Reducing Metabolic Dysregulation in Dyads (REMEDY)

A Transdisciplinary Approach to Investigating Metabolic and Risk of Early-Onset Colorectal Cancer: A Randomized Intervention Trial in Human Dyads and Mechanistic Study in Animals

This study is a 6-month randomized controlled trail of diet modification designed to reduce chronic inflammation and reverse metabolic dysfunction among obese individuals with one or more polyps found at a colonoscopy screening. We also will recruit an at least overweight partner, who lives in the same household. To be eligible, participants will be apparently disease-free, obese AAs or EAs who have self-identified a partner who is at least 9 years, with whom they live and who also is at least overweight. Each index participant will: 1) Be AA or EA by self-report; 2) Be ≤55 years old; 3) Have undergone a colonoscopy screening and found to have ≥1 polyp(s); 4) Be free of co-morbid conditions or other factors that would limit participation in this trial; 5) Have a BMI ≥30kg/m2; 6) Be willing to commit to investing the time and effort required to participate in this trial (i.e., willing to complete all assessments and provide biological samples as specified in the consent); and 7) Have no recent antibiotic use. Their partner needs to: 1) Be at least 9 years old; 2) Live in the same household and consumes meals together; 3) Be at least overweight; 4) Agree to all study procedures, including provision of biological samples, body measurements, and self-reported dietary and other assessments; and 5) Have no recent antibiotic use.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Colorectal Cancer; Nutrition Related Cancer
• Intervention / Treatment: Behavioral: IMAGINE HEALTHY

Detailed Description

This project leverages our expertise in the epidemiology of colorectal cancer (CRC); disparities; obesity; metabolic dysregulation, an important manifestation of inflammation; the microbiome; animal CRC models; and lifestyle intervention trials to address the growing problem of Early-Onset CRC (EOCRC) (i.e., <50 years). Adiposity and diet drive metabolic dysregulation. So, understanding the interaction between diet and adiposity are key to understanding the genesis of EOCRC - and an array of other obesity-related cancers. This project will address the absence of critical clinical trials and mechanistic studies involving lifestyle interventions for EOCRC. We intend to address this gap; and have the transdisciplinary team representing complementary backgrounds to do so. We focus on dietary modulation of gut microbes to reduce metaflammation and subsequent metabolic dysfunction in obesity, with a goal of preventing EOCRC. We will perform an anti-inflammatory dietary intervention trial in dyads of adults and children at elevated risk for CRC. We also will conduct a complementary mechanistic animal study that builds on and leverages our expertise in mechanistic studies on obesity and CRC. This work is supported by infrastructure that we have built over the past decades in two key centers at the University of South Carolina (USC): (1) Center for Colon Cancer Research (CCCR, 2002 - present - which specializes in mouse models of CRC); and (2) the Cancer Prevention and Control Program (CPCP, 2003 - present - which specializes in the epidemiology of cancer and lifestyle intervention trials for cancer, with a focus on cancer disparities). The two projects that comprise the proposed grant address two Specific Aims that are represented by the human study and laboratory animal experiment: i.e. ,1: To establish the metabolic protective effects of an anti-inflammatory diet in obese, high-risk African-American (AA) and European-American (EA) adults and children in reducing inflammation as indicated by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), IGF-1, Tumor Necrosis Factor alpha (TNFα), Interleukin 6 (IL-6), and C-Reactive Protein (CRP), and a creating more favorable microbiome signature; 2: To establish gut microbes as mediators between anti-inflammatory dietary input and reversal of metabolic dysfunction and associated CRC risk. This complements the human study by carrying out pre-clinical murine model studies with similar inputs (diet), intermediate endpoints (inflammation, microbiome), and outcomes (CRC-related). We hypothesize that an anti-inflammatory dietary intervention will reduce metabolic dysfunction and metainflammation through regulatory effects on gut microbiota.

Results from this work will address the role of metabolic dysregulation in relation to factors that are known to be important in carcinogenesis, that therefore could have profound effects on EOCRC, have implications for other obesity-related cancers, and have great promise for moving the field forward by addressing mechanisms that drive large health-related disparities that consistently disfavor African Americans.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Columbia, South Carolina, United States, 29208
      • Recruiting
      • University of South Carolina
      • Contact: James R Hebert, ScD; Phone Number: 803-576-5613; Email: jhebert@sc.edu
      • Contact: Gauri Sathe; Phone Number: 803-576-5613; Email: satheg@mailbox.sc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Individuals eligible to participate in this study will be apparently disease- free, obese (BMI ≥ 30kg/m2) AAs or EAs who have self-identified a partner who is at least 9 years old, with whom they live and who also is at least overweight. Each index patient will: 1) Be AA or EA by self-report; 2) Be ≤55 years old; 3) Have agreed to undergo colonoscopy screening and found to have ≥1 polyp(s) that place them at elevated risk for future adenomas and CRC; 4) Be free of co-morbid conditions or other factors that would limit participation in this trial; 5) Have a BMI ≥30kg/m2; 6) Be willing to commit to investing the time and effort required to participate in this trial (i.e., willing to complete all assessments and provide biological samples as specified in the consent); and 7) Have no recent antibiotic use (≤3 months). Their dyad partner needs to: 1) Be at least 9 years old; 2) Live in the same household and consumes meals together; 3) Be at least overweight; 4) Agree to all study procedures, including provision of biological samples, anthropometric measurements, and self-reported dietary and other assessments; 5) Have no recent antibiotic use (≤3 months).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Comparison; Participation will be for six months. Participants will meet staff at three timepoints (baseline, 3 months, 6 months) to complete questionnaires, online dietary assessment, body measures, have blood pressure measured, provide blood and stool samples, and wear an activity monitor for a week at each time point.
Experimental: Intervention; Participation will be for six months. Participants will meet staff at three timepoints (baseline, 3 months, 6 months) to complete questionnaires, online dietary assessment, body measures, have blood pressure measured, provide blood and stool samples, and wear an activity monitor for a week at each time point. In addition, participants will attend weekly classes for 12 weeks and one class per month for three months. These classes will include cooking, movement, and stress reduction.	Behavioral: IMAGINE HEALTHY; An anti-inflammatory nutrition program including cooking classes, physical activity, and stress reduction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood	Tumor Necrosis Factor alpha (TNFα), Interleukin 6 (IL-6), and C-Reactive Protein (CRP)	Baseline, 3-month, 6-month
Stool	Determine race-specific microbiome signatures associated with anti-inflammatory dietary input and reversal of metabolic dysfunction	Baseline, 3-month, 6-month

Collaborators and Investigators

• Sponsor: University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: October 30, 2023
• First Submitted That Met QC Criteria: October 30, 2023
• First Posted (Actual): November 3, 2023

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 27, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Microbiome; Body Composition; Digestive System
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Pathological Conditions, Signs and Symptoms; Neoplasms; Colorectal Neoplasms; Inflammation
• Other Study ID Numbers: Pro00120270

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The information collected for this study will also be transferred into a secure, electronic database at the Biostatistics Center of George Washington University. The database will have information from all the participants as well as from other related studies. Information will not include directly identifying information such as name, address, social security number, or medical record number. The study will use a unique code for each person consisting of a set of letters and numbers. The key to the code linking the data to the participant will be kept at USC in a secure manner. Information in the database will only be used for statistical analyses. At the conclusion of the study, some biological samples as well as data from USC may be shared with biospecimen and data repositories supported by the NIH, which funded this study. Data and biological samples sent to these repositories will be identified only by a code number and cannot be linked to a participant.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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