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Completed

NCT Number: NCT04070651

Sleep and Immune Checkpoint Inhibitors

Sleep disturbances are prevalent in cancer patients and linked to levels of fatigue and depressive symptoms with a major impact on quality of life. A growing body of evidence links sleep disturbances with various health outcomes, including increased risk of depression, cancer, and overall mortality. Inflammation is suggested to be an underlying mechanism both driving and maintaining the symptom cluster of sleep disturbance, fatigue and depressive symptoms, as well as being bi-directionally linked to sleep. The main purpose of the present study is to investigate the prevalence of sleep disturbance and its association with psychological and physical symptoms as well as the clinical response to ICI in non-small-cell lung cancer patients (NSCLC), with a secondary aim of exploring the role of inflammation.

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Key information

Conditions

Lung Cancer Behavior Behavioral Symptoms Depression Fatigue Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Respiratory Tract Neoplasms Signs and Symptoms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Aarhus University Hospital

Aarhus, Central Jutland, 8200, Denmark

About this study

A total of 240 cancer patients diagnosed with advanced NSCLC, referred to treatment with ICI will be enrolled in this prospective observational study. Patients will be assessed prior to initiation of treatment (baseline) and every third subsequent week, corresponding to each treatment cycle over a period of 18 weeks. Assessments will include questionnaires, sleep diaries, actigraphy, and blood and saliva samples to examine sleep, fatigue, psychological and physical symptoms, the sleep-wake-cycle, inflammation, and cortisol. Additionally, the patients will be asked to complete a reduced questionnaire every week within the 18 weeks period, to address weekly fluctuations in sleep quality, fatigue, and mood. Treatment response is assessed after 9 and 18 weeks.

Aims:

  • To explore possible associations between sleep and the clinical response to treatment with ICI.
  • To investigate the prevalence of sleep disturbance in patients with NSCLC during treatment with ICI.
  • To prospectively assess changes in sleep parameters over the course of treatment.
  • To examine associations between sleep parameters and fatigue, depression, anxiety, and inflammation.
  • To explore possible associations between sleep, fatigue, depression, inflammatory responses and the clinical response to treatment with ICIs.

Hypotheses:

Patients with high levels of sleep disturbance (insomnia severity) will experience 1) poorer clinical response to ICI, 2) more depressive symptoms, 3) higher levels of fatigue, 4) poorer overall health-related quality of life (HRQoL), 5) higher levels of inflammation.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Confirmed diagnosis of advanced non-small cell lung cancer

Exclusion criteria

  • Insufficient Danish proficiency
  • Pre-existing confounding psychiatric illnesses

Treatment and study plan

Primary outcomes

  1. Clinical response to treatment

    Time frame: Changes from baseline to 9 and 18 weeks after treatment initiation, respectively.

    Radiological evaluation of the clinical response to treatment with ICI, according to RECIST criteria.

Secondary outcomes

  1. Insomnia Severity

    Time frame: Weekly from baseline to 18 weeks after treatment initiation, and follow-up 1, 2 and 3 years from baseline, respectively.

    Changes in insomnia severity as measured with The Insomnia Severity Index (ISI). Total score ranges from 0 to 28. Interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).

  2. Sleep diary

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.

    Changes in Standard sleep metrics (nightly sleep onset latency (SOL), wakefulness after initial sleep onset (WASO), total sleep time (TST), total time spent in bed (TIB), sleep efficiency (SE).

  3. Fatigue

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.

    Changes in subjective fatigue as measured with the Multidimensional Fatigue Symptom Inventory - Short Form (MFSI-SF). Subscales (general, physical, emotional, and mental fatigue) are summed and the vigor scale subtracted to create a fatigue total score, with higher scores indicating higher levels of fatigue.

  4. Depressive symptoms

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.

    Changes in depressive symptoms as measured with the Patient-Reported Outcomes Measurement Information System (PROMIS®) Depression - Short Form 8a. Total raw score ranges from 8 to 40, with higher scores indicating greater severity of depression.

  5. Health-related quality of life

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.

    Changes in health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life questionnaire for cancer patients (EORTC QLQ-C30). The standardized raw score, ranges from 0 to 100; a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.

  6. Disease specific health-related quality of life

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.

    Changes in disease specific health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life Lung Cancer Module (EORTC QLQ-LC29). The standardized raw score, ranges from 0 to 100; a high score for the symptom scales / single items represents a high level of symptomatology or problems.

  7. Perceived Stress

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.

    Changes in perceived stress as measured with The Perceived Stress Scale (PSS). Total score ranges from 0 to 40, with higher scores indicating higher perceived stress.

  8. Sickness behavior

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.

    Changes in subjective sickness behavior as measured with the Sickness Questionnaire (SicknessQ). Total score ranges from 0 to 30, with higher scores indicating more sickness behaviour.

  9. Cortisol

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.

    Cortisol awakening response (CAR), and the diurnal cortisol slope (DCS)

  10. Inflammatory response 1

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.

    CRP

  11. Inflammatory response 2

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.

    IL-6

  12. Inflammatory response 3

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.

    TNF-a

  13. Inflammatory response 4

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.

    Se-Cortisol

  14. Inflammatory response 5

    Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.

    White blood cell count.

  15. Actigraphy 1

    Time frame: Baseline to 18 weeks after initiation of treatment.

    Objective sleep outcome. Nightly sleep onset latency (SOL)

  16. Actigraphy 2

    Time frame: Baseline to 18 weeks after initiation of treatment.

    Objective sleep outcome: Wakefulness after initial sleep onset (WASO)

  17. Actigraphy 3

    Time frame: Baseline to 18 weeks after initiation of treatment.

    Objective sleep outcome: Total sleep time (TST)

  18. Actigraphy 4

    Time frame: Baseline to 18 weeks after initiation of treatment.

    Objective sleep outcome: Total time spent in bed (TIB)

  19. Actigraphy 5

    Time frame: Baseline to 18 weeks after initiation of treatment.

    Objective sleep outcome: Sleep efficiency (SE, i.e., the percent of the time asleep out of amount of time spent in bed)

  20. Actigraphy 6

    Time frame: Baseline to 18 weeks after initiation of treatment.

    Objective sleep outcome: Circadian activity rhythms.

  21. Disease status

    Time frame: 1, 2 and 3 years from treatment initiation (baseline).

    Changes in disease status after treatment initiation with ICI. Changes are evaluated according to RECIST criteria.

Sponsors and collaborators

Lead sponsor

Aarhus University Hospital

Other

Collaborators

  • University of Aarhus

Registry information

Official study title

Sleep Disturbance and Its Association With Fatigue, Depressive Symptoms, and Clinical Response to Immune Checkpoint Inhibitors (ICI) in Lung Cancer Patients

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Aug 28, 2019
Registry last updated
Aug 6, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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