Prognostic Value of Neurometabolic Networks in CRC (PVNM-CRC)

NCT06930586 | Recruiting DMC

• 2 other identifiers: ybai2024M752975
• Study Type: observational
• Target: 213
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer (CRC), with annually increasing incidence and mortality worldwide, has become the second leading cause of cancer-related death. The development of CRC often follows the canonical normal-adenoma-carcinoma (N-A-C) sequence driven by progressive accumulation of molecular genetic events, highlighting the importance of early detection and removal of precancerous lesions. However, some patients who have had adenomas removed still have a high risk of developing new adenomas or CRC, especially for those with chronic or systemic disease, indicating that a compositive regulatory network is involved in the tumorigenesis of CRC. Additionally, despite advances in therapeutic strategies having improved the prognosis of CRC patients, tumor metastasis continues to be the predominant cause of mortality. These suggest the need to transcend limitations focusing solely on intertumoral microenvironment or single-timepoint event but adopt a more systemic perspective to elucidate the mechanisms underlying the whole sequence of CRC development and progression. The gastrointestinal (GI) tract comprises a complex ecosystem with extensive interactions between normal or neoplastic epithelial cells with immune, neuronal, and other cell types, as well as microorganisms and metabolites within the gut lumen. Specifically, the intricate relationship between the GI tract and the central nervous system (CNS), collectively known as the brain-gut axis, plays a pivotal role in the pathogenesis of gastrointestinal disorders and neoplasm. For instance, chronic stress increased the risk of colon cancer via activating the COX-2/PEG2 system and promoted tumor cell dissemination by remodeling lymph vasculature. The bidirectional communications of the brain-gut axis are generally found to be mediated by neurotransmitters, inflammatory cytokines, metabolites, or gut microbiota. Nonetheless, the spotlight has shone primarily on the brain-gut crosstalk mechanisms in experimental cellular or animal models, with less attention paid to the structural and functional alterations on the brain networks at the patient level. The evolution of functional neuroimaging modalities and neuroscience technologies has enabled accurate delineation of CNS activities. Specifically, nuclear medicine imaging technology using 2-18F fluoro-2-deoxy-D-glucose (18F-FDG) to adopt whole-body imaging information, is the optimal in vivo method for the investigation of regional human brain metabolism and associations with systemic disorders. We have previously identified the neuronal metabolic-ventricular dyssynchronization axis which might related to major arrhythmic events using myocardial perfusion imaging and the brain 18F-FDG positron emission tomography (PET). Given the potential dual interactions of the brain-gut axis, identification of specific brain regions associated with CRC development and progression might lead to a better understanding of the disease's neurobiological underpinnings and inform the development of targeted therapeutic strategies. Hence, this study was structured to elucidate the role of neuro-metabolism and its potential mediator in regulating CRC tumorigenesis and metastasis. By delving into the neurometabolic-gut axis in CRC, the resulting mechanistic insights might be leveraged to identify diagnostic and prognostic biomarkers and to develop novel therapeutic interventions for CRC patients.

Conditions

Cancer; Brain Injury

Outcome Measures

Primary Outcomes (1)

• Area under curve (AUC)

  AUC is defined as the probability that a randomly chosen positive example is ranked higher than a randomly chosen negative example. A higher AUC indicates a better classification performance of a definite predictor. The AUC is evaluated by calculating the area under curve of receiver operating characteristics (ROC) which plots the proportion of true positive cases (sensitivity) against the proportion of false positive cases (1-specificity) based on various predictive probability threshold. The 95% confidence intervals (95%CI) of AUC are generated by bootstrapping strategy in 1000 sampling times.

  From March 1, 2024 to December 31, 2026-31

Study Arms (1)

Colorectal Cancer

1. Entry Criteria Male/Female subjects with rectal cancer of at least 18 years of age will be enrolled in this trial. 2. Subject Inclusion Criteria In order to be eligible for participation in this trial, the subject must: 1. Be ≥ 18 years of age on day of enrollment. 2. Have pathologically confirmed as rectal adenocarcinoma by electronic colonoscopy biopsy. 3. Have been diagnosed as colorectal cancer (CRC) by enhanced PET/CT. 4. Images of PET/CT sequences are available. 5. Be willing and able to provide written informed assent for Collection and Application of Clinical Sample and Medical Data certified and approved by local ethics committee. Requirements of informed consent for the trial is waived. 6. . Demonstrate adequate organ function as defined.

Eligibility Criteria

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

Study Population

1. Entry Criteria Male/Female subjects with rectal cancer of at least 18 years of age will be enrolled in this trial. 2. Subject Inclusion Criteria In order to be eligible for participation in this trial, the subject must: 2.1. Be ≥ 18 years of age on day of enrollment. 2.2. Have pathologically confirmed as rectal adenocarcinoma by electronic colonoscopy biopsy. 2.3. Have been diagnosed as colorectal cancer (CRC) by enhanced PET/CT. 2.4. Images of PET/CT sequences are available. 2.5. Be willing and able to provide written informed assent for Collection and Application of Clinical Sample and Medical Data certified and approved by local ethics committee. Requirements of informed consent for the trial is waived. 2.6.. Demonstrate adequate organ function as defined in Table 1. All screening labs should be performed within 10 days of treatment initiation.

Male/Female subjects with rectal cancer of at least 18 years of age will be enrolled in this trial.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• The First Affiliated Hospital of Zhengzhou University: lead

Study Sites (1)

PET/CT

Henan, Henan, 450052, China

RECRUITING

Related Publications (4)

• Schledwitz A, Xie G, Raufman JP. Exploiting unique features of the gut-brain interface to combat gastrointestinal cancer. J Clin Invest. 2021 May 17;131(10):e143776. doi: 10.1172/JCI143776.

  PMID: 33998603 BACKGROUND

• Leslie A, Carey FA, Pratt NR, Steele RJ. The colorectal adenoma-carcinoma sequence. Br J Surg. 2002 Jul;89(7):845-60. doi: 10.1046/j.1365-2168.2002.02120.x.

  PMID: 12081733 BACKGROUND

• Murphy CC, Zaki TA. Changing epidemiology of colorectal cancer - birth cohort effects and emerging risk factors. Nat Rev Gastroenterol Hepatol. 2024 Jan;21(1):25-34. doi: 10.1038/s41575-023-00841-9. Epub 2023 Sep 18.

  PMID: 37723270 BACKGROUND

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

  PMID: 38572751 BACKGROUND

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

Neoplasms; Brain Injuries

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Central Study Contacts

Yujie Bai

CONTACT

+8617803883306; baiyujie1010@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: April 16, 2025
• Study Start: March 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: From December 31, 2027 to December 31, 2030-31
• Access Criteria: The subject data (deidentified participant information and PET/CT data) and the full study protocol will be made available to the scientific community, immediately on publication, with as few restrictions as possible. All requests should be submitted to the investigators for consideration. A data use agreement will be required before the release of subject data and institutional review board approval as appropriate.

Locations

CN (1)