Chrono-behavioral Therapy for Chronic Fatigue in Cancer (ChronoBT)

Cancer-related fatigue (CRF) is a severe and persistent side effect of cancer and its treatment, affecting up to 40% of patients and significantly reducing quality of life. Recent research suggests that circadian rhythm disruption has been implicated as a possible related pathophysiological mechanism underlying CRF. Circadian rhythms are 24-hour cycles regulating physiology and behavior through environmental cues called "zeitgebers." Strengthening these cues-such as light exposure, physical activity, and eating-may help reduce CRF.

This project will develop and test the optimal combination a home-based, low-burden chrono-behavioral therapy (ChronoBT) targeting these zeitgebers.

Study Overview

• Status: Not yet recruiting
• Conditions: Cancer Survivors; Chronic Fatigue
• Intervention / Treatment: Behavioral: Chronotherapy; Behavioral: Control

Detailed Description

Cancer-related fatigue (CRF) is frequently reported as the most severe and distressing side effect of cancer and its treatment. Among cancer patients, up to 40% will experience CRF that can last months or even years after treatment and it is also deleterious to quality of life. However, there is still no established CRF treatment. Underlying mechanisms of CRF are likely multi-factorial and recently, circadian rhythm disruption has been implicated as a possible related pathophysiological mechanism underlying CRF. Circadian rhythms are endogenous 24-hour cycles of rhythmicity in physiology and behavior orchestrated by the suprachiasmatic nuclei (SCN) in the brain. They are entrained to the environment via time-giving cues called "zeitgebers". Thus, improving circadian rhythm robustness by strengthening modifiable zeitgebers is one potential way to ameliorate CRF. The overarching goal of the proposed project is to conduct an optimization trial of a home-based, low-burden multicomponent chrono-behavioral therapy (ChronoBT) that aims to strengthen the effects of 3 zeitgebers to treat CRF - light/dark exposure, physical activity and eating - all of which individually have shown promise in strengthening circadian rhythms and reducing fatigue. The study will include two work packages: In Work Package 1 (WP1), the investigators will pilot test candidate intervention components in prostate and female breast cancer survivors. In Work Package 2 (WP2), a fully powered optimization trial will be undertaken using the framework - the Multiphase Optimization Strategy (MOST), to test the optimal combination of ChronoBT components.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lisa M Wu, PhD; Phone Number: +45 87153748; Email: lisa.wu@psy.au.dk
• Study Contact Backup: Name: Louise Strøm, PhD; Phone Number: +45 87165076; Email: louisestroem@oncology.au.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University and Aarhus University Hospital
    • Contact: Lisa M Wu, PhD; Phone Number: +45 87153748; Email: lisa.wu@psy.au.dk
    • Contact: Louise Strøm, PhD; Phone Number: +45 87165076; Email: louisestroem@oncology.au.dk
    • Contact: Lisa M Wu, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. prostate or female breast cancer survivors
2. completed local and/or adjuvant cancer therapy (with the exception of hormonal therapy) ≥ 1 year previously
3. ≥18 years of age
4. able to speak and read Danish
5. experiencing CRF (score ≤36 on FACT-F)

Exclusion Criteria:

1. use of light therapy in the last year
2. confounding underlying medical/psychiatric disorders or use of medications associated with fatigue (e.g., a central nervous system cancer, untreated hypothyroidism, anemia, chronic fatigue syndrome, insomnia, major depression)
3. non-cancer related factor likely to be a driver of fatigue (e.g., shift work, pregnancy, recent travel across time zones)
4. recurrence of cancer or new cancer
5. physical or psychological conditions that could prevent participation in intervention components
6. use of photosensitizing medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Condition A: light/dark, eating and activity; Condition A: light/dark, eating and activity: Bright white light glasses 30 minutes upon awakening and blue light blocking glasses 3 hours before bedtime; eating within a 10-hour window, and taking a 15 minutes daily walk.	Behavioral: Chronotherapy; This study utilize and test different combinations of three types of interventions (zeitgebers) to entrain the circadian rhythm: 1) Light being the primary photic zeitgebers that directly entrain the SCN, 2) physical activity and 3) timing of eating) being non-photic zeitgebers that drive peripheral rhythms.
Experimental: Condition B: Light/dark and eating; Condition B: Light/dark and eating: Bright white light glasses 30 minutes upon awakening and blue light blocking glasses 3 hours before bedtime and eating within a 10-hour window.	Behavioral: Chronotherapy; This study utilize and test different combinations of three types of interventions (zeitgebers) to entrain the circadian rhythm: 1) Light being the primary photic zeitgebers that directly entrain the SCN, 2) physical activity and 3) timing of eating) being non-photic zeitgebers that drive peripheral rhythms.
Experimental: Condition C: Light/dark and activity; Condition C: Light/dark and activity: Bright white light glasses 30 minutes upon awakening and blue light blocking glasses 3 hours before bedtime and taking a 15 minutes daily walk.	Behavioral: Chronotherapy; This study utilize and test different combinations of three types of interventions (zeitgebers) to entrain the circadian rhythm: 1) Light being the primary photic zeitgebers that directly entrain the SCN, 2) physical activity and 3) timing of eating) being non-photic zeitgebers that drive peripheral rhythms.
Experimental: Condition D: Eating and activity; Condition D: Eating and activity: Eating within a 10-hour window and taking a 15 minutes daily walk.	Behavioral: Chronotherapy; This study utilize and test different combinations of three types of interventions (zeitgebers) to entrain the circadian rhythm: 1) Light being the primary photic zeitgebers that directly entrain the SCN, 2) physical activity and 3) timing of eating) being non-photic zeitgebers that drive peripheral rhythms.
Experimental: Condition E: Light/dark; Condition E: Light/dark: Bright white light glasses 30 minutes upon awakening and blue light blocking glasses 3 hours before bedtime	Behavioral: Chronotherapy; This study utilize and test different combinations of three types of interventions (zeitgebers) to entrain the circadian rhythm: 1) Light being the primary photic zeitgebers that directly entrain the SCN, 2) physical activity and 3) timing of eating) being non-photic zeitgebers that drive peripheral rhythms.
Experimental: Condition F: Eating; Condition F: Eating: Eating within a 10-hour window	Behavioral: Chronotherapy; This study utilize and test different combinations of three types of interventions (zeitgebers) to entrain the circadian rhythm: 1) Light being the primary photic zeitgebers that directly entrain the SCN, 2) physical activity and 3) timing of eating) being non-photic zeitgebers that drive peripheral rhythms.
Experimental: Condition G: Activity; Condition G: Activity: Taking a15 minutes daily walk.	Behavioral: Chronotherapy; This study utilize and test different combinations of three types of interventions (zeitgebers) to entrain the circadian rhythm: 1) Light being the primary photic zeitgebers that directly entrain the SCN, 2) physical activity and 3) timing of eating) being non-photic zeitgebers that drive peripheral rhythms.
Active Comparator: Condition H: Circadian watch; Condition H: Circadian watch: Waring a circadian watch to access circadian activity	Behavioral: Control; Control condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer-related Fatigue	Cancer-related Fatigue by the Functional Assessment of Cancer Therapy - Fatigue Scale (FACT-F) Number of items: 13. Score range: 0-52. Lower score indicates more fatigue.	T1 (Baseline, pre-intervention), T2 (two weeks post intervention initiation), T3 (1 day post intervention completion), T4 (follow-up 4 weeks post intervention completion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Quality	Sleep quality by the Pittsburg Sleep Quality Index (PSQI), measuring seven domains. Higher score indicates worse sleep.	T1 (Baseline, pre-intervention), T2 (two weeks post intervention initiation), T3 (1 day post intervention completion), T4 (follow-up 4 weeks post intervention completion)
Insomnia	Insomnia by the Insomnia Severity Index (ISI). Number of items: 7. Score range: 0-28. Higher score indicate worse insomnia.	T1 (Baseline, pre-intervention), T2 (two weeks post intervention initiation), T3 (1 day post intervention completion), T4 (follow-up 4 weeks post intervention completion)
Anxiety and Depression	Anxiety and Depression by the Hospital Anxiety and Depression Scale (HADS). Number of items: 14. Score range: 0-21 for each domain. Higher score indicates worse symptoms.	T1 (Baseline, pre-intervention), T2 (two weeks post intervention initiation), T3 (1 day post intervention completion), T4 (follow-up 4 weeks post intervention completion)
Health-related Quality of Life	Health-related Quality of Life by the Functional Assessment of Cancer Therapy - General (FACT-G). Number of items: 27. Score range: 0-128. Higher score indicates worse quality of life.	T1 (Baseline, pre-intervention), T2 (two weeks post intervention initiation), T3 (1 day post intervention completion), T4 (follow-up 4 weeks post intervention completion)
Cognition	Quality of Life - Cognition items from the European Organization for Research and Treatment of Cancer Questionnaires (EORTC-QLQ-30). Number of items: 2. Score range: 2-8. Higher score indicate more impairment.	T1 (Baseline, pre-intervention), T2 (two weeks post intervention initiation), T3 (1 day post intervention completion), T4 (follow-up 4 weeks post intervention completion)
Circadian Function	Circadian Function Index derived from actigraphy data. Score range: 0-1. Higher score indicate more robust rhythms.	During the entire period of intervention and follow-up T4 (4 weeks post intervention completion)
Chronotype	Chronotype by the reduced Morningness-Eveningness Questionnaire (rMEQ). Number of items: 5. Score range 5-25. Higher score indicates closer to morningness type, while lower score indicate closer to eveningness type.	T1 (Baseline)
Credibility/Expectancy	Credibility/Expectancy by the Credibility/Expectancy Questionnaire (CEQ). Number of items: 6. Item score range: 1-9. Higher score indicates more credibility/expectancy.	T1 (Baseline)
Treatment Satisfaction	Treatment Satisfaction by the Functional Assessment of Chronic Illness Therapy - Treatment Satisfaction - General (FACIT-TS-G). Number of items: 8. Score range: 0-21. Higher score indicates better satisfaction.	T3 (1 day post intervention completion), T4 (follow-up 4 weeks post intervention completion)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence and fidelity	Start/end times of component(s) and protocol deviations by personal logs	During the intervention period: One week for WP1, and four weeks for WP2

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: University of Aarhus
• Investigators: Principal Investigator: Lisa M Wu, PhD, University of Aarhus; Principal Investigator: Ali Amidi, PhD, University of Aarhus

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: February 17, 2025
• First Submitted That Met QC Criteria: February 24, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 13, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Fatigue
• Other Study ID Numbers: ChronoBT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No