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Screening and Risk Factors of Colon Neoplasia

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Case Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01647776
First received: July 5, 2012
Last updated: September 18, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention
Colon Cancer
Other: Stool DNA Test
Procedure: biopsies of rectal and colon mucosa
Other: Questionnaires

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Screening and Risk Factors of Colon Neoplasia

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Stool DNA (sDNA) Feasibility and Compliance [ Time Frame: within 12 weeks prior to the colonoscopy ] [ Designated as safety issue: No ]
    For this aim, we will recruit a sub-sample of the study participants to perform the sDNA test for aberrantly methylated markers in addition to their colonoscopy to assess willingness to participate, compliance with test protocol and patient satisfaction to determine potential for a larger study to evaluate the effectiveness of this test for detection of colon adenomas.

  • Efficacy of sDNA testing for the detection of advanced adenomas [ Time Frame: prior to the colonoscopy ] [ Designated as safety issue: No ]
    For the sDNA test aims, the primary goals are to assess the sensitivity and specificity of sDNA testing for the detection of advanced adenomas, and to compare the performance of the Exact sDNA Panel with that of FIT. The sensitivity and specificity of sDNA and FIT will be estimated based on the concordance and discordance of advanced adenomas detected against that of colonoscopy as the gold standard


Secondary Outcome Measures:
  • Concordance/discordance between tissue and stool DNA aberrant methylation markers [ Time Frame: Stool sample within 2 weeks of colonoscopy ] [ Designated as safety issue: No ]
    Biopsies of rectal and colon mucosa collected at the beginning of the colonoscopy for analysis of 15-PGDH pathway factors [levels of prostaglandin E2 (PG E2), and mRNA for 15-PGDH, COX-1 and COX-2 expression] as markers of risk of developing adenoma.

  • Persistence of positive sDNA testing after removal of advanced adenomas [ Time Frame: at 12 months after initial colonoscopy ] [ Designated as safety issue: No ]
    For this aim we will follow-up participants who have had positive sDNA tests and at least one advanced adenoma removed during colonoscopy. At 12 months after their initial sDNA test and colonoscopy, we will ask them to repeat the sDNA test in addition to colonoscopy recommended by their physician as standard of care.

  • Assess the frequency of missed or occult colonic and upper gastrointestinal neoplasia in patients with initially normal colonoscopies and persistently positive sDNA testing. [ Time Frame: at 12 months after initial colonoscopy ] [ Designated as safety issue: No ]
    For this aim we will follow-up participants who have had positive sDNA tests and negative colonoscopy (i.e., no adenomatous polyps observed at initial colonoscopy). At 12 months after their initial sDNA test and colonoscopy, we will ask them to repeat the sDNA test. If this second sDNA test is also positive, the participant will be offered the opportunity to have both a colonoscopy and an upper GI endoscopy (also called esophagogastroduodenoscopy or EGD)

  • Insulin Resistance Syndrome [ Time Frame: at the time of the colonoscopy ] [ Designated as safety issue: No ]
    Use latent structural equation models to fully incorporate information on the overall relations among insulin resistance syndrome pathway factors and colon polyps, including both direct and indirect effects as well as interactions between these factors.

  • Analyses stratified by ethnicity (Caucasians versus African Americans), and gender. [ Time Frame: at the time of the colonoscopy ] [ Designated as safety issue: No ]
    The analysis by ethnicity is of particular interest in sDNA testing as there is evidence that large right-sided adenomas are more prevalent among African Americans, and this ethnic population is less likely to receive screening colonoscopy as compared to Caucasians. Furthermore, the ability of sDNA and FIT for the detection of nonadvanced adenomas will be evaluated. These lesions will be defined as adenomas that are less than 1 cm in diameter and without evidence of high grade dysplasia.

  • Examine the impact of candidate gene variants in the insulin-GH-IGF-IRS axis on colon polyps. [ Time Frame: at the time of the colonoscopy ] [ Designated as safety issue: No ]
    Evaluate whether each of the following candidate gene polymorphisms and their haplotypes are linked to colon polyps: 1) Insulin; 2) Growth Hormone; 3) IGF-1; and 4) IRS-1.

  • Evaluate the association of dietary patterns, glycemic index (GI) and glycemic load (GL) with colon polyps. [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
    Conceptually, dietary patterns represent a broader picture of human diet, and thus may be more predictive of disease risk than individual foods or nutrients. In addition, there is growing evidence relating GI and/or GL to risks of obesity, type 2 diabetes as well as colon neoplasia. Therefore, we hypothesize that high dietary GL and/or GI, and/or a Western dietary pattern defined by a diverse array of dietary factors are associated with increased risk of colon polyps.

  • Synthesize the information on candidate genes and diet by looking at their joint effects on colon polyps [ Time Frame: at the time of the colonoscopy ] [ Designated as safety issue: No ]
    1) investigate their potential joint actions [i.e., gene-diet and gene-gene]; 2) use a latent structural equation modeling approach to comprehensively evaluate these factors' potential direct as well as indirect (mediated by insulin resistance syndrome) impact, on colon polyps.

  • To investigate the association of activated (phosphorylated) IRS1, AKT and mTOR with colon adenomas. [ Time Frame: at the time of the colonoscopy ] [ Designated as safety issue: No ]
    We will compare the immunohistochemistry of phosphorylated IRS1, AKT and mTOR in colon adenoma tissues with that in colon tissues from healthy control patients. Investigate the effect of obesity on the activation of the IRS1, AKT and mTOR by stratifying our cases and controls into lean and obese individuals. Evaluate the effects of serum levels of insulin, glucose, and insulin resistance index (HOMA-IR) on the activation of the IRS1, AKT and mTOR in colonic tissue.


Biospecimen Retention:   Samples With DNA

Whole Blood, Urine, Stool samples, Colon polyps


Estimated Enrollment: 1600
Study Start Date: April 2012
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Individuals without colon polyps Other: Stool DNA Test
Stool DNA test is done prior to the colonoscopy.
Other Name: sDNA
Procedure: biopsies of rectal and colon mucosa
During the standard of care colonoscopy biopsies of rectal and colon mucosa will be taken for analysis of 15-PGDH pathway factors [levels of prostaglandin E2 (PG E2), and mRNA for 15-PGDH, COX-1 and COX-2 expression] as markers of risk of developing adenoma.
Other: Questionnaires
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. Risk Factor Questionnaire (RFQ) developed by the University of Southern California will be used to collect general risk information. Stool (sDNA) test patient satisfaction survey.
Other Names:
  • Food Frequency Questionnaire (FFQ)
  • Meat Preparation Questionnaire (MPQ)
  • Physical Activity Questionnaire (PAQ)
  • Risk Factor Questionnaire (RFQ)
Individuals with colon polyps Other: Stool DNA Test
Stool DNA test is done prior to the colonoscopy.
Other Name: sDNA
Procedure: biopsies of rectal and colon mucosa
During the standard of care colonoscopy biopsies of rectal and colon mucosa will be taken for analysis of 15-PGDH pathway factors [levels of prostaglandin E2 (PG E2), and mRNA for 15-PGDH, COX-1 and COX-2 expression] as markers of risk of developing adenoma.
Other: Questionnaires
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. Risk Factor Questionnaire (RFQ) developed by the University of Southern California will be used to collect general risk information. Stool (sDNA) test patient satisfaction survey.
Other Names:
  • Food Frequency Questionnaire (FFQ)
  • Meat Preparation Questionnaire (MPQ)
  • Physical Activity Questionnaire (PAQ)
  • Risk Factor Questionnaire (RFQ)

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

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Average-risk patients undergoing colonoscopy at screening endoscopy centers in the University Hospitals of Cleveland system.

Criteria

Inclusion Criteria:

  • patients undergoing routine colonoscopy at University Hospitals, Cleveland Ohio

Exclusion Criteria:

  • Unable to give written consents
  • Unable to fill the questionnaires
  • Aged younger than 30 or older than 80
  • Unwilling to donate blood samples
  • Diagnosis of colorectal cancer or any cancer
  • Recurrent cases
  • Family history of Familial Adenomatous Polyposis (FAP) or Non-polyposis Colorectal Cancer (HNPCC).
  • History of inflammatory bowel diseases
  • Non-English Speaking
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01647776

Contacts
Contact: Todd Fennimore 216-286-4925 colonpolypstudy@case.edu

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Li Li, MD    216-368-5437    li.li@uhhospitals.org   
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Li Li, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01647776     History of Changes
Other Study ID Numbers: CASE1207, SPORE 2, 10-04-12
Study First Received: July 5, 2012
Last Updated: September 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Case Comprehensive Cancer Center:
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

Additional relevant MeSH terms:
Colonic Neoplasms
Neoplasms
Colonic Diseases
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on November 27, 2014