A Novel Approach Utilizing Organ Specific Age Proteomics

NCT ID: NCT06789653

Last Updated: 2025-01-28

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-10-10
• Study Completion Date: 2026-08-01

Brief Summary

This study compares changes in P16INK4A expression and plasma proteomic signatures of specific organ age pre- and post-chemotherapy in women treated with adjuvant chemotherapy for early-stage breast cancer. It aims to determine if biological and accelerated immune aging, assessed using T cells from peripheral blood, represents aging in different organs.

Patients receiving chemotherapy, especially adjuvant regimens that include anthracyclines and taxanes, often experience late development of cardiac toxicity, functional loss, and cognitive decline. Comparing baseline characteristics with organ aging before therapy might identify patients at the highest risk for chemotherapy complications. For example, this is clinically significant for patients whose therapy includes taxanes or other drugs known to cause peripheral neuropathy. Identifying aging in the neurological or vascular systems before treatment might lead to changes in regimens.

Determining accelerated aging in specific organs allows for investigating interventions to mitigate organ damage. For instance, identifying patients at the highest risk of cardiac aging after treatment could lead to testing the effects of exercise, senolytics, and other strategies to reduce the risk of long-term heart disease.

Detailed Description

Chemotherapy has revolutionized cancer treatment, significantly improving relapse-free and survival rates for many cancers. However, these advances have come with a downside, and nowhere is this more evident than in childhood cancer. Despite the significant advances in the curability of most childhood cancers, up to 20% of patients die of comorbidity and secondary cancers by the age of 35 years.

Recent research shows that a plasma proteomic measure of protein abundance and expression can provide a" global" proteomic signature that accurately predicts chronologic age in the general population. It was shown that accelerated organ aging conferred a 20-50% higher mortality risk, and this was pronounced for those with accelerated cardiac and brain aging.

Previous studies have shown that p16INK4a, a robust biomarker of cell senescence measured in peripheral blood T cells, rises dramatically and likely irreversibly after adjuvant therapy for breast cancer. For anthracycline regimens, p16INK4a changes suggest 10 to 20 years of accelerated aging shortly after treatment. Additionally, in murine models, changes in P16INK4A are seen in all organs as mice age, but not all organs age at the same rate.

Conditions

Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Chemotherapy

40 patients with early-stage breast cancer whose treatment plan includes adjuvant or neoadjuvant chemotherapy.

p16INK4a mRNA level assessment

Intervention Type: DIAGNOSTIC_TEST

Blood samples will be collected at two time points, plasma samples will be aliquoted, and T cells will be separated and expression of p16INK4a mRNA in peripheral blood T-lymphocytes will be determined

organ-specific protein signatures assessment

Intervention Type: DIAGNOSTIC_TEST

Blood samples will be collected at two time points, plasma samples will be aliquoted, and organ-specific protein signatures assessment will be determined.

Control

20 patients with early-stage breast cancer whose treatment plan does not includeadjuvant or neoadjuvant chemotherapy.

p16INK4a mRNA level assessment

Intervention Type: DIAGNOSTIC_TEST

Blood samples will be collected at two time points, plasma samples will be aliquoted, and T cells will be separated and expression of p16INK4a mRNA in peripheral blood T-lymphocytes will be determined

organ-specific protein signatures assessment

Intervention Type: DIAGNOSTIC_TEST

Blood samples will be collected at two time points, plasma samples will be aliquoted, and organ-specific protein signatures assessment will be determined.

Interventions

p16INK4a mRNA level assessment

Blood samples will be collected at two time points, plasma samples will be aliquoted, and T cells will be separated and expression of p16INK4a mRNA in peripheral blood T-lymphocytes will be determined

Intervention Type: DIAGNOSTIC_TEST

organ-specific protein signatures assessment

Blood samples will be collected at two time points, plasma samples will be aliquoted, and organ-specific protein signatures assessment will be determined.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Age ≥22years and <66 years
• Diagnosed with early-stage breast cancer (The American Joint Committee on Cancer stages I-III).
• Understand and read English.
• Receive care at the study site.
• Able to understand and participate in study procedures for length of study.

Exclusion Criteria

• Unable to provide consent, unable to communicate verbally.
• Unable to understand or read English.
• Enrolled in hospice care.

• Minimum Eligible Age: 22 Years
• Maximum Eligible Age: 66 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hyman Muss, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Allison Ross

Role: CONTACT

allison_ross@med.unc.edu

919-966-3856

Facility Contacts

Allison Rose

Role: primary

allison_ross@med.unc.edu

919-974-0000

Related Links

http://unclineberger.org/patientcare/clinical-trials/clinical-trials

Clinical trials at UNC Lineberger

Other Identifiers

LCCC2435

Identifier Type: -

Identifier Source: org_study_id