical Coherence Tomography; Pakistan; EED; Intestinal Disorder
• Other Study ID Numbers: 2017P001219

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes