Smart Pill for Measuring Gut Health in Colon Inflammation and Colon Cancer

Rationale: The gold standard diagnostic tool for inflammatory bowel disease (IBD) and colorectal carcinoma (CRC) is endoscopy, which can be burdensome for patients. The future of IBD care demands novel, minimally invasive biomarkers for personalized care and CRC screening programs could greatly benefit from new minimally invasive diagnostic tools. Oxidative stress plays a significant role in the progression of gut inflammation and colorectal cancer. Using an ingestible sensor, we aim to measure oxidation-reduction potential (ORP) directly in the gut. We hypothesize that it is feasible to measure intestinal ORP with an ingestible sensor and expect that ORP levels are elevated in patients with active ulcerative colitis (UC) and CRC before treatment, compared to after treatment.

Objective: Measurement of intestinal oxidation-reduction potential using a smart sensing ingestible and its relation to active UC and CRC.

Study design: Observational, exploratory study with invasive measurements.

Study population: 5 patients ≥ 18 years of age with UC and 5 patients ≥ 18 years of age with CRC

Main study parameters/endpoints: The main study parameter is colonic ORP profiles measured with the ingestible sensor ingestible compared before and after treatment for UC and CRC.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Risk associated with participation are deemed low. Medical or surgical treatment is not altered in any way. Patients with UC will receive an additional IUS. The GISMO GEN1 ingestible device (size 21.8 mm x 7.64 mm) is an investigational tool deemed safe for human use in clinical settings, with risks detailed in the IMDD. Device exit will be tracked via the temperature sensor of the ingestible sensor. If exit is not confirmed after 14 days, an X-ray will confirm whether the device is still in the gastrointestinal tract. If visible on the X-ray, a medical specialist will determine further action, which may include laxatives or surgery, with costs covered by the research team. If X-ray examination is necessary, the participant may experience a maximum radiation exposure of 0.10 mSv. Participant burden is low; time investment including study visits, device checks and questionnaire is estimated around 4 hours in total. Main burden is expected to be the continuous wearing of the base device as long as the ingestible sensor remains in the body.

Inclusion criteria

(For all participants:)

• Age ≥ 18 years old;
• willing and able to provide informed consent;
• defaecation pattern: generally at least one defaecation per 48 hours.

(For the UC group:)

• Diagnosis of UC confirmed by clinical, endoscopic, and/or histological evidence prior to screening as per standard criteria;
• moderately to severely active UC determined by intestinal ultrasound (bowel wall thickness (BWT) > 3 mm), starting treatment or requiring change in treatment due to non-response to their existing treatment;
• starting or optimizing treatment for colitis (including aminosalicylates, oral corticosteroids, thiopurines, biologics and small molecules).

(For the CRC group:)

• Diagnosis of non-obstructing non-locally advanced colorectal adenocarcinoma;
• ready/planned for surgery of CRC.

Exclusion criteria

(For all participants:)

• Body mass index (BMI) > 30 kg/m^2;
• known obstruction, stricture or stenosis in the gastrointestinal tract not attributable to current inflammation or tumour, potentially blocking ingestible passage. Determined as per discretion of gastroenterologist/oncologist using standard procedural clinical diagnostic or imaging techniques;
• history of complex bowel resection or recent intra-abdominal surgery (< 3 months);
• known abdominal adhesions;
• swallowing disorders, including achalasia or oropharyngeal dysfunction;
• ongoing infections;
• known to be pregnant, lactating or actively trying to get pregnant (self-reported);
• short bowel syndrome or ostomy;
• only parenteral diet;
• pacemaker or other implantable electronic devices;
• planned magnetic resonance imaging (MRI) procedure during the ingestible meaurement period;
• unwilling to undergo an X-ray examination (in the case ingestible exit cannot be confirmed);
• participation in other medical interventional/Wet medisch-wetenschappelijk onderzoek (WMO)-compliant reearch;
• participant is working (as medical personnel) in a professional healthcare facility (intensive care, emergency room, surgery rooms, clinics, patient rooms), military area (e.g. submarine, near radar installation), or heavy industrial area (e.g. power plants, automotive, mining, refineries) during the duration of the clinical investigation.

(For the CRC group:)

• Diagnosis or strong suspicion of IBD;
• planned treatment with adjuvant chemotherapy or radiotherapy.

(For the UC population:)

• Diagnosis or strong suspicion of colorectal adenocarcinoma;
• use of rectal foam/enema during the measurement period.