Capsule Endoscopy to Screen for Small Bowel Neoplasia in Lynch Syndrome

Lynch Syndrome Clinical Trial

— CELSIUS  

Official title:

Capsule Endoscopy in Lynch Syndrome for Small Intestinal Tumor Screening

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00898768
• Other study ID #: CELSIUS
• Secondary ID: Dutch Cancer Soc
• Status: Completed
• Phase: Phase 0
• First received: May 11, 2009
• Last updated: December 8, 2014
• Start date: May 2009
• Est. completion date: December 2014

Study information

• Verified date: December 2014
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 70 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Screening

Related Conditions & MeSH terms

• Colorectal Neoplasms, Hereditary Nonpolyposis
• Lynch Syndrome
• Neoplasms
• Small Bowel Neoplasia
• Syndrome

Intervention

Procedure:
• Capsule endoscopy
Capsule endoscopy at baseline and after 2 years

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (10)

Lead Sponsor	Collaborator
University Medical Center Groningen	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Free University Medical Center, Given Imaging Ltd., Leiden University Medical Center, Maastricht University Medical Center, St. Antonius Hospital, The Netherlands Cancer Institute, University Medical Center Nijmegen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes