Clinical trial NCT04476576: Aerobic Exercise is Cardio-protective in Hemato-oncological Disease and New-onset Chemotherapy
Official title: Aerobic Physical Exercise is Cardio-protective in Subjects With Hemato-oncological Disease and New-onset Chemotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Cardiotoxicity
Systolic Dysfunction
Exercise, Aerobic
Keywords: cardiotoxicity
systolic dysfunction
exercise, aerobic
chemotherapy
strain
Lead sponsor: Universidad de la Republica
Sponsor class: OTHER
First posted: 2020-07-20
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Active group: 3 months , 3 times/week aerobic program Control group: 3 months, 3 times/week flexibility program
Primary purpose: PREVENTION

Brief summary: Oncological diseases are the main cause of death in developed countries and also in Uruguay. Advances in therapeutics have made possible to aspire to cure and in other cases long-term remission with a significant increase in survival and the transformation of cancer into a chronic disease. Chemotherapy treatments have some side effects and cardiotoxicity is well known within them. Heart failure (HF) is a progressive pathology, with high mortality and high resource requirements of the health system with a prognosis that may be worse than some types of cancers. The treatment of established systolic dysfunction and symptomatic HF is mainly based on the indication of inhibitors of the angiotensin-converting enzyme and beta-blockers among other pharmaceutical and no pharmaceutical interventions. Aerobic physical exercise, as a therapeutic intervention, reverses the physiopathological changes that are presumed to lead to HF in sedentary people and it is known, it is feasible to execute an exercise program in cancer patients. However, effective treatments for the primary prevention of systolic dysfunction are not well known. Our hypothesis is that an aerobic physical exercise program for at least 3 months, in subjects with lymphoma and new-onset chemotherapy, is effective in preventing left ventricular systolic dysfunction, at the end of chemotherapy and at one year. For this, the investigators propose a randomized, controlled, clinical study which is blind both for the patient and the evaluating physician, comparing the difference of global longitudinal strain (an echocardiographic result of myocardial function) pre-chemotherapy minus end of chemotherapy and minus one year after, between the active group (aerobic program) and the control group (flexibility program).

Detailed description: Hypothesis: an aerobic physical exercise program for at least 3 months, in subjects with hemato-oncological diseases that initiate chemotherapy, is effective in preventing systolic dysfunction of the left ventricle at the end of chemotherapy and one year.

It is a double-blind, randomized controlled trial. Blinded for the subject, evaluating echocardiographic, and treating hematologist.

Blocked randomization method stratified by sex: the randomization sequence will be software generated and centralized by an investigator independent from assistant physicians and echocardiographic evaluator.

To calculate N sample the investigators took a 15% variation of longitudinal left ventricular strain ( clinically significant criteria). The mean and standard deviation of the healthy Uruguayan population was taken from an own study (19.6 ± 1.7%); considering alpha error 0.05 and power 80%, a sample of 16 in each group is required to find significant results. An additional 20% was added for possible "drop outs" resulting in a sample size of 19 subjects/group (N total 38).

The intervention is a 3 months aerobic exercise program compared with a 3 months flexibility exercise program.

The main outcome is the myocardial longitudinal strain variation. Secondary outcomes are related to systolic and diastolic cardiac function, quality of life, cardiac and oncological outcomes, and evaluation of adherence.

Statistical analysis: Qualitative variables will be expressed in absolute and relative frequency. Continuous variables will be resumed as mean and standard deviation or median and interquartile interval regarding normal distribution. Parametric or non- parametric tests of the association will be used regarding test of normality of each continuous outcome and Chi-squared test for the association of qualitative variables. Survival analysis will be made with Kaplan Meier curves and long rank test.

The project is registered in Uruguayan interventional trial registration (Ministery of Public Health) with the number 812559.

Eligibility criteria: Inclusion Criteria:

* Between 18 and 75 years old
* New-onset chemotherapy
* Lymphoma (Hodgkin or non-Hodgkin).

Exclusion Criteria:

* Inability or contraindication to moderate physical activity due to orthopedic cause or general disease (excluding oncological).
* Hemato-oncological pathology different from lymphomas.
* Lymphomas not treated with anthracyclines
* Non-sinus rhythm.
* Poor echocardiographic window (inability to assess longitudinal strain in more than 4 segments).
* Physically active subjects (practice aerobic exercise at least 30 minutes, 3 times / week, 3 previous months).

Primary outcomes:
measure: Change in GLS (exercise of flexibility and balance).
timeFrame: 6 months
Secondary outcomes:
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 1 year
measure: GLS
timeFrame: 1 year
measure: Cardiotoxicity incidense
timeFrame: 1 year
measure: Diastolic function. E/e´index
timeFrame: 1 year
measure: Diastolic function. Left atrial GLS
timeFrame: 1 year
measure: Diastolic function. Left atrial volume.
timeFrame: 1 year
measure: Cardiac injury. Troponin I dosification.
timeFrame: 3 months
measure: Clinical cardiovascular composite outcome
timeFrame: 1 year
measure: Muscle corporal mass
timeFrame: 1 year
measure: Physical activity. Monthly mean of steps.
timeFrame: 3 months
measure: Quality of life. Minnesota LIVING WITH HEART FAILURE® Questionnaire (MLHFQ)
timeFrame: 3 months
measure: Quality of life. Functional Assessment of Cancer Therapy (FACT)
timeFrame: 3 months
measure: Dysnea
timeFrame: 3 months
Other outcomes:
Locations:
city: Montevideo
country: Uruguay
facility: Centro Cardiovascular Universitario-Hospital de Clínicas -FMED- UdelaR
Study officials:
affiliation: Universidad de la Republica
name: Lucia Florio, MD MSc
role: PRINCIPAL_INVESTIGATOR
References: