Clinical trial NCT01647776: Screening and Risk Factors of Colon Neoplasia
Official title: Screening and Risk Factors of Colon Neoplasia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colon Cancer
Keywords: Colon Neoplasia
Colorectal carcinoma
colon cancer
colon polyp
colonoscopy
sDNA test
FIT tests (fecal immunochemical test)
relating colon neoplasia to obesity, type 2 diabetes
colonoscopy and pathology confirmed advanced adenomas
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2012-07-24
Enrollment: 3315
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Average-risk patients undergoing colonoscopy at screening endoscopy centers in the University Hospitals of Cleveland system.

Brief summary: The investigators propose a screening population-based study to systematically evaluate the accuracy and clinical relevance of sDNA testing as a potential alternative to colonoscopy screening. In addition, the investigators propose a genetic epidemiologic study of the relation between colon polyps, an established precursor of colon cancer, and two factors that may influence risk for colon cancer: candidate genes and diet.

Detailed description: Colorectal carcinoma is currently the second most common fatal cancer in the United States, and is largely preventable through the use of screening in the asymptomatic population. Although colonoscopy is considered to be the most accurate 'gold standard' screening test, there are a significant proportion of eligible patients who decline colonoscopy or in whom colonoscopy is not readily available. More recently, testing for aberrant molecular/genetic markers in stool DNA (sDNA) is emerging as a promising alternative to colonoscopy, and some professional society guidelines have endorsed the use of sDNA testing in the early detection of colorectal cancer. However, despite some guidelines that endorse sDNA testing primarily for the detection of colorectal cancer, data on the efficacy of sDNA testing for advanced adenomas, and hence prevention of colorectal cancer, are limited.

Colon carcinogenesis is a multifactorial and multistep process that involves both genetic and environmental influences. Diet clearly plays an important role. However, despite extensive research, there has been limited success in identifying such specific dietary and nutritional factors. In particular, a number of within-population studies, including several randomized trials, have yielded conflicting results and cast serious doubt on the hypothesized central role of dietary fat and fiber in colon carcinogenesis. In contrast, there is increasing evidence relating colon neoplasia to obesity, type 2 diabetes and related metabolic abnormalities. These results, together with the marked and consistent similarities in the dietary and lifestyle risk factors for type 2 diabetes and colon neoplasia have led to the notion that insulin resistance resulting from energy imbalance (excess energy intake, physical inactivity, and obesity) may be the underlying link between these two entities. Indeed, the insulin resistance-colon neoplasia hypothesis could account for many of the dietary and lifestyle risk factors of colon neoplasia and for its high incidence in Western countries. The fact that the incidences of obesity, insulin resistance syndrome, and type 2 diabetes are escalating at epidemic pace in the Western societies makes the exploration of the insulin resistance-colon neoplasia hypothesis a subject of pressing priority.

A Food Frequency Questionnaire (FFQ), a Meat Preparation Questionnaire (MPQ), and a Physical Activity Questionnaire (PAQ), all developed at the University of Arizona Cancer Center will be used to collect dietary and physical activity data.The FFQ, MPQ and PAQ questionnaires will be self-administered by each subject according to detailed written instructions, and they are mailed to the participant with the consent forms. Subjects will be asked to donate whole blood and urine samples on the day of routine colonoscopy exams. These samples will be looked at for disease markers. Stool samples will be collected to evaluate its use at detecting colon polyps using the sDNA Test and 2 FIT tests (fecal immunochemical test).

Eligibility criteria: Inclusion Criteria:

* patients undergoing routine colonoscopy at University Hospitals, Cleveland Ohio

Exclusion Criteria:

* Unable to give written consents
* Unable to fill the questionnaires
* A history of polyps within the past 10 years (except hyperplastic polyps)
* Family history of Familial Adenomatous Polyposis (FAP) or Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
* Personal history of inflammatory bowel disease
* Personal diagnosis of any cancer, with the exception of non-melanoma skin cancer
* Any major colon surgeries (e.g. resectioning)

Primary outcomes:
measure: Stool DNA (sDNA) Feasibility and Compliance
timeFrame: within 12 weeks prior to the colonoscopy
measure: Efficacy of sDNA testing for the detection of advanced adenomas
timeFrame: prior to the colonoscopy
Secondary outcomes:
measure: Concordance/discordance between tissue and stool DNA aberrant methylation markers
timeFrame: Stool sample within 2 weeks of colonoscopy
measure: Persistence of positive sDNA testing after removal of advanced adenomas
timeFrame: at 12 months after initial colonoscopy
measure: Assess the frequency of missed or occult colonic and upper gastrointestinal neoplasia in patients with initially normal colonoscopies and persistently positive sDNA testing.
timeFrame: at 12 months after initial colonoscopy
measure: Insulin Resistance Syndrome
timeFrame: at the time of the colonoscopy
measure: Analyses stratified by ethnicity (Caucasians versus African Americans), and gender.
timeFrame: at the time of the colonoscopy
measure: Examine the impact of candidate gene variants in the insulin-GH-IGF-IRS axis on colon polyps.
timeFrame: at the time of the colonoscopy
measure: Evaluate the association of dietary patterns, glycemic index (GI) and glycemic load (GL) with colon polyps.
timeFrame: at 12 months
measure: Synthesize the information on candidate genes and diet by looking at their joint effects on colon polyps
timeFrame: at the time of the colonoscopy
measure: To investigate the association of activated (phosphorylated) IRS1, AKT and mTOR with colon adenomas.
timeFrame: at the time of the colonoscopy
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
name: Joseph E Willis, MD
role: PRINCIPAL_INVESTIGATOR
References: