Clinical trial NCT06518200: Preventing Breast Cancer Therapy-related Cardiovascular Toxicity With a Daily-adapted Program With Mhealth Support
Official title: ATOPE-PRO: Effects on the Prevention of Breast Cancer Therapy-related Cardiovascular Toxicity of a Daily-adapted and Individualized Program With Support From a Mobile Application
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Breast Cancer Female
Keywords: Breast Neoplasms
Cancer therapy-related cardiovascular toxicity
Physical Exercise
Prevention
Quality of life
Rehabilitation
Telemedicine
Health related lifestyle
Lead sponsor: Universidad de Granada
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
name: Hospital Clinico Universitario San Cecilio
First posted: 2024-07-24
Enrollment: 102
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: PREVENTION

Brief summary: ATOPE-PRO, was developed with the intention of consolidating the integration of an innovative system for the prevention of cancer therapy-related cardiovascular toxicity (CTR-CVT) in the continuum care of women with breast cancer in health services. It is a step further towards personalized medicine by optimizing the already available tools and integrating artificial intelligence. Breast cancer survival increases every year, a situation that poses new challenges for health professionals. The European Society for Medical Oncology, a reference in Europe, has just highlighted the need to anticipate to and prevent sequelae derived from the disease and its treatments. This, in addition to having a positive impact on improving the quality of life of people suffering from this disease, would mean a reduction in the risk of recurrence, the appearance of other tumors and other diseases, and death from cancer or other causes, which have a personal impact and represent an overload of the healthcare system. To this end, ATOPE- PRO aims to optimize and refine tools already developed in the previous project (ATOPE, Pl18/01840), integrating artificial intelligence to help identify CTR-CVT, risk profiles, and effective and safe doses (at a clinical level) early on, implementing the program in a longer term, and transferring the results to the social sector (social level). The project has 4 stages: Phase 0 or start-up (to make improvements and analyse usability); Phase 1 for piloting and optimization; Phase 2, to verify efficacy (randomized controlled clinical trial) and Phase 3, in which a deep analysis will be performed and future projects will be conceived.

Detailed description: More and more women are experiencing breast cancer at younger ages, yet survival rates have become very promising. However, years after cancer treatment, related sequelae (physical, psychological, or emotional) may emerge, responsible for post-disease fatalities in many women. The occurrence of these sequelae largely depends on treatment-induced toxicity and individual health status, which is related to lifestyle habits. Among these sequelae, cancer-related cardiovascular toxicity (CTR-CVT) is noteworthy, with an incidence close to 40% in breast cancer, closely linked to treatments such as chemotherapy (especially anthracyclines), targeted therapy (trastuzumab), and radiotherapy (left side or mediastinum), causing DNA and mitochondrial damage. Traditionally defined as a reduction in left ventricular ejection fraction (LVEF) ≥50% in its mildest form, and a decrease in global longitudinal strain (GLS) of \>15% from baseline and/or an increase in cardiac markers (cardiac troponin I or T cTnI/cTnT \>99th percentile, brain natriuretic peptide BNP ≥35 pg/mL, or NT-proBNP ≥125 pg/mL) to severe (requiring inotropic support, mechanical circulatory support, or consideration for transplantation), adding the need for monitoring through various tests, not just LVEF, as it would be too late to detect it. The risk detection of TCVRC is based on medical treatments, which sometimes are insufficient since many patients theoretically considered low-risk develop TCVRC. This has led to the need to study and include other patient-related factors at the time of diagnosis, such as previous presence of cardiovascular diseases, age, lifestyle habits, and comorbidities, to be considered for overall cardiovascular and oncological prognosis and individualized surveillance of TCVRC, along with additional factors that add to the complexity of risk assessment such as cancer type, duration, and doses of oncological treatment. However, the scientific evidence supporting the inclusion of some of these parameters is of questionable quality (level C) and, moreover, they are not usually included in routine assessments, making them less applicable.

To improve the situation and achieve proper prevention of TCVRC, it is necessary to identify parameters with good sensitivity for early detection that can preferably be performed routinely by different healthcare professionals involved in the continuum of care, as well as related risk factors. With this information, the implementation of interventions that could limit treatment interruptions and improve survival after breast cancer would be facilitated. In this context, the European Society of Cardiology Guidelines highlight, in addition to the improvement of detection tools, the inclusion of new parameters, the creation of large data registries, the use of artificial intelligence, or the determination of new risk stratification algorithms, among others.

There is a lack of access to structured physical exercise programs for cancer patients, even though adaptation of exercise to their health status is crucial, as excessive doses could be harmful. Ondulatory exercise prescription may be more suitable for cancer patients, as it allows better adaptation to their health status. So far, one of the systems to achieve this has been prescription based on heart rate variability (HRV) previously used in the sports world and in some cardiovascular pathologies but promising and little studied in the cancer world. However, given the complexity of this disease, its treatments, and the impact it has on different spheres of these patients' health, the inclusion of additional markers is suggested to further optimize personalized exercise programs based on individual needs. With the support of current technologies, monitoring and control of physiological parameters are facilitated, potentially reducing the costs of in-person supervision by healthcare professionals but also the potential health risks in these patients when engaging in physical exercise.

Regarding these interventions, both physical activity and exercise have been recognized as potent multi-effect non-pharmacological therapies in the treatment of TCVRC, although to achieve optimal physiological adaptations and individualization, physical exercise programs must be correctly prescribed. In recent years, interest has shifted towards supervised high-intensity interval exercise, which has been shown to be safe, well-tolerated, effective for TCVRC treatment, and cost-effective. However, most physical exercise programs implemented are general programs with linear prescriptions and questionable adherence. To address adherence issues, physical exercise programs have been combined with behavioral change programs, showing promising short-term results but with loss in the medium/long term. In this regard, the use of technology and patient monitoring, which provide continuous feedback and have proven to be an effective and useful tool for establishing a healthy lifestyle, could offer a solution for both patients and professionals in improving adherence.

ATOPE-PRO aims to integrate into the usual care continuum of women with breast cancer a personalized and individualized mhealth model (ATOPE+ 2.0) for TCVRC prevention, which will allow us to advance towards precision clinical care, to complete its implementation and transfer of results, resulting in an improvement in quality of life, recurrence, and death, meeting the standards requested, through refining and automating the process, ensuring adherence, and offering safe and effective doses of physical exercise.

Eligibility criteria: Inclusion Criteria:

* Recently diagnosed with stage I-III breast cancer
* Treatments predisposing to cardiotoxicity (anthracyclines, targeted therapies, radiotherapy)
* Signed informed consent form
* Medical authorisation to participate
* Smartphone user level

Exclusion Criteria:

* Patient underwent previous cancer treatments.
* Patients were previously diagnosed with cancer
* Pregnant patients. Patients performing other type of therapeutic exercise at diagnosis time with an intake \>or = to 150 moderate-intensity or 75 min of vigorous-intensity a day
* Therapeutic exercise practice not recommended because psychiatric or cognitive disorders or cute or chronic condition that prevents exercise (advanced lung disease, oxygen requirement, stenosis \>70%, metastasis etc.).

Primary outcomes:
measure: Cardiotoxicity
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Systolic function
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
Secondary outcomes:
measure: Number of cardiovascular events
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Comorbidities
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Heart rate variability
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Heart rate
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Blood pressure
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Cardiac damage
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Cardiac Damage
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Endothelial status
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Cardiorespiratory Fitness
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Quadriceps muscle thickness
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Body Fat Mass
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Height
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Weight
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Body Mass Index
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Body Fat Percentage
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Physical Activity level
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Sleep duration
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Fatigue
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Total Cholesterol
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Triglycerides level
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: LDL-C level
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: HDL-C level
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Total antioxidant capacity
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Oxidative status
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Epigenetic profile
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Inflammatory status
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
measure: Immune status
timeFrame: At diagnosis before treatments, after 6 months, and one year after diagnosis.
Other outcomes:
Locations:
city: Granada
country: Spain
facility: University of Granada
Study officials:
affiliation: Universidad de Granada
name: Irene Cantarero Villanueva, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Postigo-Martin P, Penafiel-Burkhardt R, Gallart-Aragon T, Alcaide-Lucena M, Artacho-Cordon F, Galiano-Castillo N, Fernandez-Lao C, Martin-Martin L, Lozano-Lozano M, Ruiz-Vozmediano J, Moreno-Gutierrez S, Illescas-Montes R, Arroyo-Morales M, Cantarero-Villanueva I. Attenuating Treatment-Related Cardiotoxicity in Women Recently Diagnosed With Breast Cancer via a Tailored Therapeutic Exercise Program: Protocol of the ATOPE Trial. Phys Ther. 2021 Mar 3;101(3):pzab014. doi: 10.1093/ptj/pzab014.
citation: Gonzalez-Santos A, Postigo-Martin P, Gallart-Aragon T, Esteban-Cornejo I, Lopez-Garzon M, Galiano-Castillo N, Arroyo-Morales M, Illescas-Montes R, Artacho-Cordon F, Martin-Martin L, Forneiro-Perez R, Lozano-Lozano M, Fernandez-Lao C, Ruiz-Vozmediano J, Sanchez-Salgado C, Cantarero-Villanueva I. Neurotoxicity prevention with a multimodal program (ATENTO) prior to cancer treatment versus throughout cancer treatment in women newly diagnosed for breast cancer: Protocol for a randomized clinical trial. Res Nurs Health. 2021 Aug;44(4):598-607. doi: 10.1002/nur.22136. Epub 2021 May 7.
citation: Postigo-Martin P, Gil-Gutierrez R, Moreno-Gutierrez S, Lopez-Garzon M, Gonzalez-Santos A, Arroyo-Morales M, Cantarero-Villanueva I. mHealth system (ATOPE+) to support exercise prescription in breast cancer survivors: a reliability and validity, cross-sectional observational study (ATOPE study). Sci Rep. 2022 Sep 8;12(1):15217. doi: 10.1038/s41598-022-18706-7.
citation: Gonzalez-Santos A, Lopez-Garzon M, Gil-Gutierrez R, Salinas-Asensio MDM, Postigo-Martin P, Cantarero-Villanueva I. Nonlinear, Multicomponent Physical Exercise With Heart Rate Variability-Guided Prescription in Women With Breast Cancer During Treatment: Feasibility and Preliminary Results (ATOPE Study). Phys Ther. 2023 Sep 1;103(9):pzad070. doi: 10.1093/ptj/pzad070.