Pain and Sleep Disturbances in Children Living Beyond Cancer: A Case-Control Study

Not yet recruiting

• Conditions: Childhood Cancer Survivors

• Registration Number: NCT07120646
• Lead Sponsor: Vrije Universiteit Brussel

Brief Summary

Children living beyond cancer (CBC) represent a unique and growing population of young people in need of long-term clinical support. Studies suggest that 11-44% of CBC experience chronic pain, negatively impacting a wide range of child biopsychosocial outcomes and creating high financial burden for their families and society. Often comorbid with pain, one of the most chronic and disturbing side effects reported by CBC are sleep disturbances, and in particular, difficulties initiating and maintaining sleep. Indeed, \>50% of CBC report some form of sleep disturbance even 9 to 15 years after the cancer diagnosis. Much attention has been paid to sleep and pain as independent constructs within pediatric oncology, yet Belgian data is lacking. Additionally, little is known about how these domains interact with one another and subsequent indications for prevention and intervention. Although evidence shows an interrelationship between pain and sleep in adult and pediatric populations, this interrelationship is understudied in childhood cancer patients and CBC. (Chronic) pain may serve as a modifiable target for interventions to improve sleep quality and vice versa, and understanding this relationship is crucial for providing comprehensive care to CBC. Therefore, this cross-sectional case-control study aims to explore the differences in pain and sleep disturbances in CBC compared to healthy age- and sex-matched healthy controls, as well as the interrelationship between both outcomes.

Detailed Description

Pain and sleep disturbances are common and impactful following childhood cancer treatment

Worldwide, about 400 000 children aged 0-19 years are diagnosed with cancer each year. Largely due to more intensive treatment regimens and the implementation of immunotherapy for high-risk patients, 5-year survival rates for children with cancer in high income countries have increased to \>80%. This is great news, however as a result, children living beyond cancer (CBC) represent a unique and growing population of young people in need of long-term clinical support.

Across the cancer continuum, pain is a prevalent, recurrent, and impactful symptom. Although we know that pain in childhood cancer is underreported and undertreated, the prevalence of pain in children during active cancer treatment varies from 28-62% across studies, with \>50% of children reporting moderate to severe pain intensity. For many children, pain resolves following completion of the cancer treatment, yet for some, pain persists well beyond treatment7 and into adulthood. Indeed, studies suggest that 11-44% of CBC experience chronic pain (i.e., pain in ≥ 1 anatomic region persisting or recurring for \>3 months), with 20% reporting moderate to extreme pain interference. Chronic pain can deleteriously impact the lives of CBC and their family. Specifically, if not addressed early on, chronic pain can negatively impact children's school functioning, sleep quality, social and family functioning, mental health, physical activity, and overall health-related quality of life. Moreover, it increases the risk of chronic pain across the lifespan. Further, also the families of children with chronic pain can experience significant physical and psychosocial sequelae due to the child's pain, e.g., high levels of anxiety and depressive symptoms, and a high financial burden due to direct and indirect medical costs.

Often comorbid with pain, one of the most chronic and disturbing side effects reported by childhood cancer patients and CBC are sleep disturbances, and in particular, difficulties initiating and maintaining sleep, suggesting that this is a major quality of life concern. Indeed, \>50% of CBC report some form of sleep disturbance even 9 to 15 years after the cancer diagnosis. Good-quality sleep in childhood is crucial for a healthy emotional, cognitive, physical, and behavioral development. Healthy sleep involves receiving a developmentally appropriate number of hours of sleep (declining from infancy to adolescence), few or preferably no wakings during the night, and a subjective perception of feeling rested. CBC may be at increased risk for sleep disturbances, being critically ill during a life phase that is important in the development of good sleep habits. Disrupted sleep can also affect inflammatory pathways and immune functioning, incl. natural killer cell activity, and can contribute to or exacerbate other morbidities common to survivorship (e.g., anxiety, depression). Sleep disruption is unlikely to remit without intervention and longitudinal research shows that sleep disruption often persists from childhood into adolescence.

Study Rationale and Purpose

Some attention has been paid to sleep and pain as independent constructs within pediatric oncology, although Belgian data is lacking and little is known about how these domains interact with one another and subsequent indications for prevention and intervention. Early studies propose a bi-directional relationship between pain and sleep, such that sleep deficiency and pain reciprocally maintain symptoms over time. Yet, the interrelationship between pain and sleep is understudied in childhood cancer patients and CBC. (Chronic) pain may serve as a modifiable target for interventions to improve sleep quality and vice versa, and understanding this relationship is crucial for providing comprehensive care to CBC.

This cross-sectional case-control study aims to explore the differences in pain and sleep disturbances in CBC (6-12 years old) compared to healthy age- and sex-matched healthy controls, as well as the interrelationship between both outcomes.

Study Timeline

• Study First Submitted: 2025-06-26
• Status Verified: 2025-08
• Study Start: 2025-08-01
• Study First Submitted QC: 2025-08-11
• Last Update Submitted: 2025-08-11
• Study First Posted: 2025-08-13
• Last Update Posted: 2025-08-13
• Primary Completion: 2026-06
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 76

Inclusion Criteria

• CBC: 1) current age 6-12yo; 2) history of any cancer diagnosis; 3) ≤ 5y post- treatment completion; 4) ≥ 3 months since last cancer treatment (since pain and insomnia during treatment can be directly related to therapy and recover spontaneously); 5) fluent Dutch speaker and reader (age-dependent)
• Healthy controls (age- and sex-matched): 1) current age 6-12yo; 2) no history of cancer ; 3) fluent Dutch speaker and reader (age-dependent)
• Parents: 1) fluent Dutch speaker and reader

Exclusion Criteria

• CBC: 1) receiving palliative therapy; 2) psychiatric disorder; 3) severe intellectual disability
• Healthy controls: 1) history of cancer; 2) psychiatric disorder; 3) severe intellectual disability

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Activity limitations due to pain	Baseline about the past 14 days + 14 days following baseline in daily sleep diary	Measured with the Child Activity Limitations Interview (CALI) - 9 (parent-report version for the 6-7 year-olds; self-report version for the 8-12 year-olds)
Sleep disturbances	Baseline	Assessed with the PROMIS Parent Proxy Item Bank v1.0 - Sleep Disturbance - Short Form 8a parent-report for the 6-7 year olds and PROMIS Pediatric Item Bank v1.0 - Sleep Disturbance - Short Form 8a for the 8-12 year-olds. Additionally, this outcome measure is assessed with the Children's Sleep Habits Questionnaire (CSHQ) (parent-report for all ages).

Secondary Outcome Measures

Name	Time	Method
Pain severity	Baseline	Assessed with the Pain Frequency Severity Duration scale (PFSD) (parent-report for the 6-7 year-olds; self-report for the 8-12 year-olds)
Pain coping	Baseline	Assessed with the Pain Coping Questionnaire short form (parent-report for the 6-7 year-olds; self-report for the 8-12 year-olds)
Pain reporting and assessment during follow-up care	Baseline	Assessed using a selfmade set of items about pain reporting and assessment during medical follow-up consultations
Health-related quality of life	Baseline	Assessed with the PedsQL Generic Score Scales 4.0 (5-7yo parent-report) for the 6-7 year-olds and the PedsQL Generic Score Scales 4.0 (8-12yo self-report) for the 8-12 year-olds.
Fatigue	Baseline	Assessed with the PedsQL Multidimensional Fatigue Scale 3.0 (5-7yo parent-report) for the 6-7 year-olds and the PedsQL Multidimensional Fatigue Scale 3.0 (8-12yo self-report) for the 8-12 year-olds.
Anxiety	Baseline	Assessed with the PROMIS Parent Proxy 3.0 - Anxiety - Short Form 8a for 6-7 year-olds and the PROMIS Pediatric 3.0 - Anxiety - Short Form 8a for the 8-12 year-olds.
Depressive symptoms	Baseline	Assessed with the PROMIS Parent Proxy 3.0 - Depressive Symptoms - Short Form 6a for the 6-7 year-olds and the PROMIS Pediatric 3.0 - Depressive Symptoms - Short Form 6a for the 8-12 year-olds.
Total sleep time	14 days following baseline	The total amount of time scored as sleep in minutes from sleep onset to sleep offset. Assessed with Actigraphy (Fitbit Sense 2)
Wake minutes after sleep onset	14 days following baseline	The number of minutes scored as wake after nighttime sleep onset. Assessed with Actigraphy (Fitbit Sense 2)
Sleep efficiency	14 days following baseline	The ratio of total sleep time and total time spent in bed at night as a percentage, with values closer to 100 indicating more efficient sleep. Assessed with Actigraphy (Fitbit Sense 2)
Sleep regularity index	14 days following baseline	Similarity of the child's sleep-wake pattern from one day to the next based on binary sleep-wake time series. Assessed with Actigraphy (Fitbit Sense 2)
Pain symptoms during the day	14 days following baseline	This data is collected via a daily sleep diary and includes: presence of pain (yes/no), and if yes; mean and worst pain during the day (0 = no pain; 10 = worst pain possible)
Medication intake during the day	14 days following baseline	This data is collected via a daily sleep diary and includes whether the child took medication during the day (yes/no), and if yes; which medication.

Trial Locations

Locations (1)

Vrije Universiteit Brussel; 🇧🇪 Jette, Brussels-Capital Region, Belgium