Non-Invasive Prediction of Colorectal Neoplasia (NIPCON)

Hypothesis:The Adnab-9 antigen is a predictive biomarker in individuals at risk of developing colorectal neoplasia.

Study aim is to evaluate the potential of the Adnab-9 monoclonal antibody (MAb) as a marker of cancer risk in a population at increased risk for colorectal cancer (CRC). This marker would be compared to other current and emerging diagnostic methods. 2,800 Veterans would be recruited into the study. In phase 1, candidates would be defined as having increased CRC risk by a short questionnaire. Stool samples would be obtained and a semi-quantitative Adnab-9 antigen assay (ELISA) would be determined. Patients with differing high and low estimations of fecal Adnab-9 would undergo colonoscopy at which time other samples of effluent and colonic mucosa would be taken, and a detailed lifestyle and nutritional questionnaire would be completed. The characteristics of the Adnab-9 fecal test as a diagnostic test would be critically determined using the outcome of the colonoscopic and other test results. The patients will be contacted through the mail and by word of mouth. Informed consent will be obtained before the samples are obtained. The participants are clinically defined as high-risk and therefore screening colonoscopy would be likely performed in any event. A number of assays for Adnab-9 are feasible including slot-blot, Western blot, and ELISA. Other stool studies include conventional fecal occult blood tests (FOBT or FIT) that will be performed in tandem. The investigators therefore began this method of collection and obtained consent from over 2000 patients with a similar overall compliance rate with FOBT screening procedures to that reported previously of approximately 50%. Currently the study is no longer enrolling patients at the Detroit VA and is now finalizing data entry. Another 450 patients to be recruited at the Philadelphia VAMC.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer; Colonic Polyps; Polyposis Coli

Detailed Description

The primary objectives is to test the efficacy of Adnab-9 stool testing in a population at high-risk for colorectal neoplasia and directly compare it to that of the FOBT and secondarily, identify the source of the Adnab-9 antigen to determine influences of diet and environment on its expression. The design is a prospective cross sectional (Part 1) and a case-control longitudinal follow-up study (Part 2) using a brief questionnaire to assess risk for cancer in a total of 2800 Part I patients will be enrolled designed to achieve a database of high risk individuals and measure fecal Adnab-9 levels before a clinically indicated colonoscopy is performed. The patients submit 4 FOBT cards in a routine manner by mail, 3 are used for the FOBT and stool is extracted from the last card for the Adnab-9 ELISA which is reported as OD/5ug protein/well. 100 Part 2 enrollees are then selected on the basis of positive fecal Adnab-9 test candidates matched with a like number of patients with negative stool results who have had their initial colonoscopy and who will have a 5-year follow-up colonoscopy. Detailed Adnab-9 testing (immunohistochemical Adnab-9 binding; blood biomarker estimations and Adnab-9 Western blotting) will be performed on various bodily fluids to perfect the method of testing and completion of the detailed questionnaire to check for reproducibility and interim lifestyle changes in these participants.

• Study Type: Observational
• Enrollment (Actual): 2282

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia Vamc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Greater than average risk for colorectal neoplasia

Description

Inclusion Criteria:

• ability to complete a consent form
• must be at above average risk for colorectal neoplasia
• physically able to undergo colonoscopy or barium enema

Exclusion Criteria:

• Mentally handicapped
• Physically infirm
• Low risk for colorectal neoplasia
• Pregnant individuals
• Vulnerable populations

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
colorectal neoplasia; No interventions Record colorectal neoplasia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of Adnab-9 stool result with outcome of colonoscopy	Stool is collected on guaiac stool cards and/or stool Polymedco sample bottle and extracted. Extracted stool is assayed for protein content and this is used as a standard for the Adnab-9 ELISA. Record review note colonoscopy outcome which is correlated with Adnab-9 ELISA result.	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Define the origin of the Adnab-9 bound antigen	Biopsies are taken at the time of colonoscopy in ~10% of initial enrollees, from 6 colonic segments. In addition colonic effluent. saliva, urine and blood samples are taken. ELISA and immunohistochemistry for Adnab-9 binding are performed.	10 years

Collaborators and Investigators

• Sponsor: Corporal Michael J. Crescenz VA Medical Center
• Investigators: Principal Investigator: Martin Tobi, MB,ChB, Philadelphia VAMC (WOC) Detroit VAMC (WOC) Saginaw VAMC; Principal Investigator: Fadi Antaki, MD, Detroit VAMC; Principal Investigator: John Lieb, MD, Philadelphia PVAMC

Publications and helpful links

General Publications

• Tobi M, Prabhu S, Gage RE, Orr T, Lawson MJ. Colorectal cancer risk: the impact of evidence of a field effect of carcinogenesis on blinded diagnosis using an anti-adenoma antibody test performed on colonoscopic effluent. Dig Dis Sci. 2002 Feb;47(2):317-21. doi: 10.1023/a:1013713920805.
• Tobi M, Elitsur Y, Moyer MP, Halline A, Deutsch M, Nochomovitz L, Luk GD. Mucosal origin and shedding of an early colonic tumor marker defined by Adnab-9 monoclonal antibody. Scand J Gastroenterol. 1993 Dec;28(12):1025-34. doi: 10.3109/00365529309098304.
• Tobi M, Maliakkal B, Zitron I, Alousi M, Goo R, Nochomovitz L, Luk G. Adenoma-derived antibody, Adnab-9 recognizes a membrane-bound glycoprotein in colonic tissue and effluent material from patients with colorectal neoplasia. Cancer Lett. 1992 Oct 30;67(1):61-9. doi: 10.1016/0304-3835(92)90009-k.

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: March 18, 2013
• First Submitted That Met QC Criteria: March 18, 2013
• First Posted (Estimate): March 21, 2013

Study Record Updates

• Last Update Posted (Estimate): September 27, 2016
• Last Update Submitted That Met QC Criteria: September 26, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: monoclonal antibody; colonoscopy; FIT; stool; Adnab-9; FOBT; iFOBT; barium enema; flexible sigmoidoscopy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Colonic Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Intestinal Neoplasms; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; Polyps; Intestinal Polyps; Adenomatous Polyps; Adenoma; Intestinal Polyposis; Colonic Polyps; Adenomatous Polyposis Coli
• Other Study ID Numbers: 00919; 0409000159 (Other Grant/Funding Number: 096294M1F)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No