Long-term Follow-up Study Designed to Evaluate the Relative Risk of Two Colonoscopy Schedules for Patients With Small Polyps

This study has been completed.
Sponsor:
Collaborator:
Central Lab
Information provided by:
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00032344
First received: March 18, 2002
Last updated: November 19, 2010
Last verified: November 2010
  Purpose

Colorectal cancer is a leading cause of cancer death in the United States. Mortality remains high because most colorectal cancers are detected after there has been regional or distant spread, precluding curative surgical resection. With this in mind, screening strategies have been recommended for asymptomatic individuals which hope to reduce mortality from colon cancer by detecting and removing premalignant adenomatous polyps or early malignant lesions. Screening of asymptomatic individuals over age 50 with sigmoidoscopy and fecal occult blood tests has been advocated by the American Cancer Society. However, current screening will identify only 50% of patients who have adenomatous polyps. More sensitive tests for polyp detection, like colonoscopy, are costly, require extensive resources and are unlikely to be used for screening large populations. Ideal screening would identify patients with the highest risk of cancer and target more sensitive screening tests at this population. The identification of low cost, easily collectible risk factors which can be used to target patients for the more sensitive screening tests is the primary purpose of this study. Since a major segment of the veteran population is over the age of 50, there will be a substantial impact in reduction of both mortality and morbidity due to colon cancer and attendant cost savings to the VA for treatment if such risk factors can be identified.

Phase I is a cross-sectional study designed to identify risk factors for large (>1 cm) adenomatous polyps. Approximately 3200 asymptomatic subjects (age 50-75) have completed risk factor assessment, medical and dietary histories, and have undergone complete colonoscopy examination. This will identify for comparison purposes a polyp-free control group and is the first large prospective study to include such a group. Data at colonoscopy will characterize the prevalence, size and distribution of adenomatous polyps. This will permit an assessment of sensitivity of sigmoidoscopy in this population. In addition, tissue from normal rectal mucosa will be analyzed for evidence of cell proliferation activity. The primary focus of Phase I is a risk factor analysis. A multivariate analysis will be performed to determine the relationship of historical and environmental factors as well as cell proliferation activity with the presence of adenomatous polyps. A cohort consisting of a subgroup of polyp patients (large and small) and matched polyp-free controls will be tracked longitudinally to determine polyp occurrence/recurrence rates.

Phase II of the study is a long-term follow-up study designed to evaluate the relative risk of two repeat colonoscopies.

Phase III is an extension in follow-up of an additional five years, a total of ten years in all, to include all study patients. The primary focus will be on documenting long-term mortality and medical outcomes as well as occurrence/reoccurrence of neoplasia with special emphasis on ten-year cancer rates.


Condition Intervention Phase
Colorectal Cancer
Procedure: Colonoscopy
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: CSP #380 - Prospective Evaluation of Risk Factors for Large (> 1 CM) Colonic Adenomas in Asymptomatic Subjects

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Phase I: Risk factors include: family history; dietary; fat, fiber, calcium; alcohol history; tobacco use; physical activity; obesity; NSAID use; and, biomarkers: BRDU, PCNA [ Time Frame: Cross-sectional ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase II: Colonoscopy outcomes to determine recurrence rates and compare surveillance strategies [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Phase III: Medical outcomes including mortality. Colonoscopy outcomes in subgroup of polyp free patient at baseline to determine long term risk. [ Time Frame: 10 years ] [ Designated as safety issue: No ]

Enrollment: 3200
Study Start Date: October 1993
Study Completion Date: February 2007
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1
Phase I - Cross-sectional; Phase II - 5 year follow-up; Phase III - 10 year follow-up
Procedure: Colonoscopy
Phase I - Cross-sectional; Phase II - 5 year follow-up; Phase III - 10 year follow-up

  Hide Detailed Description

Detailed Description:

Primary Hypothesis: Risk factors can be determined for large (>1 cm) adenomas, precursor lesions for colorectal cancer.

Secondary Hypothesis: Determine long-term rates for development or recurrence of polyps; determine sensitivity/specificity of current colon cancer screening strategies; determine relationship of dietary factors and biomarkers of cell proliferation; determine the efficacy and safety of long-term (5 years) repeat colonoscopy in patients with small polyps.

Intervention: Phase I: All patients undergo full colonoscopy. Phase II: Randomization to repeat colonoscopy at 2-3 years and 5 years after baseline, or, repeat colonoscopy at 5 years only. Phase III: Ten-year follow-up on all Phase I patients for medical outcomes. Repeat colonoscopy at 10 years on polyp-free patients (Phase I) aged 50-64.

Primary Outcomes: Presence of risk factors and adenomatous polyps including prevalence, descriptive characteristics, and long-term occurrence/recurrence rates.

Study Abstract: Phase I is a cross-sectional study designed to identify risk factors for large (>1 cm) adenomatous polyps. Approximately 3200 asymptomatic subjects (age 50-75) have completed risk factor assessment, medical and dietary histories, and have undergone complete colonoscopy examination. This will identify for comparison purposes a polyp-free control group and is the first large prospective study to include such a group. Data at colonoscopy will characterize the prevalence, size and distribution of adenomatous polyps. This will permit an assessment of sensitivity of sigmoidoscopy in this population. In addition, tissue from normal rectal mucosa will be analyzed for evidence of cell proliferation activity. The primary focus of Phase I is a risk factor analysis. A multivariate analysis will be performed to determine the relationship of historical and environmental factors as well as cell proliferation activity with the presence of adenomatous polyps. A cohort consisting of a subgroup of polyp patients (large and small) and matched polyp-free controls will be tracked longitudinally to determine polyp occurrence/recurrence rates.

Phase II of the study is a long-term follow-up study designed to evaluate the relative risk of two repeat colonoscopy schedules for patients with small polyps identified in Phase I of the study. Recruitment is complete with 615 patients eligible (of the target 808) assigned at random to either repeat colonoscopy at 2-3 years and 5 years, or to repeat colonoscopy at 5 years only. This phase will also provide preliminary longitudinal risk factor information related to occurrence/recurrence of polyps.

Phase III was a 5-year extension of follow-up period. All Phase I patients were to be reconsented to provide medical outcome data for a period of 10 years from baseline exam. Phase I patients polyp-free, aged 50-64 will be offered repeat colonoscopy at 10 years to evaluate long-term risk.

Results (Phase I): 3121 patients had complete colonoscopy which revealed high rates of neoplasia: 37.5% had one or more neoplastic lesions; 10.5% had advanced neoplasia including 30 cases of invasive cancer (1%). There were 3.7% of patients with no lesions in the rectum or sigmoid colon who had advanced neoplasia elsewhere in the colon: 32% of all patients with advanced neoplasia would not be detected with an exam of the rectum or sigmoid colon (distal); 62% of patients with proximal advanced neoplasia would not be detected with an exam of the rectum and sigmoid colon. There were few serious complications (0.3%).

The one-time fecal occult blood test (FOBT) was evaluated as a diagnostic test for advanced neoplasia. A positive FOBT indicated an increased likelihood (3-4x) of advanced neoplasia. However, one-time FOBT failed to detect 75% of patients with advanced neoplasia.

The primary analysis of risk factors (Phase I) found positive associations (for advanced neoplasia) for history of a first degree relative with colorectal cancer (OR, 1.66; 95% CI, 1.16-2.35), current smoking (OR, 1.85; 95% CI, 1.33-2.58), and current moderate to heavy alcohol use (OR, 1.02, 95% CI, 1.01-1.03). Inverse associations were found for cereal fiber intake (OR, 0.95, 95% CI, 0.91-0.99), vitamin D intake (OR, 0.94, 95% CI, 0.90-0.99), and use of NSAIDs (OR, 0.66, 95% CI, 0.48-0.91). Results appeared in JAMA (2003;290:2959-2967).

Phase III is completed with patients completing their scheduled follow-ups. A major manuscript on the sensitivity/specificity of digital rectal exam appeared in Annals of Internal Medicine January, 2005. The Phase II results manuscript appeared in Gastroenterology in October 2007.

  Eligibility

Ages Eligible for Study:   50 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Study Complete

Exclusion Criteria:

  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: NCT00032344

Locations
United States, Arizona
Carl T. Hayden VA Medical Center
Phoenix, Arizona, United States, 85012
Southern Arizona VA Health Care System, Tucson
Tucson, Arizona, United States, 85723
United States, California
VA Medical Center, Long Beach
Long Beach, California, United States, 90822
VA Palo Alto Health Care System
Palo Alto, California, United States, 94304-1290
VA Medical Center, San Francisco
San Francisco, California, United States, 94121
United States, Colorado
VA Eastern Colorado Health Care System, Denver
Denver, Colorado, United States, 80220
United States, Illinois
Edward Hines, Jr. VA Hospital
Hines, Illinois, United States, 60141-5000
United States, Minnesota
VA Medical Center, Minneapolis
Minneapolis, Minnesota, United States, 55417
United States, Missouri
VA Medical Center, Kansas City MO
Kansas City, Missouri, United States, 64128
United States, North Carolina
VA Medical Center, Durham
Durham, North Carolina, United States, 27705
United States, Oregon
VA Medical Center, Portland
Portland, Oregon, United States, 97239-2964
United States, Texas
VA North Texas Health Care System, Dallas
Dallas, Texas, United States, 75216
United States, Vermont
VA Medical & Regional Office Center, White River
White River Junction, Vermont, United States, 05009-0001
Sponsors and Collaborators
Central Lab
Investigators
Study Chair: David Lieberman, MD VA Medical Center, Portland
  More Information

Publications:
Responsible Party: Lieberman, David - Study Chair, Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00032344     History of Changes
Other Study ID Numbers: 380
Study First Received: March 18, 2002
Last Updated: November 19, 2010
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
large (>1 cm) adenomas

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

ClinicalTrials.gov processed this record on September 16, 2014