Evaluation of Capsule Colonoscopy in Patients With Lynch Syndrome

Overview

Lynch syndrome is the most common hereditary cancer syndrome and is caused by pathogenic variants in DNA mismatch repair genes, resulting in a markedly increased lifetime risk of colorectal cancer. The estimated lifetime risk of colorectal cancer varies by the affected gene and is approximately 54-74% in men and 30-52% in women with Lynch syndrome. Colorectal cancer in this population is typically diagnosed at a younger age than in the general population. Current national guidelines recommend colonoscopic surveillance every one to two years beginning at 20-25 years of age to reduce colorectal cancer risk. However, individualized modification of surveillance strategies is under active consideration based on factors such as the specific mutated gene, family history of cancer, smoking status, prior malignancies, and age at surveillance initiation. Conventional colonoscopy, the current standard method for colorectal evaluation, may cause substantial discomfort or anxiety, leading some patients to decline participation. Colonoscopy is also resource intensive, and procedural capacity is limited. Previously reported limitations in colonoscopy resources and quality in Sweden highlight the need to evaluate alternative surveillance and screening approaches. Colon capsule endoscopy (CCE) has been available for clinical use since 2006 as a non-invasive alternative to colonoscopy, enabling endoscopic visualization of the entire colon. The system consists of a single-use, swallowable capsule containing miniature cameras that capture images as the capsule progresses through the gastrointestinal tract via natural peristalsis. Images are transmitted wirelessly to a portable data recorder worn by the patient and subsequently reviewed using dedicated software. CCE offers several advantages compared with conventional colonoscopy and CT colonography, including no requirement for sedation, endoscope insertion, gas insufflation, or ionizing radiation. The examination and image acquisition can be performed outside the hospital setting. This patient-centered approach has the potential to improve adherence to repeated examinations and long-term surveillance programs, which is particularly important for individuals with hereditary colorectal cancer syndromes. CCE may also reduce demands on healthcare resources. International guidelines indicate that the mucosal diagnostic performance of CCE is comparable to that of standard colonoscopy and that the method is appropriate for screening purposes. Adequate bowel preparation is required for both colonoscopy and CCE. Unlike conventional colonoscopy, bowel cleansing cannot be optimized during CCE, and the procedure is limited by capsule battery life, typically 10-12 hours. To maintain bowel cleanliness and facilitate capsule transit, patients administer laxative and prokinetic agents at predefined time points during the examination. The primary objective of this study is to evaluate the diagnostic performance and safety of colon capsule endoscopy as a first-line surveillance modality in patients with Lynch syndrome and to assess patient experience and acceptance of CCE compared with conventional colonoscopy.

Detailed description

Detailed Description

Study Overview This is a pragmatic, prospective, observational study designed to compare colon capsule endoscopy (CCE) with conventional colonoscopy in individuals with genetically confirmed Lynch syndrome. The study is conducted within an established colorectal cancer surveillance program and reflects routine clinical practice.

Study Objectives The primary objective of the study is to evaluate the diagnostic performance and safety of colon capsule endoscopy when used as a first-line surveillance examination in patients with genetically confirmed Lynch syndrome. Secondary objectives include assessment of patient-reported experience, acceptability, and preference for colon capsule endoscopy compared with conventional colonoscopy, assuming equivalent diagnostic performance.

Study Design and Procedures Participants undergo both colon capsule endoscopy and conventional colonoscopy using a paired, same-day, blinded design. Colon capsule endoscopy is performed using a standardized bowel preparation protocol. The capsule examination is interpreted by an experienced specialist physician.

Conventional colonoscopy, representing standard of care, is scheduled after confirmed capsule excretion on the same day without additional bowel preparation, or, if necessary, on the morning following the capsule examination. Sedation is offered according to local clinical practice. The endoscopist performing the colonoscopy is blinded to the capsule endoscopy findings.

Both examinations are evaluated, documented, and reported using predefined and standardized assessment criteria.

Blinding and Clinical Decision-Making Results from both examinations are communicated to the participant's responsible physician, who is not blinded and determines subsequent diagnostic evaluation, treatment, and continued surveillance in accordance with current clinical guidelines.

Patient-Reported Outcomes Following completion of both procedures, participants complete a structured questionnaire assessing procedural experience, perceived burden, and acceptability of colon capsule endoscopy and conventional colonoscopy. Participants are also asked to indicate their preferred examination modality if diagnostic performance is considered comparable.

Study Timeline Enrolling patients is anticipated from february 2026, with anticipated completion in December 2028.

Scientific Rationale Individuals with Lynch syndrome require lifelong colorectal surveillance beginning at a young age. Conventional colonoscopy, while effective, is invasive and resource intensive, which may affect patient adherence and healthcare capacity. Colon capsule endoscopy is a minimally invasive imaging modality that enables endoluminal visualization of the colon without the need for sedation or endoscope insertion. Evaluation of the diagnostic performance, safety, and patient acceptability of colon capsule endoscopy in this high-risk population may inform future surveillance strategies and optimize resource utilization.

Interventions

• Procedure colon capsule endoscopy
  colon capsule endoscopy

Primary outcome measures

• Diagnostic performance and safety of colon capsule endoscopy compared with conventional colonoscopy [Time frame: perioperative/periprocedural]

Secondary outcome measures (2)

• Complications associated with each examination method [Time frame: perioperative/periprocedural]
• Patient acceptability and tolerability of each examination method [Time frame: perioperative/periprocedural]

Eligibility criteria

Inclusion criteria

• Genetically confirmed Lynch syndrome with a planned surveillance colonoscopy according to guideline-based recommendations
• Age 18-60 years
• Written informed consent obtained

Exclusion criteria

• Need for an translator
• Known history of gastroparesis or intestinal pseudo-obstruction
• Known or suspected stricture or stenosis of the gastrointestinal tract
• Previous small bowel or colonic resection
• Dysphagia or swallowing difficulties
• Severe debilitating disease
• Allergy or contraindication to any medications or products used in the study
• Pregnancy or breastfeeding

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Sweden · 1 center

• Skane University Hospital Malmö — Malmö

Publications

• American Gastroenterological Association. Lynch Syndrome: AGA Patient Guideline Summary. Gastroenterology. 2015 Sep;149(3):814-5. doi: 10.1053/j.gastro.2015.07.020. Epub 2015 Jul 26. No abstract available. PMID 26219483
• Sanchez A, Roos VH, Navarro M, Pineda M, Caballol B, Moreno L, Carballal S, Rodriguez-Alonso L, Ramon Y Cajal T, Llort G, Pinol V, Lopez-Fernandez A, Salces I, Pico MD, Rivas L, Bujanda L, Garzon M, Pizarro A, Martinez de Castro E, Lopez-Arias MJ, Poves C, Garau C, Rodriguez-Alcalde D, Herraiz M, Alvarez-Urrutia C, Dacal A, Carrillo-Palau M, Cid L, Ponce M, Barreiro-Alonso E, Saperas E, Aguirre E, PMID 33157315
• Lindberg LJ, Rasmussen M, Andersen KK, Nilbert M, Therkildsen C. Benefit from extended surveillance interval on colorectal cancer risk in Lynch syndrome. Colorectal Dis. 2020 May;22(5):529-536. doi: 10.1111/codi.14926. Epub 2020 Feb 3. PMID 31860758
• Komanduri S, Dominitz JA, Rabeneck L, Kahi C, Ladabaum U, Imperiale TF, Byrne MF, Lee JK, Lieberman D, Wang AY, Sultan S, Shaukat A, Pohl H, Muthusamy VR. AGA White Paper: Challenges and Gaps in Innovation for the Performance of Colonoscopy for Screening and Surveillance of Colorectal Cancer. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2198-2209.e3. doi: 10.1016/j.cgh.2022.03.051. Epub 2022 Jun 7. PMID 35688352
• Bie AKL, Brodersen J. Why do some participants in colorectal cancer screening choose not to undergo colonoscopy following a positive test result? A qualitative study. Scand J Prim Health Care. 2018 Sep;36(3):262-271. doi: 10.1080/02813432.2018.1487520. PMID 30238859
• Kobaek-Larsen M, Kroijer R, Dyrvig AK, Buijs MM, Steele RJC, Qvist N, Baatrup G. Back-to-back colon capsule endoscopy and optical colonoscopy in colorectal cancer screening individuals. Colorectal Dis. 2018 Jun;20(6):479-485. doi: 10.1111/codi.13965. PMID 29166546
• Thygesen MK, Baatrup G, Petersen C, Qvist N, Kroijer R, Kobaek-Larsen M. Screening individuals' experiences of colonoscopy and colon capsule endoscopy; a mixed methods study. Acta Oncol. 2019;58(sup1):S71-S76. doi: 10.1080/0284186X.2019.1581372. Epub 2019 Mar 1. PMID 30821625
• Cortegoso Valdivia P, Skonieczna-Zydecka K, Elosua A, Sciberras M, Piccirelli S, Rullan M, Tabone T, Gawel K, Stachowski A, Leminski A, Marlicz W, Fernandez-Urien I, Ellul P, Spada C, Pennazio M, Toth E, Koulaouzidis A. Indications, Detection, Completion and Retention Rates of Capsule Endoscopy in Two Decades of Use: A Systematic Review and Meta-Analysis. Diagnostics (Basel). 2022 Apr 28;12(5):110 PMID 35626261

Identifiers

NCT: NCT07445828 · 2025-02563-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗