CancerNCT04036032
Role of Aerobic Exercise to Modulate Cardiotoxicity in Long Term Cancer Survivors Exposed to Anthracycline Therapy
An observational study of Cancer and Cardiotoxicity, run by Connecticut Children's Medical Center at 2 sites in United States.
Trial summary
Over 50% of the more than 270,000 childhood cancer survivors in the U.S. have been treated with anthracyclines and thus are at risk of developing cardiotoxicity. The impact of exercise training on LV structure has been extensively studied. Read more about this study
- Who is it for?
- Ages 9 to 99 years
- Conditions the study is for
- Cancer, Cardiotoxicity
- What is being tested?
- Exercise program
- How many people
- 47 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Jun 2015to 27 Aug 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients who are over 9 years of age and who have had anthracycline chemotherapy treatments that were completed over 2 years ago will be asked to participant in the study. Patients from the oncology clinic and the Stars clinic will be asked to participate.
Who may be able to join
- Long-term childhood cancer survivors greater than 9 years of age*
- Exposed to anthracycline chemotherapy * Age > 9 years of age was chosen to avoid the need for general anesthesia or sedation
Who cannot join
- Contraindications to CMRI*
- Individuals needing sedation to complete the cMRI
- Subject not able to perform stress test.
- Pregnancy**
- Non-English speaking individuals
- Orbital X-Ray confirmed to have metal in the eye or patient confirmed to have metal in the eye
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Nationwide Children's Hospital
Columbus, Ohio, 43205
CT Children's Medical Center
Hartford, Connecticut, 06106
About this study
Over 50% of the more than 270,000 childhood cancer survivors in the U.S. have been treated with anthracyclines and thus are at risk of developing cardiotoxicity. The impact of exercise training on LV structure has been extensively studied. Left ventricular hypertrophy and cardiac chamber enlargement with the accompanying ability to generate a large stroke volume are direct results of exercise training. Aerobic exercise therapy offers a non-pharmacological mechanism to modulate multiple gene expression pathways that may promote cardiac remodeling. No prior studies have investigated the efficacy of aerobic exercise in the prevention or treatment of anthracycline-induced cardiotoxicity. We hypothesize that exercise intervention leads to a reverse in adverse cardiac remodeling with improvement of global and regional myocardial function in patients exposed to anthracycline.
Read the detailed description
The goal of this research is to assess the effect of exercise intervention on imaging parameters by CMR, cardiopulmonary indices and MicroRNA expression in survivors of childhood cancer exposed to anthracycline therapy. Thus, results from this study could provide a foundation for a paradigm shift in our approach to the prevention and management of anthracycline induced cardiotoxicity in this population. Patients who have been exposed to anthracycline treatment and who are greater than 9 years of age will be enrolled.
Patients will come into the clinic for 7 study visits. Patients will have an exercise intervention provided to them by a trainer at the designated YMCA. Patients will start their exercise for 15 minutes per day for 3-5 days a week for week one progressing to 45 minutes per day, 3 - 5 days a week as tolerated by the end of week four. The goal during each session is for the patient to exercise at 50-80% of their age adjusted maximum heart rate, which will be determined by the personal trainer (PT) at their initial visit. The exercise program will continue for 12 weeks (ending at 16 weeks after entry to the study).
In the clinic patients will have the following tests completed:
Week 0 and Week 16: Cardiac MRI, stress test along with blood samples and Karnofsky/Lansky Scale.
Week 0 patients receive a Fitbit and home diary/Wellness Log for completion. Week 4 began exercise intervention Weeks 0, 4, 8, 16 and 20 patients will receive phone calls for symptom tracker Weeks 0, 16, and 6 month f/u patients complete a questionnaire
Patients will also have Fitness assessments to see how their exercise intervention is doing.
Specific Aim 1: To measure the impact of the toolbox exercise intervention on cardiac remodeling as measured by cardiac magnetic resonance Imaging (CMR) in childhood cancer survivors exposed to Anthracycline therapy. The objective of this Aim is to use CMR to characterize changes of myocardial mass, volume, global and regional myocardial function at baseline and following exercise intervention.
Specific Aim 2a: To examine the impact of the toolbox exercise intervention on exercise testing derived cardiopulmonary parameters in childhood cancer survivors exposed to Anthracycline therapy. The objective of this aim is to assess changes in oxygen consumption (peak VO2), VO2 @ anaerobic threshold, O2 pulse, and he ventilation/carbon dioxide slope (VE/VCO2slope) at baseline and following exercise intervention.
Specific Aim 2b: To examine the impact of the toolbox exercise intervention on quality of life, functional status and fitness in childhood cancer survivors exposed to anthracycline therapy. his Aim will test the hypothesis that exercise intervention will result in improvement in:
- Quality of life as measured by PedsQL 4.0 for children ≤ 18 and the SF-36 for adults > 18
- Patient functional status as measured by the Karnofsky/Lansky Scale
- Fitness as measured by range of motion, balance, endurance, body composition and and functional strength
Specific Aim 3: Analyze serum microRNA (miRNA) expression focusing on cardiac stress signaling pathways at three time points during each stress test: at baseline (prior to stress testing), immediately post-exercise (within 1min of completion of exercise testing), and after 1 hour of rest following stress testing). The objective of this aim is to measure changes in microRNA expression in plasma related to stress signaling pathways after exercise intervention when compared to baseline
- Conditions
- Cancer, Cardiotoxicity
- Being tested
- Exercise program
- Medical subject headings
- Neoplasms, Cardiotoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise programOther
Encourage to work out 4 to 5 times a week for 3 months. Patient chooses what exercise they would like to do. At YMCA visit for fitness assessments they provide exercise support
What is being measured
The primary outcome is the main question the study is designed to answer.
Small increase in the left and right ventricular volume
Small increase in the left and right ventricular volume
Measured: Baseline to Week 12
Small increase in left and right ventricular mass
Small increase in left and right ventricular mass
Measured: Baseline to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2019
- Study start19 Jun 2015
- Primary completion27 Aug 2025
- Study completion27 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Connecticut Children's Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Nationwide Children's Hospital
- Responsible party
- Principal investigator, Tiffany Ruiz, Connecticut Children's Medical Center
- Investigators
- Tiffany L Berthod (Ruiz), MSN, RN, CPN, CCRC, Principal investigator, Connecticut Children's Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04036032
- Sponsor's protocol ID
- 14-110
- Status last verified
- Oct 2025
- First submitted
- 25 Jul 2019
- Last updated
- 14 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Pending information from PI
Publications
Toro-Salazar OH, Pescatello LS, Mah ML, Wilhelm C, Orsey AD, Berthod T, Mosha MH, Brimacombe M, Fan T, Wanner C, Slawinski M, Hor KN. A pilot exercise intervention to evaluate the role of cardiorespiratory fitness in modulating cardiotoxicity among childhood cancer survivors exposed to anthracycline therapy. Cardiooncology. 2025 Oct 9;11(1):88. doi: 10.1186/s40959-025-00388-5.
PubMed 41068874
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Aerobic Exercise to Modulate Cardiotoxicity in Long Term Cancer Survivors Exposed to Anthracycline Therapy
- ClinicalTrials.gov ID
- NCT04036032
- Acronym / sponsor ID
- 14-110
- Conditions
- Cancer, Cardiotoxicity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Connecticut Children's Medical CenterUniversity, hospital or other
- Collaborators
- Nationwide Children's Hospital
- Study start
- 19 Jun 2015 (actual)
- Primary completion
- 27 Aug 2025 (actual)
- Study completion
- 27 Aug 2025 (actual)
- First posted
- 29 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Over 50% of the more than 270,000 childhood cancer survivors in the U.S. have been treated with anthracyclines and thus are at risk of developing cardiotoxicity. The impact of exercise training on LV structure has been extensively studied. Left ventricular hypertrophy and cardiac chamber enlargement with the accompanying ability to generate a large stroke volume are direct results of exercise training. Aerobic exercise therapy offers a non-pharmacological mechanism to modulate multiple gene expression pathways that may promote cardiac remodeling. No prior studies have investigated the efficacy of aerobic exercise in the prevention or treatment of anthracycline-induced cardiotoxicity. We hypothesize that exercise intervention leads to a reverse in adverse cardiac remodeling with improvement of global and regional myocardial function in patients exposed to anthracycline.
Detailed description
The goal of this research is to assess the effect of exercise intervention on imaging parameters by CMR, cardiopulmonary indices and MicroRNA expression in survivors of childhood cancer exposed to anthracycline therapy. Thus, results from this study could provide a foundation for a paradigm shift in our approach to the prevention and management of anthracycline induced cardiotoxicity in this population. Patients who have been exposed to anthracycline treatment and who are greater than 9 years of age will be enrolled.
Patients will come into the clinic for 7 study visits. Patients will have an exercise intervention provided to them by a trainer at the designated YMCA. Patients will start their exercise for 15 minutes per day for 3-5 days a week for week one progressing to 45 minutes per day, 3 - 5 days a week as tolerated by the end of week four. The goal during each session is for the patient to exercise at 50-80% of their age adjusted maximum heart rate, which will be determined by the personal trainer (PT) at their initial visit. The exercise program will continue for 12 weeks (ending at 16 weeks after entry to the study).
In the clinic patients will have the following tests completed:
Week 0 and Week 16: Cardiac MRI, stress test along with blood samples and Karnofsky/Lansky Scale.
Week 0 patients receive a Fitbit and home diary/Wellness Log for completion. Week 4 began exercise intervention Weeks 0, 4, 8, 16 and 20 patients will receive phone calls for symptom tracker Weeks 0, 16, and 6 month f/u patients complete a questionnaire
Patients will also have Fitness assessments to see how their exercise intervention is doing.
Specific Aim 1: To measure the impact of the toolbox exercise intervention on cardiac remodeling as measured by cardiac magnetic resonance Imaging (CMR) in childhood cancer survivors exposed to Anthracycline therapy. The objective of this Aim is to use CMR to characterize changes of myocardial mass, volume, global and regional myocardial function at baseline and following exercise intervention.
Specific Aim 2a: To examine the impact of the toolbox exercise intervention on exercise testing derived cardiopulmonary parameters in childhood cancer survivors exposed to Anthracycline therapy. The objective of this aim is to assess changes in oxygen consumption (peak VO2), VO2 @ anaerobic threshold, O2 pulse, and he ventilation/carbon dioxide slope (VE/VCO2slope) at baseline and following exercise intervention.
Specific Aim 2b: To examine the impact of the toolbox exercise intervention on quality of life, functional status and fitness in childhood cancer survivors exposed to anthracycline therapy. his Aim will test the hypothesis that exercise intervention will result in improvement in:
- Quality of life as measured by PedsQL 4.0 for children ≤ 18 and the SF-36 for adults > 18
- Patient functional status as measured by the Karnofsky/Lansky Scale
- Fitness as measured by range of motion, balance, endurance, body composition and and functional strength
Specific Aim 3: Analyze serum microRNA (miRNA) expression focusing on cardiac stress signaling pathways at three time points during each stress test: at baseline (prior to stress testing), immediately post-exercise (within 1min of completion of exercise testing), and after 1 hour of rest following stress testing). The objective of this aim is to measure changes in microRNA expression in plasma related to stress signaling pathways after exercise intervention when compared to baseline
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 9 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients who are over 9 years of age and who have had anthracycline chemotherapy treatments that were completed over 2 years ago will be asked to participant in the study. Patients from the oncology clinic and the Stars clinic will be asked to participate.
Key inclusion criteria (2 listed)
- Long-term childhood cancer survivors greater than 9 years of age*
- Exposed to anthracycline chemotherapy * Age > 9 years of age was chosen to avoid the need for general anesthesia or sedation
Key exclusion criteria (6 listed)
- Contraindications to CMRI*
- Individuals needing sedation to complete the cMRI
- Subject not able to perform stress test.
- Pregnancy**
- Non-English speaking individuals
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise programEncourage to work out 4 to 5 times a week for 3 months. Patient chooses what exercise they would like to do. At YMCA visit for fitness assessments they provide exercise support | Other | – |
Primary outcome
Small increase in the left and right ventricular volume
Time frame: Baseline to Week 12
Small increase in the left and right ventricular volume
Small increase in left and right ventricular mass
Time frame: Baseline to Week 12
Small increase in left and right ventricular mass
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2025.
- Derived from this study: PubMed 41068874Toro-Salazar OH, Pescatello LS, Mah ML, Wilhelm C, Orsey AD, Berthod T, Mosha MH, Brimacombe M, Fan T, Wanner C, Slawinski M, Hor KN. A pilot exercise intervention to evaluate the role of cardiorespiratory fitness in modulating cardiotoxicity among childhood cancer survivors exposed to anthracycline therapy. Cardiooncology. 2025 Oct 9;11(1):88. doi: 10.1186/s40959-025-00388-5.
- Individual participant dataSharing planned: Undecided. Pending information from PI
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tiffany L Berthod (Ruiz), MSN, RN, CPN, CCRC principal investigator
Connecticut Children's Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cancer and Cardiotoxicity, run by Connecticut Children's Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Small increase in the left and right ventricular volume (time frame: Baseline to Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04036032, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2025.