Exercise and Health Counseling in Pediatric Hematopoietic Stem Cell Transplantation

Hematopoietic System--Cancer Clinical Trial

— HENKO  

Official title:

Physical Exercise and Health Counseling in Patients With Pediatric Cancer Patients Undergoing Hematopoietic Stem Cell Transplantation: From Research to Clinical Reality.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06300515
• Other study ID #: PI23/00396
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: Universidad Europea de Madrid
• Contact: Carmen Fiuza-Luces, PhD
• Phone: +34658961509
• Email: cfiuza.imas12[@]h12o.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Thanks to medical advances, survival rates >5 years in children/adolescents undergoing hematopoietic stem cell transplant (HSCT) exceed 70%. However, these patients are at high risk of suffering sequelae associated with the underlying disease and/or the HSCT itself, which negatively affects their physical capacity. These patients also tend to spend too much time inactive, which further accelerates functional decline in addition to producing fatigue and impairing quality of life. Therefore, new strategies are needed to minimize the morbidity associated with HSCT. In this effect, although physical exercise represents an interesting adjuvant treatment option for HSCT, scientific evidence in this area is still scarce. Implementation of physical exercise intervention in pediatric HSCT units is challenging due to the lack of research on the effectiveness, affordability and accessibility of this type of intervention. Therefore, establishing the effectiveness of physical exercise under controlled conditions is an important step. The investigators therefore aim to assess the impact of a physical exercise and health counseling program, compared to health counseling only (control group), in pediatric patients with cancer undergoing HSCT on physical-functional, behavioral, psycho-cognitive and clinical outcomes, and blood biomarkers. The investigators will also determine to what extent the benefits of this intervention are maintained over time. Additionally, the investigators will determine the feasibility of implementing the proposed intervention in a real clinical situation in 3 different pediatric HSCT units.

Description:

Hematopoietic stem cell transplantation (HSCT), which is used to treat high-risk malignancies, as well as some other conditions or even autoimmune processes, consists of several phases: mobilization and subsequent collection of hematopoietic stem cells from the patient (autologous HSCT) or from a donor (allogeneic HSCT); pre-HSCT conditioning; infusion of patient/donor cells; establishment of a new immune and hematopoietic system in the recipient; and prophylaxis/treatment of possible adverse effects. Since the first successful allogeneic transplant was performed in 1968, thanks to the advances experienced in conditioning regimens, as well as in donor-recipient histocompatibility testing, in patient care and in the management of graft versus host disease (GvHD), together with the increase in the number of donors, the expectations of children and adolescents who receive HSCT have improved, achieving long-term survival rates (>5 years) >70%. Yet survivors are at high risk of suffering side effects and toxicities derived from the HSCT itself and/or the underlying disease, with subsequent functional decline. In addition, they show a higher risk of rehospitalization than pediatric cancer survivors who did not receive HSCT and tend to develop chronic pathologies (especially cardiometabolic conditions and frailty) at earlier stages of adulthood than the general population. The investigators therefore aim to assess the impact of a physical exercise and health counseling program, compared to health counseling only (control group), in pediatric patients with cancer undergoing HSCT on the following outcomes assessed at 3 time points [start of hospitalization for HSCT (i.e., baseline), and 8 weeks and 3 months after hospital discharge, respectively]: cardiorespiratory fitness (primary outcome) and ventilatory threshold, muscle strength, left ventricle ejection fraction, fractional shortening and global longitudinal strain, total cardiac mass, functional mobility, adiposity (waist to hip ratio), body mass index, dual-energy X-ray absorptiometry (DXA)-determined body composition (lean and fat mass, bone mineral density), accelerometry-determined physical activity levels, ankle dorsiflexion range of motion, health-related quality of life, cancer-related fatigue, and immune subpopulations. We will also determine clinical outcomes during hospitalization (survival, treatment tolerability, toxicities) as well as molecular biomarkers in blood.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: December 31, 2026
• Est. primary completion date: March 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 21 Years

Eligibility

Inclusion Criteria:

• Age between 4 and 21 years.
• Undergoing hematopoietic stem cell transplantation (HSCT) for cancer diagnosis in complete remission or without remission, in 3 recruiting Hospitals in Madrid
• Undergoing treatment and follow-up in the same hospital.
• Speaking Spanish.
• Providing signed informed consent.

Exclusion Criteria:

• Not being able to participate in the trial according to protocol.
• Comorbidity or acute condition not associated with the diagnosis and that contraindicates the practice of physical exercise, such as severe deficiencies in the locomotor, neurological, cardiovascular and pulmonary systems.
• Serious or chronic medical or psychiatric condition that may increase the risk associated with participation in the trial or that may interfere with the interpretation of the results and, in the opinion of the investigator in discussion with the team, makes having such condition inappropriate for entry to this study; inability to understand the study requirements.
• Not being able to attend hospital visits to perform assessment tests, nor participate in the physical exercise and health counseling program as stipulated in the protocol. Inability to understand the requirements of the study.

Related Conditions & MeSH terms

• Hematopoietic System--Cancer

Intervention

Behavioral:
• Control Group (Active Comparator)
During the intervention phase (hospitalization for HSCT and subsequent 8-week outpatient phase following discharge), the control group will participate in a Health Counseling Program (1 time/week) on aspects related to a healthy lifestyle such as reducing sedentary lifestyle, acquiring healthy nutritional habits, the importance sleep, screen use, and how to address barriers related to clinical status. We will adapt the program to the needs and timing of the patient's treatment, providing the content in one session/week orally (e.g. using presentations) and in writing (e.g. through brochures).
• Intervention Group
Same as Control Group + exercise program as described below: Same as Control Group + exercise program as described below: Hospital ward (during HSCT); and Hospital Gym or online (patients' home) during the outpatient phase. Frequency: 3-5 days/week. Session duration: 30 to 55-60 minutes Aerobic training (5-25 minutes): bicycling, crank-ergometry, circuit-style exercises, and games. Muscle strength training (10-20 minutes): large muscle group exercises (upper/lower limb + trunk exercises) performed as a circuit using body weight or against resistance (against gravity and with body weight, elastic bands, dumbbells, weighted vests, machines), with a wide range of joint mobility and at submaximal/maximum voluntary speed. Inspiratory muscle training will also be performed (5 min daily, using a specific device that creates resistance against inspiration).

Locations

Country	Name	City	State
Spain	Hospital 12 de Octubre	Madrid

Sponsors (5)

Lead Sponsor	Collaborator
Alejandro Lucia	Hospital General Universitario Gregorio Marañon, Hospital Infantil Universitario Niño Jesús, Madrid, Spain, Hospital Universitario 12 de Octubre, Hospital Universitario La Paz

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in objectively-assessed cardiorespiratory fitness (CRF) from baseline to follow-up	CRF assessed as peak oxygen uptake, as determined during a ramp bicycle ergometer test until volitional exhaustion (unit = mL of oxygen/kg body mass/minute),	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Primary	Change in estimated cardiorespiratory fitness (CRF) from baseline to follow-up	CRF estimated with 6-minute walking distance (maximum distance achieved) (unit = meters)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in isometric leg muscle strength from baseline to follow-up	Dynamometer-determined maximal isometric strength of knee flexor muscles (unit = Newtons)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in dynamic lower-limb muscle strength from baseline to follow-up	One-repetition maximum (1RM) during leg press exercise, as estimated from 5RM leg press (unit = kg)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in upper-limb muscle strength from baseline to follow-up	Maximal handgrip strength, mean of 3 attempts with both arms (unit = kg)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in respiratory muscle strength from baseline to follow-up	Maximal inspiratory pressure (unit = mm H20)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in the 'ventilatory threshold' (VT) from baseline to follow-up	Workload eliciting the ventilatory threshold, as determined during the ramp test (unit = watts)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in left ventricle (LV) ejection fraction from baseline to follow-up	Echocardiography-determined LV ejection fraction (unit = percent)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in left ventricle (LV) fractional shortening from baseline to follow-up	Echocardiography-determined LV fractional shortening (unit = percent)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in left ventricle (LV) global longitudinal strain (GLS) from baseline to follow-up	Echocardiography-determined GLS of the LV (unit = percent)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in total cardiac mass from baseline to follow-up	Echocardiography-determined total cardiac mass (unit = grams divided by body surface area (im meters squared)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in functional mobility (stairs test) from baseline to follow-uo	Stairs test (time to walk up and down a 12-step stair) (unit = seconds)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in functional mobility (chair rising) from baseline to follow-up	Sit-stand test (time to stand from a chair 5 times) (unit = seconds)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in functional mobility (Quick Function test) from baseline to follow-up	We will use the Quick Motor Function test, which takes approximately 10 to 15 minutes. An evaluator observes the performance of a patient and scores the 16 items separately on a 5-point ordinal scale (ranging from 0 to 4). If items can be performed on both left and right extremities, the right side is taken. A total score is obtained by adding the scores of all items. The total score ranges between 0 and 64 points (units = points, from 0 to 64)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in body mass index (BMI) from baseline to follow-up	BMI is measured as weight (kg) divided by height squared (m2)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in adiposity index from baseline to follow-up	Waist-to-hip ratio (no units)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in dual-energy X-ray absorptiometry (DXA) measures of total lean mass from baseline to follow-up	DXA-determined total lean mass (grams)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in dual-energy X-ray absorptiometry (DXA) measures of total fat mass from baseline to follow-up	DXA-determined total fat mass (grams)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in dual-energy X-ray absorptiometry (DXA) measures of bone health from baseline to follow-up	DXA-determined bone mineral density (unit = grams/m2)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in physical activity (PA) from baseline to end of treatment	PA levels (moderate/vigorous PA) determined using triaxial accelerometry (unit = minutes/week)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in ankle-dorsiflexion from baseline to end of treatment	Goniometer-determined active and passive ankle range of motion in dorsiflexion (unit = degrees)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in psychological status (health-related quality of life) from baseline to follow-up	Health-related QoL (HRQoL) (Paediatric Quality of Life Inventory [abbreviated as PedsQL 4.0] Cancer Module [3.0], designed to measure paediatric/adolescent cancer specific HRQoL) (unit = 0 to 100 scale, with higher scores indicating better HRQoL)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in psychological status (fatigue) from baseline to follow-up	Cancer-related fatigue (Paediatric Quality of Life (PedsQL 3.0) Multidimensional Fatigue Scale) (0 to 100 score, higher scores meaning higher fatigue)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in lymphocyte subpopulations from baseline to follow-up	Flow-cytometry determined lymphocyte subpopulations (unit = %)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in immune phenotype from baseline to follow-up	Flow-cytometry determined natural killer (NK) cell subsets (unit = %)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in survival from baseline to follow-up	Survival (number of days from diagnosis to the end of the study or death)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in treatment tolerability from baseline to follow-up	Treatment interruption/delay (number of days)	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in treatment toxicities from baseline to follow-up	Common Toxicity Criteria for Adverse Events [CTCAE, global score, 1 (low toxicity) to 5 (highest])	Assessed at three time points: (1) start of hospitalization for HSCT (i.e., baseline); (2) 8 weeks after hospital discharge; and (3) 3 months after hospital discharge (i.e., follow-up)
Secondary	Change in the 'acute' molecular response to a single exercise session from baseline to 8 weeks after hospital discharge	Panel of cytokines/chemokines and peptides (oncostatin-M, osteonectin, FGF21, irisin, follistatin-1, musclin, VEGF-A, fractalkine, interleukin (IL)-8, IL-6 and IL-15 in serum using Luminex® (all assessed in the same units, micrograms/dL) before and after a single exercise training session	Assessed at two time points: (1) start of hospitalization for HSCT (i.e., baseline); and (2) 8 weeks after hospital discharge.
Secondary	Change in the 'chronic' (resting conditions) transcriptome from baseline to 8 weeks after hospital discharge	RNA sequencing (RNAseq) profile in peripheral blood mononuclear cells under resting conditions at baseline and 8 weeks after hospital discharge	Assessed at two time points: (1) start of hospitalization for HSCT (i.e., baseline); and (2) 8 weeks after hospital discharge.
Secondary	Change in the 'acute' transcriptome response to a single exercise session from baseline to 8 weeks after hospital discharge	RNA sequencing (RNAseq) profile in peripheral blood mononuclear cells before and after a single exercise training session	Assessed at two time points: (1) start of hospitalization for HSCT (i.e., baseline); and (2) 8 weeks after hospital discharge.
Secondary	Change in the 'acute' transcriptome response from baseline to 8 weeks after hospital discharge	RNA sequencing (RNAseq) profile in peripheral blood mononuclear cells before and after and exercise training session	Assessed at two time points: (1) start of hospitalization for HSCT (i.e., baseline); and (2) 8 weeks after hospital discharge.