The Food Environment, Microbial Cysteine Metabolism, and Cancer Disparities

The goal of this clinical trial is to learn if changing cysteine levels in the diet can influence how the body processes cysteine in Black and White individuals aged 45-75 with a history of non-cancerous polyps. The main questions it aims to answer are:

• At the beginning of the study, do Black participants have higher levels of cortisol (a stress hormone) and compounds made from cysteine in their blood when compared to White participants?
• Does eating less cysteine lower the body's natural cysteine activity and lead to less gut bacteria that break down cysteine?
• Does eating less cysteine lead to less inflammation in the gut and lower levels of markers of inflammation in the blood?

Research will compare a high cysteine diet and a low cysteine diet, and each participant will eat both diets.

Participants will be in the study for 11 weeks and 2 days. Over the course of the study, participants will:

• Eat a high cysteine diet for 3 weeks, and a low cysteine diet for 3 weeks
• Eat a moderate cysteine diet for 1 week before each study diet
• Complete surveys
• Provide blood, stool, and saliva samples
• Maintain food logs

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Other: High Cysteine Diet; Other: Low Cysteine Diet

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Patricia G Wolf, PhD, RD; Phone Number: 765-494-1860; Email: wolfpm@purdue.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Not yet recruiting
      • University Hospital Clinical Research Center
      • Contact: Ariana Moffitt, MPH; Phone Number: 765-494-1860; Email: amoffit@purdue.edu
    • West Lafayette, Indiana, United States, 47906
      • Recruiting
      • Purdue Clinical Research Center
      • Contact: Ariana Moffitt, MPH; Phone Number: 765-494-1860; Email: amoffit@purdue.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 45-75
• Up to date with CRC screening colonoscopy with a high risk of CRC, defined as a history of 3 or more adenomatous polyps (APs) or an AP >1 cm in the past 5 years
• Identify as Black or Non-Hispanic White
• If female, no menstrual period for at least six months
• Willingness to donate oral wash and stool samples
• Willingness to complete 24-hour dietary recalls

Exclusion Criteria:

• Antibiotic use within the last 6 months
• Abnormal gastrointestinal transit
• A history of organ transplantation
• Use of illicit drugs, combustible tobacco, or dietary supplements
• Pre- or probiotics within the last two months
• A history of cancer treatment within the past 12 months
• CRC or a genetic predisposition to CRC
• A baseline body weight > 450 lbs
• Weight gain or loss > 4 kg 3 months prior to study
• Significant food allergies, food preferences or therapeutic or vegetarian diets
• Menstrual cycle within the last 6 months
• Antibiotics in the last 2 months
• Cannot keep a food record for 7 consecutive days during screening after detailed instruction
• Significant medical conditions
• History of eating disorders
• Alcoholism
• Individuals under the age of 18

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High cysteine diet; Participants will eat a diet higher in cysteine, relying on more animal based protein.	Other: High Cysteine Diet; A diet high in cysteine, about 3 g/1000 kcal.
Experimental: Low cysteine diet; Participants will eat a diet lower in cysteine, relying on more plant based protein.	Other: Low Cysteine Diet; A diet low in cysteine, about 1.4 g/1000 kcal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colonic inflammation	Fecal calprotectin, a marker of intestinal inflammation, will be measured from 100 mg of stool collected at the respective timeframe using a CALPRO Calprotectin ELISA test.	Baseline, Week 1 (Day 8), Week 2 (Day 15), Week 4 (Day 29), Week 7 (Day 49), Week 8 (Day 57), Week 9 (Day 64), Week 11 (Day 78)
Fecal microbial content	Microbial genomic DNA will be extracted from stool obtained at the respective timeframe using a Qiagen DNeasy PowerSoil Kit. Genomic DNA will be fragmented using a Covaris S2 and processed into libraries using an Integrated DNA Technologies xGen DNA Library Prep Kit. Final libraries will be pooled and sequenced on an Illumina NovaSeq X using 25B chemistry.	Baseline, Week 1 (Day 8), Week 2 (Day 15), Week 4 (Day 29), Week 7 (Day 49), Week 8 (Day 57), Week 9 (Day 64), Week 11 (Day 78)
Systemic markers of inflammation	Serum from blood collected at the respective timeframe will be analyzed in triplicate with the Bio-Plex® Precision Pro™ (Bio rad, Hercules, CA) human cytokine 10-plex immunoassay to detect IL-1β, IL-6, IFN-γ, TNF-α, IL-2, IL-4, IL-5, IL-10, IL-12 (p70) and IL-13.	Baseline, Week 1 (Day 9), Week 2 (Day 16), Week 3 (Day 23), Week 4 (Day 30), Week 7 (Day 50), Week 8 (Day 58), Week 9 (Day 65), Week 11 (Day 79)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of serum hydroxycortisol and cysteine metabolism markers	Serum hydroxycortisol and measures of cysteine metabolism (cysteine, homocysteine, lanthionine, cystathionine, serine) will be determined using hydrophilic interaction liquid chromatography with triple quadrupole tandem mass spectrometry by the Purdue Metabolite Profiling Facility.	Baseline, Week 1 (Day 9), Week 2 (Day 16), Week 3 (Day 23), Week 4 (Day 30), Week 7 (Day 50), Week 8 (Day 58), Week 9 (Day 65), Week 11 (Day 79)
Absolute and relative quantification of microbial cysteine metabolic genes	Microbial genomic DNA will be extracted from stool obtained at the respective timeframe using a Qiagen DNeasy PowerSoil Kit. To estimate gene content, metagenomic libraries will be constructed from stool DNA. Metagenomic data will be processed to filter potential host DNA sequences and remove low-quality reads. Raw shotgun data will be assembled using MEGAHIT and assembled contigs will be binned using MetaBAT2. Taxonomic classification of binned contigs will be performed using CAT/BAT and differences genera that have functional genes for sulfur metabolism will be assessed. Assembled and binned metagenomes will be surveyed for genes for cysteine metabolism using custom hidden Markov model (HMM) libraries.	Baseline, Week 1 (Day 8), Week 2 (Day 15), Week 4 (Day 29), Week 7 (Day 49), Week 8 (Day 57), Week 9 (Day 64), Week 11 (Day 78)
Exfoliated intestinal epithelial cell transcriptomics	Exfoliated intestinal epithelial cells separated from stool collected at the respective timeframe with gene expression analysis	Baseline, Week 1 (Day 8), Week 4 (Day 29), Week 8 (Day 57), Week 11 (Day 78)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychosocial health	survey	Baseline, Week 4 (Day 30), Week 8 (Day 58),Week 11 (Day 79)
Medication use	survey	Baseline, Week 4 (Day 30), Week 8 (Day 58),Week 11 (Day 79)
Bowel habits	survey	Baseline, Week 4 (Day 30), Week 8 (Day 58),Week 11 (Day 79)

Collaborators and Investigators

• Sponsor: Purdue University
• Collaborators: American Cancer Society, Inc.; Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 17, 2025
• First Submitted That Met QC Criteria: July 17, 2025
• First Posted (Actual): July 25, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Neoplasms; Intestinal Diseases; Colorectal Cancer; Colorectal Neoplasms; Colonic Diseases; Dietary Intervention; Gut Microbiome; Cancer Prevention; Intestinal Neoplasms; Colorectal Cancer Prevention; Colorectal Adenomas; Cysteine Metabolism; Diet modification; Colorectal Cancer Risk
• Additional Relevant MeSH Terms: Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Rectal Diseases; Neoplasms; Colonic Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Intestinal Diseases
• Other Study ID Numbers: IRB-2023-1426; RSG-23-1154989-01-CSCT (Other Grant/Funding Number: American Cancer Society)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No