The Food Environment, Microbial Cysteine Metabolism, and Cancer Disparities

ConditionColorectal Cancer

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age45-75

SponsorPurdue University

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

Antibiotic use within the last 6 months

Abnormal gastrointestinal transit

A history of organ transplantation

Use of illicit drugs, combustible tobacco, or dietary supplements

Trial design

Design model

Crossover

Treatments tested in this trial

Low Cysteine Diet
Other intervention
A diet low in cysteine, about 1.4 g/1000 kcal.
High Cysteine Diet
Other intervention
A diet high in cysteine, about 3 g/1000 kcal.

Treatment groups

40 Participants

are divided into 2 treatment groups

Group A: High cysteine dietExperimental treatment 1 intervention

Group B: Low cysteine dietExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

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.

Time frame

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.

Time frame

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 outcomes

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.

Time frame

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.

Time frame

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

Time frame

Baseline, Week 1 (Day 8), Week 4 (Day 29), Week 8 (Day 57), Week 11 (Day 78)

Other outcomes

Psychosocial health

survey

Time frame

Baseline, Week 4 (Day 30), Week 8 (Day 58),Week 11 (Day 79)

Medication use

survey

Time frame

Baseline, Week 4 (Day 30), Week 8 (Day 58),Week 11 (Day 79)

Bowel habits

survey

Time frame

Baseline, Week 4 (Day 30), Week 8 (Day 58),Week 11 (Day 79)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Purdue University

Lead sponsor

American Cancer Society, Inc.

Collaborator

Indiana University

Collaborator

Source ClinicalTrials.gov

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