Colon CancerNCT01647776
Screening and Risk Factors of Colon Neoplasia
An observational study of Colon Cancer, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Colon Cancer
- What is being tested?
- Stool DNA Test, biopsies of rectal and colon mucosa and Questionnaires
- Type of treatment
- Surgery or procedure
- How many people
- 3,315 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2012to 11 Aug 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Average-risk patients undergoing colonoscopy at screening endoscopy centers in the University Hospitals of Cleveland system.
Who may be able to join
- patients undergoing routine colonoscopy at University Hospitals, Cleveland Ohio
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
About this study
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.
Read the 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).
- Conditions
- Colon Cancer
- Being tested
- Stool DNA Test, biopsies of rectal and colon mucosa, Questionnaires
- 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
- Medical subject headings
- Colonic Neoplasms, Colorectal Neoplasms, Colonic Polyps, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stool DNA TestOther
Also called sDNA
Stool DNA test is done prior to the colonoscopy.
biopsies of rectal and colon mucosaProcedure or surgery
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.
QuestionnairesOther
Also called Food Frequency Questionnaire (FFQ), Meat Preparation Questionnaire (MPQ), Physical Activity Questionnaire (PAQ), Risk Factor Questionnaire (RFQ)
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.
| Study group | Role | What they receive |
|---|---|---|
| Individuals without colon polyps | Not described Receives: Other: Stool DNA Test; Procedure: biopsies of rectal and colon mucosa; Other: Questionnaires | |
| Individuals with colon polyps | Not described Receives: Other: Stool DNA Test; Procedure: biopsies of rectal and colon mucosa; Other: Questionnaires |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stool DNA (sDNA) Feasibility and Compliance
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.
Measured: within 12 weeks prior to the colonoscopy
Efficacy of sDNA testing for the detection of advanced adenomas
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
Measured: prior to the colonoscopy
Secondary outcomes (9)
Concordance/discordance between tissue and stool DNA aberrant methylation markers
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.
Measured: Stool sample within 2 weeks of colonoscopy
Persistence of positive sDNA testing after removal of advanced adenomas
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.
Measured: at 12 months after initial colonoscopy
Assess the frequency of missed or occult colonic and upper gastrointestinal neoplasia in patients with initially normal colonoscopies and persistently positive sDNA testing.
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)
Measured: at 12 months after initial colonoscopy
Insulin Resistance Syndrome
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.
Measured: at the time of the colonoscopy
Analyses stratified by ethnicity (Caucasians versus African Americans), and gender.
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.
Measured: at the time of the colonoscopy
Examine the impact of candidate gene variants in the insulin-GH-IGF-IRS axis on colon polyps.
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.
Measured: at the time of the colonoscopy
Evaluate the association of dietary patterns, glycemic index (GI) and glycemic load (GL) with colon polyps.
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.
Measured: at 12 months
Synthesize the information on candidate genes and diet by looking at their joint effects on colon polyps
- 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.
Measured: at the time of the colonoscopy
To investigate the association of activated (phosphorylated) IRS1, AKT and mTOR with colon adenomas.
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.
Measured: at the time of the colonoscopy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2012 (estimated)
- Study start1 Apr 2012
- Primary completion11 Aug 2015
- Study completion11 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 3,315 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joseph E Willis, MD, Principal investigator, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01647776
- Sponsor's protocol ID
- CASE1207
- Other IDs
- SPORE 2
- Status last verified
- Feb 2021
- First submitted
- 5 Jul 2012
- Last updated
- 9 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Screening and Risk Factors of Colon Neoplasia
- ClinicalTrials.gov ID
- NCT01647776
- Acronym / sponsor ID
- CASE1207
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 3,315 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 1 Apr 2012
- Primary completion
- 11 Aug 2015 (actual)
- Study completion
- 11 Aug 2016 (actual)
- First posted
- 24 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Individuals without colon polyps | – | Other: Stool DNA Test, Procedure: biopsies of rectal and colon mucosa, Other: Questionnaires |
| Individuals with colon polyps | – | Other: Stool DNA Test, Procedure: biopsies of rectal and colon mucosa, Other: Questionnaires |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Average-risk patients undergoing colonoscopy at screening endoscopy centers in the University Hospitals of Cleveland system.
Key inclusion criteria (1 listed)
- patients undergoing routine colonoscopy at University Hospitals, Cleveland Ohio
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stool DNA TestAlso: sDNAStool DNA test is done prior to the colonoscopy. | Other | Individuals with colon polyps, Individuals without colon polyps |
| biopsies of rectal and colon mucosaDuring 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. | Procedure or surgery | Individuals with colon polyps, Individuals without colon polyps |
| QuestionnairesAlso: Food Frequency Questionnaire (FFQ), Meat Preparation Questionnaire (MPQ), Physical Activity Questionnaire (PAQ), Risk Factor Questionnaire (RFQ)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 | Individuals with colon polyps, Individuals without colon polyps |
Primary outcome
Stool DNA (sDNA) Feasibility and Compliance
Time frame: within 12 weeks prior to the colonoscopy
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
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
9 secondary outcomes
Concordance/discordance between tissue and stool DNA aberrant methylation markers
Time frame: Stool sample within 2 weeks of colonoscopy
Persistence of positive sDNA testing after removal of advanced adenomas
Time frame: at 12 months after initial colonoscopy
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
Insulin Resistance Syndrome
Time frame: at the time of the colonoscopy
Analyses stratified by ethnicity (Caucasians versus African Americans), and gender.
Time frame: at the time of the colonoscopy
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
Evaluate the association of dietary patterns, glycemic index (GI) and glycemic load (GL) with colon polyps.
Time frame: at 12 months
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
To investigate the association of activated (phosphorylated) IRS1, AKT and mTOR with colon adenomas.
Time frame: at the time of the colonoscopy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph E Willis, MD principal investigator
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colon Cancer, run by Case Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stool DNA (sDNA) Feasibility and Compliance (time frame: within 12 weeks prior to the colonoscopy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2021.