Protection of Cardiovascular Function With Crocin in BrEast Cancer Patients Undergoing Radiotherapy and Chemotherapy

Study Overview
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Brief Summary
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The potential cardiovascular toxicity of tumor treatment and its resulting cardiovascular events have gradually become an important health risk for tumor survivors. Prevention and early identification of cardiovascular toxicity has now become one of the bottlenecks in improving the prognosis of cancer patients. Compared to conventional echocardiographic indicators, new ultrasound technology based on speckle tracking imaging (STI) has shown superiority in the diagnosis, risk stratification and prognosis evaluation of cardiovascular diseases. Crocin, one of the main active components of saffron, has been found protective effect on cardiovascular toxicity in basic studies. This is a randomized, double-blind, placebo-controlled, single-center clinical study to observe the effect of crocin on cardiovascular function caused by breast cancer treatment. One hundred and twenty breast cancer patients planning to undergo radiotherapy or chemotherapy will be included and randomly divided into a crocin group and a placebo group to observe the effect of total saffron tablets on cardiovascular function in patients with early breast cancer radiotherapy and chemotherapy. Participants will take crocin or placebo (4 tablets/time, 3 times a day) during each cycle of chemotherapy for 8 days, started on the 1st day before radiotherapy/chemotherapy. Follow-up was performed every 3 months after enrollment, and the follow-up period was 6 months. Primary study endpoints include the differences between groups in the difference in LVEF and GLS measured by echocardiography at the end of the experiment compared to baseline. Secondary study endpoint include the differences in the incidence rates of serum troponin exceeding the upper limit of normal value and NT-proBNP higher than the normal age reference value, the frequency and duration of chest tightness, chest pain and palpitation, the degree of arrhythmia and ST-T changes displayed by dynamic electrocardiogram, the other echocardiographic parameters (the E/e', global circumferential strain, global radial strain, 3D-GAS, LV torsion, LV rotation/derotation velocity, SDI, RVFWS, and indexes of left ventricular diastolic function and right ventricular function) at the end of the experiment compared to baseline between the two groups.

Official Title
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Protection of Cardiovascular Function With Crocin in BrEast Cancer Patients Undergoing Radiotherapy and Chemotherapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: crocin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age 25-80 years old, female; Patients diagnosed with breast cancer by histopathology; Patients who plan to receive adjuvant radiotherapy/chemotherapy or combined adjuvant trastuzumab or pertuzumab targeted therapy; Patients who completed at least 6 cycles of treatment after enrollment; Exclusion criteria: pregnant or breastfeeding women; Patients with poor echocardiographic image quality; Persistent atrial fibrillation and severe arrhythmia affect the collection and analysis of ultrasound data; Patients who are participating in other clinical studies.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Inclusion criteria: Age 25-80 years old, female; Patients diagnosed with breast cancer by histopathology; Patients who plan to receive adjuvant radiotherapy/chemotherapy or combined adjuvant trastuzumab or pertuzumab targeted therapy; Patients who completed at least 6 cycles of treatment after enrollment; Exclusion criteria: pregnant or breastfeeding women; Patients with poor echocardiographic image quality; Persistent atrial fibrillation and severe arrhythmia affect the collection and analysis of ultrasound data; Patients who are participating in other clinical studies. Eligible patients were randomly divided into 1:1 group and divided into crocin group and placebo control group. Both groups of subjects received crocin or placebo on the basis of standard anti-tumor treatment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crocin group<br>The chemotherapy/radiotherapy protocols are made by oncologists adopted for patients depending on specific conditions , take saffron total glucosides tablets(provided by Reyoung Pharmaceutical Co., Ltd.) for 8 days during each chemotherapy (started on the 1st day before chemotherapy), 4 tablets/time, 3 times a day. | Drug: crocin<br>* Take saffron total glucosides tablets for 8 days during each chemotherapy (started on the 1st day before radiotherapy/chemotherapy), 4 tablets/time, 3 times a day.<br>|
| Placebo Comparator: placebo group<br>Undergoing chemotherapy/radiotherapy protocols as planned, take placebo piece during(the same appearance of crocin tablets, production unit:Reyoung Pharmaceutical Co., Ltd.) for 8 days during each chemotherapy (started on the 1st day before chemotherapy), 4 tablets/time, 3 times a day | Drug: Placebo<br>* Take placebo piece during for 8 days during each chemotherapy (started on the 1st day before radiotherapy/chemotherapy), 4 tablets/time, 3 times a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of LVEF measured by echocardiography | The differences between the two groups in the difference of LVEF measured by Echocardiography at the end of the experiment compared to that at the baseline. | At the end of 6-month follow-up compared to the baseline | 
| The change of GLS measured by echocardiography | The differences between the two groups in the difference of GLS measured by Echocardiography at the end of the experiment compared to that at the baseline. | At the end of 6-month follow-up compared to the baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidences of the increase of serum troponin and/or NT-proBNP | Differences in the incidence rates of serum troponin exceeding the upper limit of normal value and NT-proBNP higher than the normal age reference value between the two groups during follow-up. | During 6 months of following up | 
| The incidences of chest tightness, chest pain and palpitation | The differences in the incidence of chest tightness, chest pain and palpitation between the two groups | During 6 months of following up | 
| The incidences of arrhythmia and ST-T changes | Differences between the two groups in the incidences of arrhythmia and ST-T changes displayed by dynamic electrocardiogram. | During 6 months of following up | 
| The differences of global circumferential strain, global radial strain, global area strain measured by echocardiography. | Differences between groups in the difference in global circumferential strain, global radial strain, global area strain measured by echocardiography at the end of the experiment compared to baseline. | At the end of 6-month follow-up compared to the baseline | 
| The indexes of E, e', a', tricuspid regurgitation velocity measured by echocardiography. | Differences between groups in the difference in the indexes of left ventricular diastolic function measured by echocardiography at the end of the experiment compared to baseline. | At the end of 6-month follow-up compared to the baseline | 
| The indexe of E/e'measured by echocardiography. | Differences between groups in the difference in the indexes of left ventricular diastolic function measured by echocardiography at the end of the experiment compared to baseline. | At the end of 6-month follow-up compared to the baseline | 
| The indexe of left atrial volume index (LAVI)measured by echocardiography. | Differences between groups in the difference in the indexes of left ventricular diastolic function measured by echocardiography at the end of the experiment compared to baseline. | At the end of 6-month follow-up compared to the baseline | 
| The indexe of TAPSE measured by echocardiography. | Differences between groups in the difference in the right ventricular function monitoring indicators measured by echocardiography at the end of the experiment compared to baseline. | At the end of 6-month follow-up compared to the baseline | 
| The indexe of RV fractional area change (FAC) measured by echocardiography. | Differences between groups in the difference in the right ventricular function monitoring indicators measured by echocardiography at the end of the experiment compared to baseline. | At the end of 6-month follow-up compared to the baseline | 
| The indexe of right ventricular free wall global longitudinal strain (RVGLS) measured by echocardiography. | Differences between groups in the difference in the right ventricular function monitoring indicators measured by echocardiography at the end of the experiment compared to baseline. | At the end of 6-month follow-up compared to the baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Cancer therapy-related cardiac dysfunction, Crocin, Echocardiography, Speckle tracking technology