Clinical trial NCT00898768: Capsule Endoscopy to Screen for Small Bowel Neoplasia in Lynch Syndrome
Official title: Capsule Endoscopy in Lynch Syndrome for Small Intestinal Tumor Screening
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Lynch Syndrome
Small Bowel Neoplasia
Keywords: Lynch syndrome
HNPCC
Capsule endoscopy
Small bowel cancer
Double balloon endoscopy
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Erasmus Medical Center
name: Leiden University Medical Center
name: St. Antonius Hospital
name: The Netherlands Cancer Institute
name: University Medical Center Nijmegen
name: Maastricht University Medical Center
name: Free University Medical Center
name: Medtronic - MITG
First posted: 2009-05-12
Enrollment: 200
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.

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.

Primary outcomes:
measure: 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.
timeFrame: At baseline and at 2 years
Secondary outcomes:
measure: The secondary endpoint will be the number of complications following endoscopic procedures: rates of capsule retention and postpolypectomy bleeding and perforation.
timeFrame: At baseline and at 2 years
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Jan J Koornstra, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: Jan H Kleibeuker, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Center
name: Hans F Vasen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.