Capsule Endoscopy to Screen for Small Bowel Neoplasia in Lynch Syndrome

NCT ID: NCT00898768

Last Updated: 2014-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2014-12-31

Brief 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.

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.

Conditions

Lynch Syndrome; Small Bowel Neoplasia

Keywords

Lynch syndrome; HNPCC; Capsule endoscopy; Small bowel cancer; Double balloon endoscopy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

capsule endoscopy

capsule endoscopie at baseline and after 2 years

Group Type: OTHER

Capsule endoscopy

Intervention Type: PROCEDURE

Capsule endoscopy at baseline and after 2 years

Interventions

Capsule endoscopy

Capsule endoscopy at baseline and after 2 years

Intervention Type: PROCEDURE

Other Intervention Names

Capsule endoscopy PillCamSB

Eligibility Criteria

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.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

St. Antonius Hospital

OTHER

Sponsor Role: collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role: collaborator

University Medical Center Nijmegen

OTHER

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: collaborator

Free University Medical Center

OTHER

Sponsor Role: collaborator

Medtronic - MITG

INDUSTRY

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Jan J Koornstra

dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jan J Koornstra, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Jan H Kleibeuker, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Hans F Vasen, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

University Medical Center Groningen

Groningen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 25209657 (View on PubMed)

Other Identifiers

Dutch Cancer Society 2008-4187

Identifier Type: -

Identifier Source: secondary_id

CELSIUS

Identifier Type: -

Identifier Source: org_study_id