Heart FailureHIMALAYASNCT05023785
The HIMALAYAS Trial and Lifestyle Changes in Pediatric, Adolescent and Young Adult Cancer Survivors Study: A Multicentre Randomized Controlled Trial
A study testing Cardio-oncology Rehabilitation (CORE) in people with Heart Failure and Cardiotoxicity, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Pediatric, adolescent and young adult cancer survivors (PAYA-CS) are at higher risk of cardiovascular (CV) morbidity and mortality. This is a consequence of prior cancer-related therapies that have the potential of producing cardiac dysfunction, reducing cardiorespiratory fitness (reduced VO2peak) and psychosocial… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Heart Failure, Cardiotoxicity, Cancer
- What is being tested?
- Cardio-oncology Rehabilitation (CORE)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 336 participants
- Where
- 1 siteCanada
- Study dates
- 1 Jan 2024to Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Be a PAYA-CS, defined as ≤39 years of age at the time of cancer diagnosis;
- Be 18-45 years of age at the time of enrolment;
- Received cancer treatment(s) with known cardiovascular risks (e.g., anthracyclines, trastuzumab, radiotherapy, platinum-based agents, vascular endothelial growth factor inhibitors, tyrosine kinase inhibitors);
- Be cancer-free at the time of enrollment;
- Stage B Heart Failure (SBHF)
- In patients with availability of pre-treatment imaging:
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- ≥10% decrease in LVEF at post-treatment compared to pre-treatment
- ≥15% decrease in GLS at post-treatment compared to pre-treatment
- No pre-treatment imaging:
- LVEF ≤53% in women/51% in men
- GLS >-18%
- Left ventricular hypertrophy (LV mass/body surface area: >95 g/m2 for women or >115 g/m2 for men)
- Concentric remodelling (>0.42 relative wall thickness)
- Diastolic dysfunction (≥ grade 1)
- BNP ≥35pg/ml or NT-proBNP ≥125pg/ml
Who cannot join
- Have an absolute or unresolved relative contraindication to exercise according to the American College of Sports Medicine guidelines;
- Have an untreated physical or mental health concern that precludes safe and effective exercise participation;
- Have established CVD (excluding mildly reduced LVEF as described above);
- Be pregnant at time of recruitment;
- Be currently engaging in frequent high-intensity exercise (>1 high-intensity exercise session per week);
- Have substantial barriers to participating, including (1) living too far from study centre or (2) being unable or willing to comply with the study protocol.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
University Health Network
Toronto, Ontario, M5G2C4
Paaladinesh Thavendiranathan, MD, Dinesh.Thavendiranathan@uhn.ca
About this study
Official title: The Harmonized Interventions to Maintain Health Via Appropriate Risk Factor Modification and Lifestyle Changes in Pediatric, Adolescent and Young Adult Cancer Survivors Study: A Multicentre Randomized Controlled Trial
Pediatric, adolescent and young adult cancer survivors (PAYA-CS) are at higher risk of cardiovascular (CV) morbidity and mortality. This is a consequence of prior cancer-related therapies that have the potential of producing cardiac dysfunction, reducing cardiorespiratory fitness (reduced VO2peak) and psychosocial morbidities (i.e., anxiety and depression). A reduction of physical activity levels can evoke functional limitations resulting in a vicious cycle of reduced exercise tolerance and physical deterioration. To date, there is limited evidence on the use of non-pharmacological strategies such as Cardio-Oncology Rehabilitation (CORE) including structured exercise, behavioural support and risk factor management to improve the outcomes of this underserved population. The HIMALAYAS study is a randomized controlled trial designed to evaluate the impact of a CORE intervention (consisting of six-months home and onsite-based structured moderate to high-intensity aerobic exercise training and CVD risk factor management) on CV and psychosocial health, and the cardiovascular disease risk in PAYA-CS with mild heart dysfunction (stage B heart failure) compared to standard of care (i.e. providing guidance on the current exercise recommendations for cancer survivors). The primary objective of the HIMALAYAS study is to determine whether a six-month supervised CORE intervention, consisting of individualized moderate to high-intensity aerobic exercise training, CVD risk factor modification and enhanced online behavioral support, improves cardiorespiratory fitness (VO2peak; primary outcome), cardiac function, CVD risk factors and biomarkers, and patient-reported outcomes (PROs) at six- months follow-up compared to standard of care (CON) in PAYA-CS with stage B heart failure. The secondary objective is to assess the same outcomes at 12- and 24-months follow-up. We will recruit 336 patients across 5 sites in Canada and upto 134 patients at UHN in 3 years and conclude in 6 years.
Read the detailed description
Over 90,000 North Americans are diagnosed with cancer before the age of 40. Improved cancer therapies have led to an exponential growth in the number of pediatric, adolescent, and young adult cancer survivors (AYA-CS) who are expected to live 50-60 years beyond diagnosis. However, AYA-CS are at increased risk of developing multiple cancer- and treatment-related morbidities including poor fitness (e.g., low VO2peak), hypertension (HTN), diabetes, and poor mental health, which all contribute to premature cardiovascular disease (CVD). The prevalence of CVD events (e.g. heart failure, heart attack, stroke) is up to 23.8% in adult survivors of pediatric cancers with long term follow-up after treatment. The incidence of subclinical CVD, which is a precursor to CVD events, is even higher in AYA-CS; up to 40%, 11%, and 5% experience subclinical cardiomyopathy measured by abnormal global longitudinal strain (GLS), diastolic dysfunction (DD) or mild reduction in left ventricular ejection fraction (LVEF), respectively, and 18% experience reduced aerobic fitness. The treatment of modifiable CVD risk factors must be considered a fundamental target for improving CVD health-related outcomes in AYA-CS. To this end, exercise and best-practices for CVD risk factor modification are integral to a cardiac rehabilitation model. Traditional cardiac rehabilitation models for patients with CVD (consisting of exercise, CVD risk factor treatment, and patient education) are safe and effective in improving HRQoL, morbidity, and mortality risk. However, by virtue of their age and low short-term CVD risk, AYA-CS do not meet traditional criteria for initiating cardiac rehabilitation (CR) and are less likely to receive treatments to reduce CVD risk. AYA-CS with stage B heart failure (SBHF): (1) are at high risk for subsequent HF/CVD death; (2) have lower cardiopulmonary fitness; and (3) are more likely to benefit from CVD risk factor management. Considering that AYA-CS have an estimated 33% prevalence of SBHF, this vulnerable cohort of cancer survivors represent an opportunity for intervention that is highly feasible and potentially impactful. Exercise is a preferred method for optimizing health and survival in PAYA-CS. However, we need models that safely and effectively deliver exercise interventions that meet the unique needs of this population. The cardio-oncology rehabilitation (CORE) model is an intervention that would provide AYA-CS with SBHF a supervised and home-based high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) exercise therapy, CVD risk factor modification, and behavioural support to reduce the risk of CVD. The primary objective of the HIMALAYAS study is to determine whether supervised CORE (Group 1A) improves cardiorespiratory fitness (VO2peak; primary outcome), cardiac function, CVD risk factors and biomarkers, and PROs at 6 months (primary timepoint) as well as 12 and 24 months compared to standard of care group control group (CON) in AYA-CS with SBHF.
The secondary objective of the study is to assess the ongoing behavioural support strategy based on the exercise guidelines for cancer survivors (i.e. 90 to 150 minutes of moderate to vigorous PA per week) on VO2peak, cardiac function, CVD risk factors and biomarkers, and PROs at 24 months compared to standard of care [CON] in AYA-CS with SBHF. Due to the COVID-19 pandemic, CORE intervention will involve a facility-based HIIT session and home-based HIIT session (described as "HIIT at Home") per week.
- Conditions
- Heart Failure, Cardiotoxicity, Cancer
- Being tested
- Cardio-oncology Rehabilitation (CORE)
- Keywords
- Adolescents and Young Adults, Exercise Therapy, Behavioral and Peer Support, Cardiac Rehabilitation, Cancer Survivor
- Medical subject headings
- Heart Failure, Cardiotoxicity, Neoplasms, Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardio-oncology Rehabilitation (CORE)Behavioural
Exercise therapy, CVD risk factor management for the first 6 months (as per current standards in CR models) and behavioural support for the entire 2-year intervention period
| Study group | Role | What they receive |
|---|---|---|
| Cardio-Oncology Rehabilitation (CORE) | Experimental | Participants in the CORE group will have
1. A personalized, supervised exercise program ((in-person at intuition and virtual/ homebased exercises)
2. CV risk factor management,
3. behavioural support for the first 6 months. The behavioural support will continue for CORE participants from months 7-24. Behavioural support includes professionally guided and peer-enhanced exercise behavioural support based on behaviour change stage theories.
CORE participants will be provided a wrist-worn heart and physical activity monitor to use throughout the 24-month observation period. Receives: Behavioral: Cardio-oncology Rehabilitation (CORE) |
| Standard of Care (CON) | No intervention | Participants in the CON group will receive standard medical care and physical activity will be monitored by a wrist-worn activity tracker for 2 years. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiorespiratory fitness
Assessed via cardiopulmonary exercise test and quantified as VO2peak
Measured: Baseline to 6-month follow-up (Primary RCT)
Secondary outcomes (60)
Cardiorespiratory fitness
Assessed via cardiopulmonary exercise test and quantified as VO2peak
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Ventilatory threshold
Estimated using the V-slope method and according to the following criteria: i) an exaggerated response in the volume of carbon-dioxide (i.e., VCO2) relative to the volume of oxygen (i.e., VO2), and ii) the first identifiable break-point in in the minute ventilation (i.e., VE/VO2 vs work rate relationship).
Measured: Baseline to 6-month follow-up (Primary RCT)
Ventilatory threshold
Estimated using the V-slope method and according to the following criteria: i) an exaggerated response in the volume of carbon-dioxide (i.e., VCO2) relative to the volume of oxygen (i.e., VO2), and ii) the first identifiable break-point in in the minute ventilation (i.e., VE/VO2 vs work rate relationship).
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Anaerobic threshold
Estimated according to the three-criterion discrimination technique: i) an excess VCO2 response relative to the VO2 response identified per the modified V-slope criteria; ii) the VE/VO2 to VO2 relationship having been flat or decreasing begins to increase without returning to baseline; and iii) there is no reciprocal decrease in PETCO2 at the point where PETO2 starts to rise systematically.
Measured: Baseline to 6-month follow-up (Primary RCT)
Anaerobic threshold
Estimated according to the three-criterion discrimination technique: i) an excess VCO2 response relative to the VO2 response identified per the modified V-slope criteria; ii) the VE/VO2 to VO2 relationship having been flat or decreasing begins to increase without returning to baseline; and iii) there is no reciprocal decrease in PETCO2 at the point where PETO2 starts to rise systematically.
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Post-exercise heart rate recovery
One-minute HR recovery (HRR; an index of post-exercise parasympathetic reactivation) will be calculated as the HR-difference between peak exercise and following one minute of quiet standing on the treadmill immediately post-test.
Measured: Baseline to 6-month follow-up (Primary RCT)
Post-exercise heart rate recovery
One-minute HR recovery (HRR; an index of post-exercise parasympathetic reactivation) will be calculated as the HR-difference between peak exercise and following one minute of quiet standing on the treadmill immediately post-test.
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Left ventricular ejection fraction (LVEF)
Assessed via 2D and 3D echocardiography
Measured: Baseline to 6-month follow-up (Primary RCT)
Left ventricular ejection fraction (LVEF)
Assessed via 2D and 3D echocardiography
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Global longitudinal strain (GLS)
Assessed via 2D echocardiography
Measured: Baseline to 6-month follow-up (Primary RCT)
Global longitudinal strain (GLS)
Assessed via 2D echocardiography
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Early (E) and late (A) diastolic mitral inflow velocities and deceleration time
Assessed via echocardiography
Measured: Baseline to 6-month follow-up (Primary RCT)
Early (E) and late (A) diastolic mitral inflow velocities and deceleration time
Assessed via echocardiography
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Early diastolic mitral septal and lateral annular velocities (e')
Assessed via tissue Doppler imaging (TDI)
Measured: Baseline to 6-month follow-up (Primary RCT)
Early diastolic mitral septal and lateral annular velocities (e')
Assessed via tissue Doppler imaging (TDI)
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
TR velocity
Assess via spectral Doppler
Measured: Baseline to 6-month follow-up (Primary RCT)
TR velocity
Assess via spectral Doppler
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Left atrial volume
Assess via 2D echocardiography
Measured: Baseline to 6-month follow-up (Primary RCT)
Left atrial volume
Assess via 2D echocardiography
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Diastolic function - E/e' ratio
Calculated using the average of the TDI septal and lateral annular velocities (e')
Measured: Baseline to 6-month follow-up (Primary RCT)
Diastolic function - E/e' ratio
Calculated using the average of the TDI septal and lateral annular velocities (e')
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Left ventricular hypertrophy
Assessed via Devereux formula and quantified as LV mass/body surface area: >95 g/m2 for women or >115 g/m2 for men
Measured: Baseline to 6-month follow-up (Primary RCT)
Left ventricular hypertrophy
Assessed via Devereux formula and quantified as LV mass/body surface area: >95 g/m2 for women or >115 g/m2 for men
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Concentric cardiac remodeling
Assessed as >0.42 relative wall thickness
Measured: Baseline to 6-month follow-up (Primary RCT)
Concentric cardiac remodeling
Assessed as >0.42 relative wall thickness
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Resting heart rate
Measured with an average of 2 readings taken via ECG during the resting period during the cardiac screening procedures.
Measured: Baseline to 6-month follow-up (Primary RCT)
Resting heart rate
Measured with an average of 2 readings taken via ECG during the resting period during the cardiac screening procedures.
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Resting systolic and diastolic blood pressure
Calculated as average of 3 readings measured via automated sphygmomanometer per the Hypertension Canada guidelines.
Measured: Baseline to 6-month follow-up (Primary RCT)
Resting systolic and diastolic blood pressure
Calculated as average of 3 readings measured via automated sphygmomanometer per the Hypertension Canada guidelines.
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Apolipoprotein B
Assessed via blood serum sample
Measured: Baseline to 6-month follow-up (Primary RCT)
Apolipoprotein B
Assessed via blood serum sample
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Total cholesterol
Assessed via blood serum sample
Measured: Baseline to 6-month follow-up (Primary RCT)
Total cholesterol
Assessed via blood serum sample
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Low density lipoprotein
Assessed via blood serum sample
Measured: Baseline to 6-month follow-up (Primary RCT)
Low density lipoprotein
Assessed via blood serum sample
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
High density lipoprotein
Assessed via blood serum sample
Measured: Baseline to 6-month follow-up (Primary RCT)
High density lipoprotein
Assessed via blood serum sample
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Whole body insulin sensitivity
Assessed via Matsuda index
Measured: Baseline to 6-month follow-up (Primary RCT)
Whole body insulin sensitivity
Assessed via Matsuda index
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Hepatic insulin sensitivity
Assessed via homeostasis model assessment insulin resistance (HOMA-IR)
Measured: Baseline to 6-month follow-up (Primary RCT)
Hepatic insulin sensitivity
Assessed via homeostasis model assessment insulin resistance (HOMA-IR)
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Pancreatic beta-cell function
Assessed via the insulin secretion-sensitivity index-2 (ISSI-2)
Measured: Baseline to 6-month follow-up (Primary RCT)
Pancreatic beta-cell function
Assessed via the insulin secretion-sensitivity index-2 (ISSI-2)
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Body mass index
Calculated as body weight (kg) divided by height (m) squared
Measured: Baseline to 6-month follow-up (Primary RCT)
Body mass index
Calculated as body weight (kg) divided by height (m) squared
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Objective physical activity
Objectively assessed via wrist-worn physical activity/heart rate monitor to measure the intensity and duration of all planned and unplanned exercise during the study period
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Subjective physical activity
Subjectively assessed via Godin Leisure Time Physical Activity Questionnaire and reported as moderate-to-vigorous intensity physical activity (MVPA)
Measured: Baseline to 6-month follow-up (Primary RCT)
Subjective physical activity
Subjectively assessed via Godin Leisure Time Physical Activity Questionnaire and reported as moderate-to-vigorous intensity physical activity (MVPA)
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Social support
Measured using the Social Support Survey-Clinical (SSS-C) form, a 5-item survey designed to measure five dimensions of social support + a single item to assess cancer-specific social support.
Measured: Baseline to 6-month follow-up (Primary RCT)
Social support
Measured using the Social Support Survey-Clinical (SSS-C) form, a 5-item survey designed to measure five dimensions of social support + a single item to assess cancer-specific social support.
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Exercise self-efficacy
Measured using the Multidimensional Self-Efficacy for Exercise Scale (MSES) to measure three behavioural subdomains: task, scheduling, and coping
Measured: Baseline to 6-month follow-up (Primary RCT)
Exercise self-efficacy
Measured using the Multidimensional Self-Efficacy for Exercise Scale (MSES) to measure three behavioural subdomains: task, scheduling, and coping
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Anxiety
Measured using the Generalized Anxiety Disorder (GAD-7), a 7-item inventory that assesses 2-week anxiety symptom frequency on a 0-3 scale, with higher scores reflecting higher symptom frequency. A cut-off of ≥10 indicates some degree of clinical anxiety.
Measured: Baseline to 6-month follow-up (Primary RCT)
Anxiety
Measured using the Generalized Anxiety Disorder (GAD-7), a 7-item inventory that assesses 2-week anxiety symptom frequency on a 0-3 scale, with higher scores reflecting higher symptom frequency. A cut-off of ≥10 indicates some degree of clinical anxiety.
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Depression
Measured using the Patient Health Questionnaire (PHQ-9), a 9-item inventory that assesses 2-week depressive symptom frequency on a 0-3 scale, with higher scores reflecting higher symptom frequency. The PHQ-9 has been validated in cancer survivors using a cut-off of ≥8 to indicate some degree of clinical depression.
Measured: Baseline to 6-month follow-up (Primary RCT)
Depression
Measured using the Patient Health Questionnaire (PHQ-9), a 9-item inventory that assesses 2-week depressive symptom frequency on a 0-3 scale, with higher scores reflecting higher symptom frequency. The PHQ-9 has been validated in cancer survivors using a cut-off of ≥8 to indicate some degree of clinical depression.
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Health-related quality of life
Measured using the Medical Outcomes Survey Short-Form (SF-12).
Measured: Baseline to 6-month follow-up (Primary RCT)
Health-related quality of life
Measured using the Medical Outcomes Survey Short-Form (SF-12).
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Health service utilization
Measured using the Health Service Utilization Inventory.
Measured: Baseline to 6-month follow-up (Primary RCT)
Health service utilization
Measured using the Health Service Utilization Inventory.
Measured: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2021
- Study start1 Jan 2024
- Primary completionSep 2026 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 336 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Centre hospitalier de l'Université de Montréal (CHUM), Queen Elizabeth II Health Sciences Centre, Alberta Health services, Vancouver General Hospital, Université de Montréal, Dalhousie University, University of Alberta, University of British Columbia, University of Toronto
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05023785
- Sponsor's protocol ID
- 23-5626
- Acronym
- HIMALAYAS
- Status last verified
- Nov 2025
- First submitted
- 29 Apr 2021
- Last updated
- 26 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Harmonized Interventions to Maintain Health Via Appropriate Risk Factor Modification and Lifestyle Changes in Pediatric, Adolescent and Young Adult Cancer Survivors Study: A Multicentre Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05023785
- Acronym / sponsor ID
- HIMALAYAS / 23-5626
- Conditions
- Heart Failure, Cardiotoxicity, Cancer
- Keywords
- Adolescents and Young Adults, Exercise Therapy, Behavioral and Peer Support, Cardiac Rehabilitation, Cancer Survivor
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 336 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Centre hospitalier de l'Université de Montréal (CHUM), Queen Elizabeth II Health Sciences Centre, Alberta Health services, Vancouver General Hospital, Université de Montréal, Dalhousie University, University of Alberta, University of British Columbia, University of Toronto
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 27 Aug 2021 (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.
Pediatric, adolescent and young adult cancer survivors (PAYA-CS) are at higher risk of cardiovascular (CV) morbidity and mortality. This is a consequence of prior cancer-related therapies that have the potential of producing cardiac dysfunction, reducing cardiorespiratory fitness (reduced VO2peak) and psychosocial morbidities (i.e., anxiety and depression). A reduction of physical activity levels can evoke functional limitations resulting in a vicious cycle of reduced exercise tolerance and physical deterioration. To date, there is limited evidence on the use of non-pharmacological strategies such as Cardio-Oncology Rehabilitation (CORE) including structured exercise, behavioural support and risk factor management to improve the outcomes of this underserved population. The HIMALAYAS study is a randomized controlled trial designed to evaluate the impact of a CORE intervention (consisting of six-months home and onsite-based structured moderate to high-intensity aerobic exercise training and CVD risk factor management) on CV and psychosocial health, and the cardiovascular disease risk in PAYA-CS with mild heart dysfunction (stage B heart failure) compared to standard of care (i.e. providing guidance on the current exercise recommendations for cancer survivors). The primary objective of the HIMALAYAS study is to determine whether a six-month supervised CORE intervention, consisting of individualized moderate to high-intensity aerobic exercise training, CVD risk factor modification and enhanced online behavioral support, improves cardiorespiratory fitness (VO2peak; primary outcome), cardiac function, CVD risk factors and biomarkers, and patient-reported outcomes (PROs) at six- months follow-up compared to standard of care (CON) in PAYA-CS with stage B heart failure. The secondary objective is to assess the same outcomes at 12- and 24-months follow-up. We will recruit 336 patients across 5 sites in Canada and upto 134 patients at UHN in 3 years and conclude in 6 years.
Detailed description
Over 90,000 North Americans are diagnosed with cancer before the age of 40. Improved cancer therapies have led to an exponential growth in the number of pediatric, adolescent, and young adult cancer survivors (AYA-CS) who are expected to live 50-60 years beyond diagnosis. However, AYA-CS are at increased risk of developing multiple cancer- and treatment-related morbidities including poor fitness (e.g., low VO2peak), hypertension (HTN), diabetes, and poor mental health, which all contribute to premature cardiovascular disease (CVD). The prevalence of CVD events (e.g. heart failure, heart attack, stroke) is up to 23.8% in adult survivors of pediatric cancers with long term follow-up after treatment. The incidence of subclinical CVD, which is a precursor to CVD events, is even higher in AYA-CS; up to 40%, 11%, and 5% experience subclinical cardiomyopathy measured by abnormal global longitudinal strain (GLS), diastolic dysfunction (DD) or mild reduction in left ventricular ejection fraction (LVEF), respectively, and 18% experience reduced aerobic fitness. The treatment of modifiable CVD risk factors must be considered a fundamental target for improving CVD health-related outcomes in AYA-CS. To this end, exercise and best-practices for CVD risk factor modification are integral to a cardiac rehabilitation model. Traditional cardiac rehabilitation models for patients with CVD (consisting of exercise, CVD risk factor treatment, and patient education) are safe and effective in improving HRQoL, morbidity, and mortality risk. However, by virtue of their age and low short-term CVD risk, AYA-CS do not meet traditional criteria for initiating cardiac rehabilitation (CR) and are less likely to receive treatments to reduce CVD risk. AYA-CS with stage B heart failure (SBHF): (1) are at high risk for subsequent HF/CVD death; (2) have lower cardiopulmonary fitness; and (3) are more likely to benefit from CVD risk factor management. Considering that AYA-CS have an estimated 33% prevalence of SBHF, this vulnerable cohort of cancer survivors represent an opportunity for intervention that is highly feasible and potentially impactful. Exercise is a preferred method for optimizing health and survival in PAYA-CS. However, we need models that safely and effectively deliver exercise interventions that meet the unique needs of this population. The cardio-oncology rehabilitation (CORE) model is an intervention that would provide AYA-CS with SBHF a supervised and home-based high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) exercise therapy, CVD risk factor modification, and behavioural support to reduce the risk of CVD. The primary objective of the HIMALAYAS study is to determine whether supervised CORE (Group 1A) improves cardiorespiratory fitness (VO2peak; primary outcome), cardiac function, CVD risk factors and biomarkers, and PROs at 6 months (primary timepoint) as well as 12 and 24 months compared to standard of care group control group (CON) in AYA-CS with SBHF.
The secondary objective of the study is to assess the ongoing behavioural support strategy based on the exercise guidelines for cancer survivors (i.e. 90 to 150 minutes of moderate to vigorous PA per week) on VO2peak, cardiac function, CVD risk factors and biomarkers, and PROs at 24 months compared to standard of care [CON] in AYA-CS with SBHF. Due to the COVID-19 pandemic, CORE intervention will involve a facility-based HIIT session and home-based HIIT session (described as "HIIT at Home") per week.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cardio-Oncology Rehabilitation (CORE) | Experimental | Behavioral: Cardio-oncology Rehabilitation (CORE)Participants in the CORE group will have 1. A personalized, supervised exercise program ((in-person at intuition and virtual/ homebased exercises) 2. CV risk factor management, 3. behavioural support for the first 6 months. The behavioural support will continue for CORE participants from months 7-24. Behavioural support includes professionally guided and peer-enhanced exercise behavioural support based on behaviour change stage theories. CORE participants will be provided a wrist-worn heart and physical activity monitor to use throughout the 24-month observation period. |
| Standard of Care (CON) | No intervention | –Participants in the CON group will receive standard medical care and physical activity will be monitored by a wrist-worn activity tracker for 2 years. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Be a PAYA-CS, defined as ≤39 years of age at the time of cancer diagnosis;
- Be 18-45 years of age at the time of enrolment;
- Received cancer treatment(s) with known cardiovascular risks (e.g., anthracyclines, trastuzumab, radiotherapy, platinum-based agents, vascular endothelial growth factor inhibitors, tyrosine kinase inhibitors);
- Be cancer-free at the time of enrollment;
- Stage B Heart Failure (SBHF)
Key exclusion criteria (6 listed)
- Have an absolute or unresolved relative contraindication to exercise according to the American College of Sports Medicine guidelines;
- Have an untreated physical or mental health concern that precludes safe and effective exercise participation;
- Have established CVD (excluding mildly reduced LVEF as described above);
- Be pregnant at time of recruitment;
- Be currently engaging in frequent high-intensity exercise (>1 high-intensity exercise session per week);
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 |
|---|---|---|
| Cardio-oncology Rehabilitation (CORE)Exercise therapy, CVD risk factor management for the first 6 months (as per current standards in CR models) and behavioural support for the entire 2-year intervention period | Behavioural | Cardio-Oncology Rehabilitation (CORE) |
Primary outcome
Cardiorespiratory fitness
Time frame: Baseline to 6-month follow-up (Primary RCT)
Assessed via cardiopulmonary exercise test and quantified as VO2peak
60 secondary outcomes
Cardiorespiratory fitness
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Ventilatory threshold
Time frame: Baseline to 6-month follow-up (Primary RCT)
Ventilatory threshold
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Anaerobic threshold
Time frame: Baseline to 6-month follow-up (Primary RCT)
Anaerobic threshold
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Post-exercise heart rate recovery
Time frame: Baseline to 6-month follow-up (Primary RCT)
Post-exercise heart rate recovery
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Left ventricular ejection fraction (LVEF)
Time frame: Baseline to 6-month follow-up (Primary RCT)
Left ventricular ejection fraction (LVEF)
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Global longitudinal strain (GLS)
Time frame: Baseline to 6-month follow-up (Primary RCT)
Global longitudinal strain (GLS)
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Early (E) and late (A) diastolic mitral inflow velocities and deceleration time
Time frame: Baseline to 6-month follow-up (Primary RCT)
Early (E) and late (A) diastolic mitral inflow velocities and deceleration time
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Early diastolic mitral septal and lateral annular velocities (e')
Time frame: Baseline to 6-month follow-up (Primary RCT)
Early diastolic mitral septal and lateral annular velocities (e')
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
TR velocity
Time frame: Baseline to 6-month follow-up (Primary RCT)
TR velocity
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Left atrial volume
Time frame: Baseline to 6-month follow-up (Primary RCT)
Left atrial volume
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Diastolic function - E/e' ratio
Time frame: Baseline to 6-month follow-up (Primary RCT)
Diastolic function - E/e' ratio
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Left ventricular hypertrophy
Time frame: Baseline to 6-month follow-up (Primary RCT)
Left ventricular hypertrophy
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Concentric cardiac remodeling
Time frame: Baseline to 6-month follow-up (Primary RCT)
Concentric cardiac remodeling
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Resting heart rate
Time frame: Baseline to 6-month follow-up (Primary RCT)
Resting heart rate
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Resting systolic and diastolic blood pressure
Time frame: Baseline to 6-month follow-up (Primary RCT)
Resting systolic and diastolic blood pressure
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Apolipoprotein B
Time frame: Baseline to 6-month follow-up (Primary RCT)
Apolipoprotein B
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Total cholesterol
Time frame: Baseline to 6-month follow-up (Primary RCT)
Total cholesterol
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Low density lipoprotein
Time frame: Baseline to 6-month follow-up (Primary RCT)
Low density lipoprotein
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
High density lipoprotein
Time frame: Baseline to 6-month follow-up (Primary RCT)
High density lipoprotein
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Whole body insulin sensitivity
Time frame: Baseline to 6-month follow-up (Primary RCT)
Whole body insulin sensitivity
Time frame: Baseline to 24-month follow-up (Primary and Secondary RCTs)
Hepatic insulin sensitivity
Time frame: Baseline to 6-month follow-up (Primary RCT)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2025.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cardio-oncology Rehabilitation (CORE) in people with Heart Failure and Cardiotoxicity, run by University Health Network, Toronto at 1 site in Canada.
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 15 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: looking for participants now, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Paaladinesh Thavendiranathan, MD (416-340-5326, dinesh.thavendiranathan@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiorespiratory fitness (time frame: Baseline to 6-month follow-up (Primary RCT)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Nov 2025.