Lung CancerNCT04070651
Sleep and Immune Checkpoint Inhibitors
An observational study of Lung Cancer, run by Aarhus University Hospital at 1 site in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- How many people
- 49 participants
- Where
- 1 siteDenmark
- Study dates
- 5 Aug 2019to 1 Jul 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Men and women diagnosed with advanced non-small cell lung cancer, treated with immune checkpoint inhibitors, at Aarhus University Hospital, Denmark.
Who may be able to join
- Confirmed diagnosis of advanced non-small cell lung cancer
Who cannot join
- Insufficient Danish proficiency
- Pre-existing confounding psychiatric illnesses
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sleep Disturbance and Its Association With Fatigue, Depressive Symptoms, and Clinical Response to Immune Checkpoint Inhibitors (ICI) in Lung Cancer Patients
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.
Read the detailed description
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.
- Conditions
- Lung Cancer
- Keywords
- Sleep, Fatigue, Depressive symptoms, Immune Checkpoint Inhibitors, Lung Cancer, Clinical response
- Medical subject headings
- Lung Neoplasms, Fatigue, Depression
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical response to treatment
Radiological evaluation of the clinical response to treatment with ICI, according to RECIST criteria.
Measured: Changes from baseline to 9 and 18 weeks after treatment initiation, respectively.
Secondary outcomes (21)
Insomnia Severity
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).
Measured: Weekly from baseline to 18 weeks after treatment initiation, and follow-up 1, 2 and 3 years from baseline, respectively.
Sleep diary
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).
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Fatigue
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.
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Depressive symptoms
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.
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Health-related quality of life
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.
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Disease specific health-related quality of life
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.
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Perceived Stress
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.
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Sickness behavior
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.
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Cortisol
Cortisol awakening response (CAR), and the diurnal cortisol slope (DCS)
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 1
CRP
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 2
IL-6
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 3
TNF-a
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 4
Se-Cortisol
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 5
White blood cell count.
Measured: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Actigraphy 1
Objective sleep outcome. Nightly sleep onset latency (SOL)
Measured: Baseline to 18 weeks after initiation of treatment.
Actigraphy 2
Objective sleep outcome: Wakefulness after initial sleep onset (WASO)
Measured: Baseline to 18 weeks after initiation of treatment.
Actigraphy 3
Objective sleep outcome: Total sleep time (TST)
Measured: Baseline to 18 weeks after initiation of treatment.
Actigraphy 4
Objective sleep outcome: Total time spent in bed (TIB)
Measured: Baseline to 18 weeks after initiation of treatment.
Actigraphy 5
Objective sleep outcome: Sleep efficiency (SE, i.e., the percent of the time asleep out of amount of time spent in bed)
Measured: Baseline to 18 weeks after initiation of treatment.
Actigraphy 6
Objective sleep outcome: Circadian activity rhythms.
Measured: Baseline to 18 weeks after initiation of treatment.
Disease status
Changes in disease status after treatment initiation with ICI. Changes are evaluated according to RECIST criteria.
Measured: 1, 2 and 3 years from treatment initiation (baseline).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start5 Aug 2019
- Primary completion1 Jun 2023
- Study completion1 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Aarhus
- Responsible party
- Principal investigator, Louise Strøm, University of Aarhus
- Investigators
- Robert Zachariae, Prof., DMSc, Study director, Aarhus University and Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04070651
- Sponsor's protocol ID
- Sleep.ICI
- Status last verified
- Aug 2024
- First submitted
- 23 Aug 2019
- Last updated
- 6 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Strom L, Zachariae R, Wu LM, Meldgaard P, Ancoli-Israel S, Lekander M, Mroczek D, Amidi A. Longitudinal investigation of sleep and circadian rest-activity rhythms in non-small cell lung cancer patients during immunotherapy and associations with fatigue, depression, and perceived stress. Sleep Med. 2025 Oct;134:106740. doi: 10.1016/j.sleep.2025.106740. Epub 2025 Aug 10.
PubMed 40815894
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sleep Disturbance and Its Association With Fatigue, Depressive Symptoms, and Clinical Response to Immune Checkpoint Inhibitors (ICI) in Lung Cancer Patients
- ClinicalTrials.gov ID
- NCT04070651
- Acronym / sponsor ID
- Sleep.ICI
- Conditions
- Lung Cancer
- Keywords
- Sleep, Fatigue, Depressive symptoms, Immune Checkpoint Inhibitors, Lung Cancer, Clinical response
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Collaborators
- University of Aarhus
- Study start
- 5 Aug 2019 (actual)
- Primary completion
- 1 Jun 2023 (actual)
- Study completion
- 1 Jul 2023 (actual)
- First posted
- 28 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Men and women diagnosed with advanced non-small cell lung cancer, treated with immune checkpoint inhibitors, at Aarhus University Hospital, Denmark.
Key inclusion criteria (1 listed)
- Confirmed diagnosis of advanced non-small cell lung cancer
Key exclusion criteria (2 listed)
- Insufficient Danish proficiency
- Pre-existing confounding psychiatric illnesses
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
21 secondary outcomes
Insomnia Severity
Time frame: Weekly from baseline to 18 weeks after treatment initiation, and follow-up 1, 2 and 3 years from baseline, respectively.
Sleep diary
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
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.
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.
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.
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.
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.
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.
Cortisol
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 1
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 2
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 3
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 4
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 5
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Actigraphy 1
Time frame: Baseline to 18 weeks after initiation of treatment.
Actigraphy 2
Time frame: Baseline to 18 weeks after initiation of treatment.
Actigraphy 3
Time frame: Baseline to 18 weeks after initiation of treatment.
Actigraphy 4
Time frame: Baseline to 18 weeks after initiation of treatment.
Actigraphy 5
Time frame: Baseline to 18 weeks after initiation of treatment.
Actigraphy 6
Time frame: Baseline to 18 weeks after initiation of treatment.
Disease status
Time frame: 1, 2 and 3 years from treatment initiation (baseline).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
- Derived from this study: PubMed 40815894Strom L, Zachariae R, Wu LM, Meldgaard P, Ancoli-Israel S, Lekander M, Mroczek D, Amidi A. Longitudinal investigation of sleep and circadian rest-activity rhythms in non-small cell lung cancer patients during immunotherapy and associations with fatigue, depression, and perceived stress. Sleep Med. 2025 Oct;134:106740. doi: 10.1016/j.sleep.2025.106740. Epub 2025 Aug 10.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Zachariae, Prof., DMSc study director
Aarhus University and Aarhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Cancer, run by Aarhus University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical response to treatment (time frame: Changes from baseline to 9 and 18 weeks after treatment initiation, respectively.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04070651, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024.