Improving bone health in paediatric cancer survivors through exercise

ISRCTN	ISRCTN61195625
DOI	https://doi.org/10.1186/ISRCTN61195625
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	LCF/ BO/PR19/11700007
Sponsor	University of Granada
Funders	“la Caixa” Foundation, Ministerio de Ciencia e Innovación

Submission date: 27/03/2020
Registration date: 02/04/2020
Last edited: 19/09/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Despite a 13% increase in childhood cancer incidence over the last 40 years, the 5-year survival rate has now been set up at 80%. However, curing cancer has important consequences. One of the most common issues in paediatric cancer survivors is a reduction of the bone mineral density. Recent evidence highlights the survivorship phase (rather than the treatment one) for performing interventions to improve bone health. Exercise can improve bone health in healthy children; however, this effect has not been studied yet in this population.
This intervention will analyse the influence of a 9-month exercise intervention on bone mass in growing paediatric cancer survivors.

Who can participate?
Paediatric cancer survivors 6 to 18 years of age at recruitment, ≥1 year from diagnosis and not currently receiving treatment for cancer.

What does the study involve?
Participants will be randomly allocated to the intervention or control group. The intervention will involve a combination of strength and jumping activities. Likewise, the intervention will aim to improve muscular fitness before implementing mechanical loading through jumping exercises. This exercise program will be completed at home and delivered through an online platform. The control group will not perform the exercise program, but they will be offered the same program at the end of the intervention. Nutritional and sun exposure counselling will also be given to both groups.

What are the possible benefits and risks of participating?
The main expected benefit of participating in this study is the improvement in bone mass which lowers the risk of having future bone diseases, such as osteoporosis. The risks of participating are similar to those derived from exercise practice.

Where is the study run from?
1. Virgen de las Nieves Hospital (Spain)
2. Reina Sofía Hospital (Spain)

When is the study starting and how long is it expected to run for?
May 2020 to January 2023

Who is funding the study?
1. “la Caixa” Foundation (Spain)
2. Ministry of Science and Innovation (Spain)

Who is the main contact?
Dr Luis Andrés Gracia Marco, lgracia@ugr.es

Contact information

Dr Luis Andrés Gracia Marco
Public

Pasaje de la Ciencia 1
Granada
18016
Spain

ORCID ID	0000-0002-4020-0256
Phone	+34 689 205 924
Email	lgracia@ugr.es

Study information

Primary study design	Interventional
Study design	Interventional randomized controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Effect of an online exercise program on bone health in paediatric cancer survivors
Study acronym	iBoneFIT
Study objectives	A 9-month plyometric-exercise intervention improves bone health in paediatric cancer survivors
Ethics approval(s)	Approved 10/01/2020, Review Committee for Research Involving Human Subjects of Andalucía (Comite de Etica de Investigación de Cordoba. Avda. Menéndez Pidal s/nº 14004-Córdoba, Spain; no tel. provided; no email provided), ref: 4500
Health condition(s) or problem(s) studied	Paediatric cancer survivors at risk of endocrine dysfunction
Intervention	iBoneFIT is a multicentre randomized controlled trial. Participants will be allocated into two groups: an intervention group (a 9-month exercise intervention) and a control group (no exercise program for 9 months; updated 11/08/2020: no exercise intervention). Specific dietary advice regarding calcium and vitamin D will be given to both groups. Simple randomization will be applied using an online tool. Intervention group: The program will be delivered via an online platform. Nutritional and sun exposure counselling will also be given. The 9-month intervention will involve 3 to 4 days/week of a home-based jumping programme. The jumping programme takes approximately 10 min/day and all activities will be performed on hard surfaces. In brief, the jumping intervention will consist of 3 stages and the volume of each stage will increase progressively. In stage 1 (2 months), participants will perform body mass-based squats; in stage 2 (3 months), participants will perform squat jumps; in stage 3 (4 months), participants will perform countermovement jumps. Furthermore, five behavior change techniques were used to increase participants’ engagement (i.e. action planning and goal setting, provide instructions and demonstrations of how to perform the behavior, self-monitoring of behavior, provide feedback on performance and information about health consequences). Likewise, a gamification design (i.e. points, rankings and rewards) was included to improve the interest, incentive and purposiveness of this non-game program. Control group: no exercise program will be delivered. At the end of the intervention, the exercise program will be offered to all participants in the control group. Educational advice and leaflets about the importance of healthy lifestyles, nutrition and sun exposure will be given to both groups on a monthly basis.
Intervention type	Behavioural
Primary outcome measure(s)	Current primary outcome measures as of 20/06/2022: 1. Bone mineral density measured using Dual-energy X-ray Absorptiometry (DXA) at baseline and post-intervention 2. Bone architecture and geometry measured using specific software for Hip Structural Analysis at baseline and post-intervention 3. Spine Trabecular Bone Score measured using the software iNsight at baseline and post-intervention 4. Volumetric bone parameters measured using the software 3D-SHAPER at baseline and post-intervention Previous primary outcome measures from 11/08/2020 to 20/06/2022: 1. Bone mineral density measured using Dual-energy X-ray Absorptiometry (DXA) at baseline, post-intervention and follow-up (4 months post-intervention) 2. Bone architecture and geometry measured using specific software for Hip Structural Analysis at baseline, post-intervention and follow-up (4 months post-intervention) 3. Spine Trabecular Bone Score measured using the software iNsight at baseline, post-intervention and follow-up (4 months post-intervention) 4. Volumetric bone parameters measured using the software 3D-SHAPER at baseline, post-intervention and follow-up (4 months post-intervention) Previous primary outcome measures: 1. Bone mineral density measured using Dual-energy X-ray Absorptiometry (DXA) at baseline, post-intervention and follow-up (4 months post-intervention) 2. Bone architecture and geometry using specific software for Hip Structural Analysis Trabecular Bone Score at baseline, post-intervention and follow-up (4 months post-intervention)
Key secondary outcome measure(s)	Current secondary outcome measures as of 20/06/2022: 1. Anthropometric measurements measured using an electronic scale for body mass and a precision stadiometer for body height (body mass index is also calculated). Body composition measured using DXA and a bioimpedance scale. Additionally, somatic maturation measured using the prediction of years from peak height velocity using validated algorithms for children. All of these parameters are assessed at baseline and post-intervention. 2. Physical fitness measured using the ALPHA fitness test battery at baseline and post-intervention. In addition, perceived physical fitness measured by the International Fitness Scale 3. Physical activity and sedentarism measured using tri-axial accelerometers at baseline and post-intervention. Furthermore, these variables are measured using the Youth Activity Profile questionnaire. Additionally, the influence of previous physical activities on bone is measured using the bone-specific physical activity questionnaire. 4. Calcium intake measured using a food-frequency questionnaire at baseline and post-intervention. Vitamin D status measured using the vitamin D questionnaire at baseline and post-intervention 5. Biochemical markers measured using venous blood samples between 8:00 and 10:00 after an overnight fast at baseline and post-intervention 6. Psychological distress measured using State-Trait Anxiety Inventory for Children (STAIC-T), Children Depression Inventory (CDI) and Positive Affect Schedule for children (PANAS-C) at baseline and post-intervention 7. Well-being measured using Subjective Happiness Scale (SHS), Life Orientation Test-Revised (LOT-R) and Positive Affect Schedule for children (PANAS-C) at baseline and post-intervention 8. Quality of life measured using the Paediatric Quality of Life Inventory (PedsQLTM 4.0 Generic Core Scales) at baseline and post-intervention Previous secondary outcome measures from 11/08/2020 to 20/06/2022: 1. Anthropometric measurements measured using an electronic scale for body mass and a precision stadiometer for body height (body mass index is also calculated). Body composition measured using DXA and a bioimpedance scale. Additionally, somatic maturation measured using the prediction of years from peak height velocity using validated algorithms for children. All of these parameters are assessed at baseline, post-intervention and follow-up (4 months post-intervention). 2. Physical fitness measured using the ALPHA fitness test battery at baseline, post-intervention and follow-up (4 months post-intervention). In addition, perceived physical fitness measured by the International Fitness Scale. 3. Physical activity and sedentarism measured using tri-axial accelerometers at baseline, post-intervention and follow-up (4 months post-intervention). Furthermore, these variables are measured using the Youth Activity Profile questionnaire. Additionally, the influence of previous physical activities on bone is measured using the bone-specific physical activity questionnaire. 4. Calcium intake measured using a food-frequency questionnaire at baseline, post-intervention and follow-up (4 months post-intervention). Vitamin D status measured using the vitamin D questionnaire at baseline, post-intervention and follow-up (4 months post-intervention) 5. Biochemical markers measured using venous blood samples between 8:00 and 10:00 after an overnight fast at baseline, post-intervention and follow-up (4 months post-intervention) 6. Psychological distress measured using State-Trait Anxiety Inventory for Children (STAIC-T), Children Depression Inventory (CDI) and Positive Affect Schedule for children (PANAS-C) at baseline, post-intervention and follow-up (4 months post-intervention) 7. Well-being measured using Subjective Happiness Scale (SHS), Life Orientation Test-Revised (LOT-R) and Positive Affect Schedule for children (PANAS-C) at baseline, post-intervention and follow-up (4 months post-intervention) 8. Quality of life measured using the Paediatric Quality of Life Inventory (PedsQLTM 4.0 Generic Core Scales) at baseline, post-intervention and follow-up (4 months post-intervention) Previous secondary outcome measures: 1. Biochemical markers measured using venous blood samples between 8:00 and 10:00 after an overnight fast at baseline, post-intervention and follow-up (4 months post-intervention) 2. Physical activity measured using tri-axial accelerometers at baseline, post-intervention and follow-up (4 months post-intervention) 3. Physical fitness measured using the ALPHA fitness test battery at baseline, post-intervention and follow-up (4 months post-intervention) 4. Psychological distress measured using State-Trait Anxiety Inventory for Children (STAIC-T), Children Depression Inventory (CDI) and Positive Affect Schedule for children (PANAS-C) at baseline, post-intervention and follow-up (4 months post-intervention) 5. Well-being measured using Subjective Happiness Scale (SHS), Life Orientation Test-Revised (LOT-R) and Positive Affect Schedule for children (PANAS-C) at baseline, post-intervention and follow-up (4 months post-intervention) 6. Quality of life measured using the Paediatric Quality of Life Inventory (PedsQLTM 4.0 Generic Core Scales) at baseline, post-intervention and follow-up (4 months post-intervention)
Completion date	25/01/2023

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Years
Upper age limit	18 Years
Sex	All
Target sample size at registration	116
Total final enrolment	116
Key inclusion criteria	1. Paediatric cancer survivors 6 to 18 years old 2. ≥1 year from diagnosis 3. Have been exposed to radiotherapy or chemotherapy 4. Not currently receiving treatment for cancer
Key exclusion criteria	1. Simultaneous participation in another study 2. Previous diagnosed anorexia nervosa/bulimia; known pregnancy, alcohol or drug abuse 3. Children requiring chronic oral glucocorticoid therapy or pharmacologic agents for reduced BMD other than calcium or vitamin D 4. Presence of an injury (before inclusion) that may affect daily life activities and can be aggravated by exercise 5. Have a lower limb prosthesis
Date of first enrolment	01/09/2020
Date of final enrolment	21/03/2022

Locations

Countries of recruitment

Spain

Study participating centres

Virgen de las Nieves Hospital

Ribera del Beiro, s/n
Granada
18014
Spain

Reina Sofía Hospital

Menendez Pidal, s/n
Córdoba
14004
Spain

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan	The datasets generated during and/or analysed during the current study are not expected to be made available due to confidentiality.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	08/10/2020	14/10/2020	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

19/09/2024: The following changes were made to the trial record:
1. The overall trial end date was changed from 01/02/2023 to 25/01/2023.
2. The intention to publish date was changed from 01/06/2024 to 31/05/2025.
3. Total final enrolment added.
20/06/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/09/2020 to 21/03/2022.
2. The overall trial end date was changed from 25/06/2022 to 01/02/2023.
3. The intention to publish date was changed from 31/12/2022 to 01/06/2024.
4. Ministry of Science and Innovation (Spain) was added as a funder.
5. The primary and secondary outcome measures were updated.
6. The total final enrolment number was added.
14/10/2020: Publication reference added.
14/08/2020: Regional University Hospital of Málaga was removed from the trial participating centres.
11/08/2020: The interventions and primary and secondary outcome measures were updated. The recruitment start date was changed from 01/08/2020 to 01/09/2020.
10/07/2020: The following changes were made to the trial record:
1. The public title was changed from "Improving bone health in paediatric cancer survivors" to "Improving bone health in paediatric cancer survivors through exercise".
2. The scientific title was changed from "Effect of an exercise program on bone health in paediatric cancer survivors" to "Effect of an online exercise program on bone health in paediatric cancer survivors".
3. The overall end date was changed from 30/04/2022 to 25/06/2022.
4. The recruitment start date was changed from 01/05/2020 to 01/08/2020.
5. The recruitment end date was changed from 15/06/2020 to 30/09/2020.
6. The plain English summary was updated to reflect these changes.
10/07/2020: The following changes have been made:
1. The target number of participants has been changed from "A minimum of 102 participants (51 per group)" to "A minimum of 116 participants (58 per group)".
2. The intention to publish date has been changed from 31/12/2024 to 31/12/2022.
02/04/2020: Trial’s existence confirmed by Junta de Andalucia