Capsule Endoscopy to Screen for Small Bowel Neoplasia in Lynch Syndrome (CELSIUS)

Capsule Endoscopy in Lynch Syndrome for Small Intestinal Tumor Screening

Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary disorder characterized by a very high risk of early-onset colorectal and endometrial cancer and an increased risk of other cancers, including cancers of the stomach, ovary, urinary tract, hepatobiliary tract, pancreas and small bowel. This is a national multi-centre study evaluating the yield of small bowel screening using capsule endoscopy (CE) and double balloon enteroscopy (DBE) in Lynch syndrome subjects. The intervention consists of performing a capsule endoscopy procedure at baseline and at 2-year follow-up. In patients with polyps or malignant appearing abnormalities on capsule endoscopy, double balloon enteroscopy will be performed with subsequent endoscopic or surgical removal of neoplastic lesions. The aim of the study is to determine the prevalence and incidence of small bowel neoplasia in Lynch syndrome patients using small bowel CE and DBE.

Study Overview

• Status: Completed
• Conditions: Lynch Syndrome; Small Bowel Neoplasia
• Intervention / Treatment: Procedure: Capsule endoscopy

Detailed Description

Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominantly inherited disorder characterized by a very high risk of early-onset colorectal and endometrial cancer and an increased risk of other cancers, including cancers of the stomach, ovary, urinary tract, hepatobiliary tract, pancreas and small bowel. LS is caused by germline mutations in one of the mismatch repair (MMR) genes, mostly hMLH1, hMSH2 and hMSH6. Recently, several studies, including one from the Netherlands, have evaluated the life-time risk of small bowel cancer (SBC) in LS patients. From these studies the life-time risk of SBC is estimated around 4%. This is similar to the life-time risk of colorectal cancer in the general population, for which screening is generally advised. The risk of SBC increases with age, with an estimated prevalence of 1:500 at the age of 40, rising to an estimated prevalence of around 1:70 at the age of 60. Compared with the general population, LS patients with SBC generally present 10-20 years earlier as most patients with sporadic SBC are in their sixth or seventh decade of life. The localisation of SBC in LS is almost equal in the duodenum and jejunum, with localisation in the ileum generally occurring at a lower frequency.Until now, screening for small bowel neoplasia in Lynch syndrome patients is generally not recommended. However, the development of two new techniques to visualize the small intestine has raised the question whether screening might be useful and advisable. Small bowel capsule endoscopy (CE) has been developed as a safe, patient-friendly, minimally invasive modality for visualization of the small bowel. In addition, double-balloon enteroscopy (DBE) has been developed, a technique which allows endotherapeutic interventions. The diagnostic yields of both techniques are markedly higher than the conventional methods, such as push-enteroscopy and enteroclysis. To date, no study has been performed on screening for small bowel neoplasia in Lynch syndrome patients by means of these techniques.

The primary aim of the study is to determine the prevalence and incidence of small bowel neoplasia in Lynch syndrome patients using small bowel CE and DBE.

Secondary objectives:

The secondary aim is to identify risk factors for small bowel pathology useful in clinical practice to identify patients that might benefit from screening and to determine the additional interventional risk associated with the endoscopic procedures.

This is a national multi-centre study evaluating the yield of small bowel screening using capsule endoscopy and double balloon enteroscopy in Lynch syndrome subjects. The intervention consists of performing a capsule endoscopy procedure at baseline and at 2-year follow-up. In patients with polyps or malignant appearing abnormalities on capsule endoscopy, double balloon enteroscopy will be performed with subsequent endoscopic or surgical removal of neoplastic lesions.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Asymptomatic proven mutation carriers, with a known mutation in the hMLH1, hMSH2 or hMSH6 gene.
2. Age between 35 and 70 years.
3. Written informed consent provided.

Exclusion Criteria:

1. Subjects with a strong suspicion on a small bowel stricture.
2. Subjects with previous small bowel surgery.
3. Pregnancy.
4. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: capsule endoscopy; capsule endoscopie at baseline and after 2 years	Procedure: Capsule endoscopy; Capsule endoscopy at baseline and after 2 years; Other Names: Capsule endoscopy PillCamSB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The main outcome measure will be the number of neoplastic small bowel lesions, with determination of size, location and histological characteristics at baseline and at follow-up after 2 years.	At baseline and at 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
The secondary endpoint will be the number of complications following endoscopic procedures: rates of capsule retention and postpolypectomy bleeding and perforation.	At baseline and at 2 years

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Maastricht University Medical Center; Erasmus Medical Center; Medtronic - MITG; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); St. Antonius Hospital; The Netherlands Cancer Institute; Leiden University Medical Center; University Medical Center Nijmegen; Free University Medical Center
• Investigators: Principal Investigator: Jan J Koornstra, MD PhD, University Medical Center Groningen; Principal Investigator: Jan H Kleibeuker, MD PhD, University Medical Center Groningen; Principal Investigator: Hans F Vasen, MD PhD, Leiden University Medical Center

Publications and helpful links

General Publications

• Haanstra JF, Al-Toma A, Dekker E, Vanhoutvin SA, Nagengast FM, Mathus-Vliegen EM, van Leerdam ME, de Vos tot Nederveen Cappel WH, Sanduleanu S, Veenendaal RA, Cats A, Vasen HF, Kleibeuker JH, Koornstra JJ. Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy. Gut. 2015 Oct;64(10):1578-83. doi: 10.1136/gutjnl-2014-307348. Epub 2014 Sep 10.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: May 11, 2009
• First Submitted That Met QC Criteria: May 11, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Estimate): December 9, 2014
• Last Update Submitted That Met QC Criteria: December 8, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: HNPCC; Lynch syndrome; Capsule endoscopy; Small bowel cancer; Double balloon endoscopy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Neoplasms by Site; Disease; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Neoplasms; Syndrome; Colorectal Neoplasms, Hereditary Nonpolyposis
• Other Study ID Numbers: CELSIUS; Dutch Cancer Society 2008-4187