Clinical trial NCT05549336: Single-center, Prospective Cohort Study of PD-1 Inhibitors on Clinical Outcomes of Carotid Plaques in Tumor Patients
Official title: Single-center, Prospective Cohort Study of PD-1inhibitors on Clinical Outcomes of Carotid Plaques in Tumor Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Carotid Artery Plaque
Pd-1 Inhibitors
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2022-09-22
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All tumor patients who are initiating the chemotherapy in The Second Affiliated Hospital, Zhejiang University School of Medicine (SAHZU) and willing to join this cohort study after the date of recruiting (19th Sep 2022). These patients who are eligible for the inclusion criteria would be the targets for further follow-up.

Brief summary: This is a single-center, prospective cohort study on the comparison of clinical outcomes of carotid plaques in PD-1-treated tumor patients vs non-PD-1-treated tumor patients.

Detailed description: Atherosclerosis, a chronic inflammatory disorder, leads to cardio-cerebrovascular diseases, causing most of the global deaths. The chronic and non-resolved inflammatory responses of both innate and adaptive immune cells are involved in the all-stage pathogenesis of atherosclerosis. The impairment of inflammatory resolution promotes atherogenesis and causes instability of atherosclerotic plaques. Their subsequent rupture would induce severe cardio-cerebrovascular incidences (e.g., acute myocardial infarction and ischemic strokes). Recent progress in anti-inflammatory immunotherapies on human atherosclerosis opens the door to resolving this inflammatory disorder by targeting the immune system. However, the impacts of PD-1 immune checkpoint blockades on the progressions of human carotid plaques are not determined yet.

This is a prospective cohort study, which aims to evaluate the effectiveness of PD-1 immune checkpoint blockades on atherosclerotic carotid plaques in tumor patients in comparison to those with non-PD-1-treated tumor patients. The method for quantification and evaluation of atherosclerotic plaques are based on: (1) the mean intima-media thickness of the common carotid artery (Mean CCA thickness); (2) the maximum intima-media thickness of the internal carotid artery (maximum ICA thickness); (3) Carotid plaque areas: by calculation of the plaque area of atherosclerotic plaques on the long axis direction of artery on the ultrasound images. By comparing the above-mentioned parameters at the same location of the carotid artery in the patients when initiating the first dose of anti-PD-1 or non-PD-1 chemotherapy and 3 months after anti-PD-1 or non-PD-1 chemotherapy. It is designed to assess the effectiveness of PD-1 immune checkpoint blockades or non-PD-1 chemotherapy on the clinical prognosis of carotid plaques after a period of 3-month treatment.

Eligibility criteria: Inclusion Criteria:

1. Subjects know about the experiment and signed the informed consent voluntarily; and
2. Subjects are tumor patients and all kinds of tumor diseases of subjects are acceptable; and
3. Subjects are initiating to receive chemotherapy; and
4. Subjects are diagnosed with atherosclerotic carotid plaques by ultrasound examination at the timepoint of the first-dose treatment; and

Exclusion Criteria:

1. Subjects stop receiving or changing the existing chemotherapy during follow-up; or
2. Subjects are reluctant to continue to be involved in this study; or
3. Subjects are known pregnant and lactating women; or
4. Subjects are not complicated with atherosclerotic carotid plaques at the timepoint of the first-dose treatment; or

4. The parameters (e.g., CCA intima-media, ICA intima-media, or carotid plaque area) could not be calculated because of the quality of the ultrasound image; or 5. Other situations that the researchers judged are not suitable for further inclusion.

Primary outcomes:
measure: Carotid plaque area
timeFrame: 3 months
measure: The mean intima-media thickness of the common carotid artery
timeFrame: 3 months
measure: The maximum intima-media thickness of the internal carotid artery
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University, School of Medicine
state: Zhejiang
Study officials:
affiliation: 2nd Affiliated Hospital, School of Medicine at Zhejiang University
name: Jianan Wang, MD, PhD
role: STUDY_CHAIR
affiliation: 2nd Affiliated Hospital, School of Medicine at Zhejiang University
name: Lin Fan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Lorenz MW, Polak JF, Kavousi M, Mathiesen EB, Volzke H, Tuomainen TP, Sander D, Plichart M, Catapano AL, Robertson CM, Kiechl S, Rundek T, Desvarieux M, Lind L, Schmid C, DasMahapatra P, Gao L, Ziegelbauer K, Bots ML, Thompson SG; PROG-IMT Study Group. Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data. Lancet. 2012 Jun 2;379(9831):2053-62. doi: 10.1016/S0140-6736(12)60441-3. Epub 2012 Apr 27.
citation: Spence JD. Measurement of carotid plaque burden. JAMA Neurol. 2015 Apr;72(4):383-4. doi: 10.1001/jamaneurol.2014.3002. No abstract available.
citation: Lechareas S, Yanni AE, Golemati S, Chatziioannou A, Perrea D. Ultrasound and Biochemical Diagnostic Tools for the Characterization of Vulnerable Carotid Atherosclerotic Plaque. Ultrasound Med Biol. 2016 Jan;42(1):31-43. doi: 10.1016/j.ultrasmedbio.2015.09.003. Epub 2015 Oct 20.
citation: Polak JF, Pencina MJ, Pencina KM, O'Donnell CJ, Wolf PA, D'Agostino RB Sr. Carotid-wall intima-media thickness and cardiovascular events. N Engl J Med. 2011 Jul 21;365(3):213-21. doi: 10.1056/NEJMoa1012592.