Stool DNA to Improve Colorectal Cancer Screening Among Alaska Native People

Randomized Controlled Trial of the Stool DNA Test to Improve Colorectal Cancer Screening Among Alaska Native People

Only 59% of Alaska Native people have been adequately screened for colorectal cancer (CRC) despite having the highest reported incidence of CRC in the world. A new at-home multi-target stool DNA screening test (MT-sDNA; Cologuard®) with high sensitivity for pre-cancerous polyps and CRC is now available. MT-sDNA has not been tested for feasibility or acceptability within the Alaska tribal health care delivery system, and it is unknown whether use of this new test will increase Alaska Native CRC screening rates. The long-term study goal is to improve screening and reduce CRC-attributable mortality. The objective of this application is to test the effectiveness of MT-sDNA for increasing CRC screening in Alaska Native communities using a mixed methods, community-based participatory research (CBPR) approach. The study will be conducted in collaboration with regional Tribal health organizations responsible for providing health care to geographically remote Alaska Native communities. Although the proposed implementation strategy is evidence-informed and promising, it is novel in that MT-sDNA has not been evaluated in the tribal health setting or among rural/remote populations. Using the Social Ecological Model, the research will be multi-level, examining influence on patients, providers, and tribal health organizations (THOs). This research study will pursue two specific aims: (1) Identify patient-, provider-, and system-level factors associated with CRC screening preferences, uptake, and follow-up; and (2) test the effectiveness of graded intensity MT-sDNA intervention in the Alaska Native community setting. For the first aim, focus groups with Alaska Native people who are not adherent to CRC screening guidelines and interviews with healthcare providers will be used to identify factors for future intervention. For the second aim, a three-arm cluster randomized controlled trial (high intensity with patient navigation, medium intensity with mailed reminders, usual care) will provide evidence on the MT-sDNA usefulness (MT-sDNA sample quality and neoplastic yield) as well as the first data on MT-sDNA follow up adherence rates in the Alaska Native population, which will inform plans to scale-up the intervention model. This research has the potential to sustainably improve public health by increasing CRC screening rates among a rural/remote tribal population as well as provide a model for other integrated health systems that provide care to high-risk or underserved populations in the U.S. and worldwide.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Diagnostic test: multi-target stool DNA test

Detailed Description

The study will employ a cluster-randomized design, in which 26 communities within one Tribal health region will be randomized to one of the two study intervention conditions, matched by community size. All Alaska Native adults aged 45-75 due for colorectal cancer (CRC) screening within each community will be offered the same intervention. At least 770 participants will be recruited in at least 13 communities per study arm.

1. High Intensity Intervention: Participants will receive navigated tribal health worker outreach, a mailed MT-sDNA kit, mailed culturally appropriate educational material describing CRC screening options available and follow-up reminders
2. Medium Intensity Intervention: Participants will receive mailed culturally appropriate educational material describing CRC screening options available, including MT-sDNA, and navigated follow-up outreach reminders
3. Usual Care (Control arm): All other communities in the participating Tribal health region will serve as the reference group receiving usual care (i.e., screening recommendation at a clinic visit) Participants receiving the high intensity intervention are expected to have a 20% increase in screening uptake while those receiving medium intensity intervention will have a 10% increase in screening uptake over those receiving usual care. The study will also measure MT-sDNA sample quality and neoplastic yield in these remote Alaska Native communities. The investigators anticipate that the proportion of MT-sDNA tests meeting quality control standards will be the same as in the general US population (96%) and that pre-cancerous polyp detection rates at diagnostic post-MT-sDNA colonoscopy will exceed routine clinical practice rates in the general US population (52%-67%).

During and following the graded intensity intervention, the investigators will survey samples of patients to evaluate their awareness and response to the CRC screening intervention. The investigators will assess their perceived severity, perceived susceptibility, perceived benefits, perceived barriers, and self-efficacy relevant to CRC screening as well as measure the time-to-respond and screening method used. The study will use focus groups and key informant interviews to learn about factors associated with screening response. For the focus groups, AN people ages 45-75 who are unscreened or non-adherent to screening guidelines (colonoscopy within 10 years, sigmoidoscopy within five years, or fecal occult blood testing within preceding 12 months) will be invited to provide their views on barriers to and facilitators of screening, including barriers described in the literature and identified in the investigators previous work. Non-adherence will be identified through tribal medical records. Each focus group will last up to two hours, and will include 6-8 participants. All focus groups will be stratified by gender, and focus groups will be balanced so that approximately equal numbers of men and women are included in the analysis.

The investigators will also conduct a brief survey and key informant interviews (6-8 clinician interviews at each location) among community health aides, providers, and tribal health system administrators using validated measures of intervention feasibility, acceptability, and appropriateness to characterize provider- and system-level barriers and promotors to MT-sDNA implementation.

• Study Type: Interventional
• Enrollment (Anticipated): 1540
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Bethel, Alaska, United States, 99559
      • Recruiting
      • Yukon-Kuskokwim Health Corporation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Alaska Native adults eligible to receive health care through the Alaska Tribal Health System
• Active health system users with at least one Alaska Tribal Health System visit in the previous three years
• Due for colorectal cancer screening (have not had colonoscopy in past 10 years or fecal occult blood test in past 1 year or flexible sigmoidoscopy in past 5 years)

Exclusion Criteria:

• History of familial adenomatous polyposis
• Hereditary non-polyposis CRC
• Previous colonoscopic evidence of inflammatory bowel disease, Crohn's disease, colorectal adenomas, or CRC
• Known history of colectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SCREENING
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: High Intensity; navigated tribal health worker outreach, a mailed MT-sDNA kit, mailed culturally appropriate educational material describing CRC screening options available and follow-up reminders	Diagnostic test: multi-target stool DNA test; Cluster randomized trial of high and medium intensity outreach with MT-sDNA compared with usual care; Other Names: Cologuard
ACTIVE_COMPARATOR: Medium Intensity; navigated tribal health worker outreach, a mailed MT-sDNA kit, mailed culturally appropriate educational material describing CRC screening options available and follow-up reminders	Diagnostic test: multi-target stool DNA test; Cluster randomized trial of high and medium intensity outreach with MT-sDNA compared with usual care; Other Names: Cologuard
NO_INTERVENTION: Usual Care; usual care (i.e., opportunistic screening recommendation at a clinic visit)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colorectal cancer screening	Incident CRC screening episode defined as having at least one of the following within 1 year of follow-up after randomization and intervention: colonoscopy; MT-sDNA with a negative result; or MT-sDNA with a positive result followed by a colonoscopy within 90 days.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic follow-up	Rate of positive MT-sDNA test follow up to diagnostic colonoscopy	1 year

Collaborators and Investigators

• Sponsor: Alaska Native Tribal Health Consortium
• Collaborators: Mayo Clinic

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 29, 2021
• Primary Completion (ANTICIPATED): March 31, 2025
• Study Completion (ANTICIPATED): March 31, 2025

Study Registration Dates

• First Submitted: April 3, 2020
• First Submitted That Met QC Criteria: April 3, 2020
• First Posted (ACTUAL): April 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 4, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: screening
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 1R01CA247642-01 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pending Tribal approval, the final combined dataset can be shared as a completely de-identified dataset as defined by the Health Information Portability and Accountability Act and excluding any variable causing risk of identification due to small numbers.
• IPD Sharing Time Frame: 2025
• IPD Sharing Access Criteria: Interested investigators would be required to enter into a data sharing agreement with the Alaska Native Tribal Health Consortium that includes the following: 1) a commitment to follow the Tribal approval process from concept proposal to dissemination; 2) a commitment to using the data only for research purposes and not to identify any individual participant; 3) a commitment to securing the data using appropriate computer technology; and 4) a commitment to destroying or returning the data after analyses are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No