Microbiome-based Diagnostic Tool for the Screening of Colorectal Cancer (GUILTI)

NCT06738173 | Recruiting

• 2 other identifiers: 708530203
• Study Type: observational
• Target: 1,202
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer (CRC) is one of the most common cancer and cause of cancer death worldwide. Population-based screening programs for average risk populations have proven effective in reducing both incidence and mortality of CRC through early detection of cancer. The fecal immunochemical testing (FIT), has still a suboptimal diagnostic yield, with both missed adenomas and, mainly, unnecessary colonoscopies.The identification of novel, non-invasive biomarkers is currently one of the research areas driving most expenditure forces in the field of CRC.A large body of evidence shows that alterations of the gut microbiome and the enrichment of specific taxa(e.g. Fusobacterium nucleatum, Parvimonas micra, and others) are involved in the pathogenesis of CRC. Moreover, recent studies, have discovered common microbial signatures able to reproducibly discriminate between patients with CRC and healthy controls.The goal of this observational study to develop a gut microbiome based diagnostic tool for the identification of CRC and advanced colorectal adenomas in patients enrolled in the national colorectal cancer (CRC) screening program (50-69 year-old) and among who refer to all centers involved in this study for screening colonoscopy with positivity of FIT, of both sex. The primary endpoint of the study is to develop a gut microbiome-based diagnostic tool for the identification of CRC and advanced colorectal adenomas in patients involved in the national CRC screening program, using both statistical and machine learning approaches. The secondary endpoints are:

• The association of clinical and colonoscopy outcomes with FIT results;
• The characterization of gut microbiome from an ecological, taxonomic, phylogenetic and functional point of view;
• The association between microbiome signatures with clinical and colonoscopy outcomes, through statistical and machine-learning algorithms. At baseline, enrolled patients will provide a fecal sample within 2 weeks from enrollment and demographic, clinical characteristics and laboratory data will be recorded. Enrolled patients will be scheduled for colonoscopy, as for clinical practice, within 4 weeks from the positive FIT and histology of resected lesions will be assessed by experienced pathologists according to the WHO classification and the Vienna criteria. Clinical, endoscopic and microbial data will be combined through statistical and machine learning algorithms to identify specific microbial biomarkers associated with CRC and develop a new diagnostic tool, based on a scoring system. This tool will be validated, and its diagnostic performances will be compared with traditional screening methods.

Conditions

Colorectal Cancer

Keywords

microbiome testing; microbiome; colorectal cancer screening; colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Gut microbiome-based diagnostic tool for CRC and advanced colorectal adenomas detection

  Discovery of a gut microbial signature able to predict the diagnosis of colorectal cancer and advanced colorectal adenomas

  60 months

Secondary Outcomes (3)

• Correlation between clinical and endoscopic outcomes with FIT

  60 months

• Microbiome characteristics of fecal samples

  60 months

• Correlation between microbiome signatures with clinical and endoscopic outcomes

  60 months

Study Arms (1)

Groups/Cohorts

Study cohort consists of patients enrolled in the national colorectal cancer (CRC) screening program.Participants will be selected among those enrolled in the nationalcolorectal cancer (CRC) screening program and among who refer to all centers involved in this study for screening colonoscopy. Patients with all inclusion criteria and none of the exclusion criteria will be considered for this study. N=1202 patients will be enrolled, based on sample size calculation and including a validation group. N=911 patients will be needed, and we will add 91 patients to cover a 10% potential drop-out and 200 patients as a validation group (20% of the study cohort).

Diagnostic Test: Gut microbiome testing

Interventions

Gut microbiome testing DIAGNOSTIC_TEST

Gut microbiome testing for the characterization of the patient gut microbiome

Groups/Cohorts

Eligibility Criteria

• Age: 50 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be selected among those enrolled in the national colorectal cancer (CRC) screening program and among who refer to all centers involved in this study for screening colonoscopy. Patients with all inclusion criteria and none of the exclusion criteria will be considered for this study. A total of 1202 patients will be enrolled, based on sample size calculation and including a validation group. N=911 patients will be needed, and we will add 91 patients to cover a 10% potential drop-out and 200 patients as a validation group (20% of the study cohort). Patients enrolled in this validation cohort will have the same exclusion and inclusion criteria of other patients and will undergo the same study procedures.

You may qualify if:

• Patients participating in the national CRC screening program (50-74 years old)
• Positivity to the FIT;
• Ability to provide written informed consent and to be compliant with the study procedures.

You may not qualify if:

• Patients unfit for colonoscopy;
• Other oncological conditions;
• Concomitant severe comorbidities or gastrointestinal (GI) organic diseases (e.g. diverticular disease, inflammatory bowel disease);
• Antibiotics, proton pump inhibitors or probiotics within 4 weeks prior to enrollment.

Sponsors & Collaborators

• Catholic University of the Sacred Heart: lead

Study Sites (1)

Catholic University of the Sacred Heart

Rome, RM, 00168, Italy

RECRUITING

Related Publications (15)

• Pasolli E, Asnicar F, Manara S, Zolfo M, Karcher N, Armanini F, Beghini F, Manghi P, Tett A, Ghensi P, Collado MC, Rice BL, DuLong C, Morgan XC, Golden CD, Quince C, Huttenhower C, Segata N. Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle. Cell. 2019 Jan 24;176(3):649-662.e20. doi: 10.1016/j.cell.2019.01.001. Epub 2019 Jan 17.

  PMID: 30661755 BACKGROUND

• Blanco-Miguez A, Beghini F, Cumbo F, McIver LJ, Thompson KN, Zolfo M, Manghi P, Dubois L, Huang KD, Thomas AM, Nickols WA, Piccinno G, Piperni E, Puncochar M, Valles-Colomer M, Tett A, Giordano F, Davies R, Wolf J, Berry SE, Spector TD, Franzosa EA, Pasolli E, Asnicar F, Huttenhower C, Segata N. Extending and improving metagenomic taxonomic profiling with uncharacterized species using MetaPhlAn 4. Nat Biotechnol. 2023 Nov;41(11):1633-1644. doi: 10.1038/s41587-023-01688-w. Epub 2023 Feb 23.

  PMID: 36823356 BACKGROUND

• Beghini F, McIver LJ, Blanco-Miguez A, Dubois L, Asnicar F, Maharjan S, Mailyan A, Manghi P, Scholz M, Thomas AM, Valles-Colomer M, Weingart G, Zhang Y, Zolfo M, Huttenhower C, Franzosa EA, Segata N. Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3. Elife. 2021 May 4;10:e65088. doi: 10.7554/eLife.65088.

  PMID: 33944776 BACKGROUND

• Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Flejou JF, Geboes K, Hattori T, Hirota T, Itabashi M, Iwafuchi M, Iwashita A, Kim YI, Kirchner T, Klimpfinger M, Koike M, Lauwers GY, Lewin KJ, Oberhuber G, Offner F, Price AB, Rubio CA, Shimizu M, Shimoda T, Sipponen P, Solcia E, Stolte M, Watanabe H, Yamabe H. The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 2000 Aug;47(2):251-5. doi: 10.1136/gut.47.2.251.

  PMID: 10896917 BACKGROUND

• Kaminski MF, Thomas-Gibson S, Bugajski M, Bretthauer M, Rees CJ, Dekker E, Hoff G, Jover R, Suchanek S, Ferlitsch M, Anderson J, Roesch T, Hultcranz R, Racz I, Kuipers EJ, Garborg K, East JE, Rupinski M, Seip B, Bennett C, Senore C, Minozzi S, Bisschops R, Domagk D, Valori R, Spada C, Hassan C, Dinis-Ribeiro M, Rutter MD. Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative. Endoscopy. 2017 Apr;49(4):378-397. doi: 10.1055/s-0043-103411. Epub 2017 Mar 7.

  PMID: 28268235 BACKGROUND

• Thomas AM, Manghi P, Asnicar F, Pasolli E, Armanini F, Zolfo M, Beghini F, Manara S, Karcher N, Pozzi C, Gandini S, Serrano D, Tarallo S, Francavilla A, Gallo G, Trompetto M, Ferrero G, Mizutani S, Shiroma H, Shiba S, Shibata T, Yachida S, Yamada T, Wirbel J, Schrotz-King P, Ulrich CM, Brenner H, Arumugam M, Bork P, Zeller G, Cordero F, Dias-Neto E, Setubal JC, Tett A, Pardini B, Rescigno M, Waldron L, Naccarati A, Segata N. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat Med. 2019 Apr;25(4):667-678. doi: 10.1038/s41591-019-0405-7. Epub 2019 Apr 1.

  PMID: 30936548 BACKGROUND

• Thomas AM, Manghi P, Asnicar F, Pasolli E, Armanini F, Zolfo M, Beghini F, Manara S, Karcher N, Pozzi C, Gandini S, Serrano D, Tarallo S, Francavilla A, Gallo G, Trompetto M, Ferrero G, Mizutani S, Shiroma H, Shiba S, Shibata T, Yachida S, Yamada T, Wirbel J, Schrotz-King P, Ulrich CM, Brenner H, Arumugam M, Bork P, Zeller G, Cordero F, Dias-Neto E, Setubal JC, Tett A, Pardini B, Rescigno M, Waldron L, Naccarati A, Segata N. Author Correction: Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat Med. 2019 Dec;25(12):1948. doi: 10.1038/s41591-019-0663-4.

  PMID: 31664237 BACKGROUND

• Zeller G, Tap J, Voigt AY, Sunagawa S, Kultima JR, Costea PI, Amiot A, Bohm J, Brunetti F, Habermann N, Hercog R, Koch M, Luciani A, Mende DR, Schneider MA, Schrotz-King P, Tournigand C, Tran Van Nhieu J, Yamada T, Zimmermann J, Benes V, Kloor M, Ulrich CM, von Knebel Doeberitz M, Sobhani I, Bork P. Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol Syst Biol. 2014 Nov 28;10(11):766. doi: 10.15252/msb.20145645.

  PMID: 25432777 BACKGROUND

• Wong CC, Yu J. Gut microbiota in colorectal cancer development and therapy. Nat Rev Clin Oncol. 2023 Jul;20(7):429-452. doi: 10.1038/s41571-023-00766-x. Epub 2023 May 11.

  PMID: 37169888 BACKGROUND

• Chan FKL, Wong MCS, Chan AT, East JE, Chiu HM, Makharia GK, Weller D, Ooi CJ, Limsrivilai J, Saito Y, Hang DV, Emery JD, Makmun D, Wu K, Ali RAR, Ng SC. Joint Asian Pacific Association of Gastroenterology (APAGE)-Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia. Gut. 2023 Jul;72(7):1240-1254. doi: 10.1136/gutjnl-2023-329429. Epub 2023 Apr 5.

  PMID: 37019620 BACKGROUND

• Ladabaum U, Dominitz JA, Kahi C, Schoen RE. Strategies for Colorectal Cancer Screening. Gastroenterology. 2020 Jan;158(2):418-432. doi: 10.1053/j.gastro.2019.06.043. Epub 2019 Aug 5.

  PMID: 31394083 BACKGROUND

• Morikawa T, Kato J, Yamaji Y, Wada R, Mitsushima T, Shiratori Y. A comparison of the immunochemical fecal occult blood test and total colonoscopy in the asymptomatic population. Gastroenterology. 2005 Aug;129(2):422-8. doi: 10.1016/j.gastro.2005.05.056.

  PMID: 16083699 BACKGROUND

• Quintero E, Castells A, Bujanda L, Cubiella J, Salas D, Lanas A, Andreu M, Carballo F, Morillas JD, Hernandez C, Jover R, Montalvo I, Arenas J, Laredo E, Hernandez V, Iglesias F, Cid E, Zubizarreta R, Sala T, Ponce M, Andres M, Teruel G, Peris A, Roncales MP, Polo-Tomas M, Bessa X, Ferrer-Armengou O, Grau J, Serradesanferm A, Ono A, Cruzado J, Perez-Riquelme F, Alonso-Abreu I, de la Vega-Prieto M, Reyes-Melian JM, Cacho G, Diaz-Tasende J, Herreros-de-Tejada A, Poves C, Santander C, Gonzalez-Navarro A; COLONPREV Study Investigators. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med. 2012 Feb 23;366(8):697-706. doi: 10.1056/NEJMoa1108895.

  PMID: 22356323 BACKGROUND

• Gupta S, Halm EA, Rockey DC, Hammons M, Koch M, Carter E, Valdez L, Tong L, Ahn C, Kashner M, Argenbright K, Tiro J, Geng Z, Pruitt S, Skinner CS. Comparative effectiveness of fecal immunochemical test outreach, colonoscopy outreach, and usual care for boosting colorectal cancer screening among the underserved: a randomized clinical trial. JAMA Intern Med. 2013 Oct 14;173(18):1725-32. doi: 10.1001/jamainternmed.2013.9294.

  PMID: 23921906 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

For each patient enrolled a stool samples will be collected, using a buffer, to preserve feces at room temperature for up to 48 hours. Fecal samples will be stored at -80°C and will be used for shotgun metagenomics analysis.

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Gianluca Ianiro, MD, PhD

CONTACT

0630159539; gianluca.ianiro@unicatt.it

Serena Porcari, MD, PhD

CONTACT

0630159539; serena.porcari@guest.policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, MD, PhD

Study Record Dates

• First Submitted: December 11, 2024
• First Posted: December 17, 2024
• Study Start: February 7, 2025
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2029
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available after the completion of the study, for 5 years
• Access Criteria: Data will be given upon reasonable request to the PI

Locations

IT (1)