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NCT Number: NCT07460999

Singing Training vs Usual Care 6-18 Months After Surgical Resection for Non-small Cell Lung Cancer (NSCLC)

People who have undergone curative surgery for non-small cell lung cancer (NSCLC) often experience reduced quality of life (QoL), a high burden of symptoms, and physical deconditioning. Current Danish rehabilitation offers are heterogeneous and inconsistent and not tailored to the specific needs of this population. Additionally, some patients continue to suffer from persistent physical symptoms months or even years after surgery, yet no targeted support is currently available for them. Singing - delivered as a structured form of training - has shown benefits in improving both physical and psychological outcomes in individuals with chronic obstructive pulmonary disease (COPD). Although singing has not yet been studied in NSCLC patients, the two conditions share overlapping symptoms and characteristics. Therefore, the present study aims to explore whether a singing-based intervention can help reduce symptom burden and improve physical function and QoL in NSCLC patients 6 to 18 months post-surgery. To test this, a multi-centre randomised controlled trial (RCT) will be conducted, comparing a singing intervention to usual care. Given that travel and distance often pose significant barriers to participation, the intervention will be delivered online.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

August Krogh Section for Molecular and Human Physiology, Department of Nutrition, Exercise, and Sports, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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About this study

Post-surgical rehabilitation should include combined aerobic training and strength training, alone or combined with respiratory muscle training. A Cochrane review (Cavalheri, et al., 2019) concluded that rehabilitation with exercise training improved physical capacity and physical fitness and suggested improved Health-Related QoL and dyspnoea. Additionally, a Core Outcomes Set (Edbrooke, et al., 2025) defined critical outcomes as: physical function, HRQoL, breathlessness, activities of daily living, emotional and mental well-being, pain.

In a recent Danish mapping study (Kaasgaard, et al., 2024), a large proportion experiences physiological-oriented symptoms: Fatigue (78%), hyper-vigilance (74%), dyspnoea (65%), and pain (47%); besides psychological-oriented symptoms: Worry about the future (40%), depression (35%), and anxiety (29%). In addition, 27%, experienced having vocal problems. This was confirmed in a subsequent Danish cross-sectional study, which specifically found impaired QoL (physical functioning) and symptoms (dyspnoea) 6-12 months after NSCLC surgery. This aligns with other recent Danish studies demonstrating persistent symptoms long-term after NSCLC surgery. In addition, a systematic review found poor mental health-related QoL, dyspnoea, and pain up to one year after surgery. Taken together, this implies signs of a neglected population with persistent symptoms, yet without a standard offer available to support them.

Singing has become increasingly popular in respiratory diseases, comprising elements of both physiological training and psychosocial aspects, therefore, likely to address the unmet needs in lung cancer. Previous studies have suggested physiological training effects and increased respiratory control, less dyspnoea, improved QoL, and reduced anxiety and depression. Moreover, singing is suggested to confer physiological training effects with work load equivalent to brisk walk pace. Furthermore, singing is perceived as a relevant and beneficial activity that builds joy, meaning, and social cohesion. However, studies have overall mostly been small and heterogenous, and with contradictory findings and a lack of knowledge about the underpinning mechanisms. Moreover, there are different approaches to singing, although a conventional choir approach is mainly adapted. The currently most well-documented, best-practice disease-specific approach is Singing for Lung Health (SLH), developed within a multidisciplinary healthcare setting in the UK since 2008. SLH aims to provide health-promoting benefits, uses exercises and songs as tools for purpose, and, further, includes movement and dancing while singing. In a recent multicentre-RCT in COPD - Sing-a-Lung 1.0 -, the study investigators demonstrated that PR with SLH improved functional capacity and QoL in a dose-response manner and was non-inferior to PR with usual care delivery of physical exercise. Furthermore, SLH was related to improved respiratory strength and dyspnoea control. This RCT was conducted within a real-life community-based setting, was the largest study so far, had sufficient power to detect change (n=270), and, thus, represents a proof-of-concept study.

Singing has not yet been investigated in lung cancer, but a qualitative study exploring singing for patients with breast or colorectal cancer suggests that singing may improve resilience, confidence, and mood, and builds social support. However, given that several epidemiological and common pathogenetic factors are shared between chronic obstructive pulmonary disease (COPD) and NSCLC patients, results from Sing-a-Lung 1.0 are likely to be transferrable specifically to people with lung cancer, and may address important needs of this overlooked group. However, the limited number of lung cancer patients in each municipality and the heterogeneity of current rehabilitation compromise the feasibility of an RCT equally to the one of Sing-a-Lung 1.0. Therefore, as it is expected that the patients will benefit from a singing intervention, singing will be compared with usual care. The singing intervention will be delivered online across all study sites, using video conferencing application, and delivered by three specialised singing teachers. Specifically, the study aims to investigate whether 10 weeks' online singing training (delivered as SLH) improves key physiological and psychosocial outcomes, and reduces symptom burden compared to usual care 6-18 months after curative intended NSCLC surgery, hypothesising that 1) SLH provides relevant and beneficial improvements in both physiological and psychological parameters (superior to usual care alone), and 2) SLH relieves symptom burden (superior to usual care alone). In an exploratory study of a sub-cohort, the study aims to investigate the underpinning mechanisms of singing compared to usual care, hypothesising that 3) SLH improves physical fitness, oxygenation, and inflammation. The overall project will run between Q3 2025 and Q4 2028. Intervention phase: Q1 2026 to Q3 2027. Recruitment and data collection at the following sites: Site 1) Dept. of Medicine, Zealand University Hospital, Roskilde and Næstved, Næstved Hospital, Ringstedgade 61, DK-4700 Naestved, Denmark; Site 2) Dept. of Respiratory Medicine, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400, København NV, Denmark; Site 3) Dept. of Respiratory Medicine, Lillebaelt Hospital, Vejle, Kabbeltoft 25, DK-7100 Vejle, Denmark; Site 4) Dept. of Respiratory Medicine, Odense University Hospital, J. B. Winsløws Vej 4, DK-5000 Odense, Denmark. Specifically, recruitment at Site 2 (or from Site 1 if living close to Copenhagen): Data collection (both for the main study and exploratory sub-study) at site 5) August Krogh Sect. for Molecular and Human Physiology, Dept. of Nutrition, Exercise University of Copenhagen, and Sports, Faculty of Health and Medical Sciences, Universitetsparken 3, DK-2100 København Ø, Denmark. Participants will be recruited using the following methods: 1) Retrospectively: Participants from the recent cross-sectional study, conducted at Site 1 and 2 (Kaasgaard, et al., in peer-review) who indicated to be interested in being part of the study; 2) Retrospectively: Patient lists from the Danish Lung Cancer Registry (DLCR); 3) Prospectively: Ongoing identification in follow-up consultation. Included study participants will be block randomised to either: Group 1: 10 weeks' online SLH, or Group 2: 10 weeks' usual care (followed by an offer of 10 weeks' online SLH). Study participants will be assessed at the following time points: Group 1: 1) T0: Baseline (at randomisation); 2) T1: Follow-up 11-14 weeks later). Group 2: 1) T0: Baseline (at randomisation); 2) T1: Follow-up 11-14 weeks later); 3) T2: Follow-up: Withing three weeks after the SLH intervention (appr. 11-14 weeks after T1). Primary study outcome: Change in physical capacity, assessed with the Six Minute Walking Test (6MWT). An a priori statistical power analysis calculation showed that the needed sample size is n=78 study participants and including an expected drop-out-rate of 20%, an overall total sample of n=100 study participants is needed. In the power analysis, the investigators considered data from previous studies on the primary study outcome, 6MWT distance, with a minimal important difference of ≥ 30 m, with the final calculation based on findings from our previous RCT on singing for COPD with a pre-post difference of mean 13.1±36.3 m after 10 weeks of singing in PR for COPD. Statistical power analysis calculations (primary study outcome: 6MWD): Estimated sample size for two-sample comparison of means: Test H0: n1 = n2, where n1 is the mean in population 1 and n2 is the mean in population 2. Assumptions: α (two-tailed) 0.05, β 0.2; Effect size Group 1: 15 m; Group 2: 5 m (SD 15). Estimated required sample sizes (based on power: 80 %): n1 = 52; n2 = 26

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

Patients who display persistent symptoms 6-18 months (+/- one month) after surgical resection of localised lung cancer with video-assisted thoracoscopy (VATS) will be invited to participate in the study.

Inclusion criteria

for the study include:

  • Persistent symptoms, i.e., an EORTC-QLQ-C30 symptom domain score (in any item) of ≥2 (="clinically relevant symptom or problem that should have healthcare professional attention"),
  • Surgery for stage I lung cancer 6-18 months (+/- one month) earlier,
  • Motivated for participating in the project (and acceptance of randomisation procedure),
  • Access to a computer or a tablet with internet access,
  • Ability to speak and understand Danish,
  • Acceptance of the scheduled times of the singing intervention twice a week.

Exclusion criteria

Exclusion criteria

include:

  • Unstable coronary diseases,
  • Severe cognitive disabilities (e.g., dementia),
  • Indication for adjuvant chemotherapy or other antineoplastic therapy,
  • Signs of lung cancer recurrence at regular follow-up CT scan.

No previous singing experience or musical competence is required. Participants will be informed that they are allowed to participate in additional offer of structured or unstructured offer physical exercise training and/or singing along with the project.

Treatment and study plan

Singing training (Singing for Lung Health (SLH))

Behavioral

10 weeks of singing training (conducted according to the Singing for Lung Health (SLH) approach). The singing training will be delivered online (1 1/2 hour twice a week) by professional singing teachers specifically trained and experienced within SLH. Sessions include physical, vocal, and breathing exercises and musical repertoire. Besides, movement, dancing, and artefacts for playful games are included along with singing. Each session consists of 20 min physical warm-ups, 20 min vocal warm-up with rhythm and pitch games, 40 min singing (incl. break), and 10 min cool-down.

Control Group: usual care

Behavioral

The control group will receive usual care, i.e., no specific additional intervention above those which the person usually engages with.

Primary outcomes

  1. Change in Physical capacity

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    Assessed with the Six Minute Walking Test (6MWT) (assessor-collected) , measured in meters walked in 6 minutes. Minimal important difference: >30 m.

  2. Perceived exertion

    Time frame: Changes measured before and after performance of 6MWT; Changes pre-post 10 weeks (measured at all assessment points).

    Measured using BORG CR-10 dyspnoea scale (self-reported). The scale ranges from 0 to 10 points, where 0 represents no exertion/dyspnoea and 10 represents maximal exertion/dyspnoea. Minimal important difference: 1 point.

  3. Change in Health-related quality of life (HRQoL)

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    St. George's Respiratory Questionnaire (SGRQ) (self-reported questionnaire). SGRQ has 50 items with 76 weighted responses and four scores: Total, Symptom, Activity, Impact. Each score ranges from 0 to 100, with 100 representing worst possible health status and 0 best possible. Minimal important differnence: -4 units.

Secondary outcomes

  1. Change in Quality of life

    Time frame: Pre-post 10 weeks

    EORTC 30 item Quality of Life Questionnaire (QLQ-C30), v. 3.0 (self-reported questionnaire). Functional domains: Physical function, role functioning, emotional function, cognitive function, social function. QLQ-C30 has 30 items: 1-28 completed on a 4-point Likert scale (1=not at all, 2=a little, 3=quite a bit, and 4=very much); 29-30 completed on a 7-point scale defined by extremes (1=very poor, 7=excellent). Raw and transformed scores are calculated, based on instructions in the QLQ-C30 scoring manual. Calculated scores range: 0-100. For the Functional scale, 100 = highest possible level of functioning. Cutoffs for clinically important problems: based on EORTC Quality of Life Group (Physical functioning (≤83), role functioning (≤58), emotional functioning (≤71), cognitive functioning (≤75), social functioning (≤58))

  2. Change in Symptoms burden

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    EORTC 30 item Quality of Life Questionnaire (QLQ-C30), v. 3.0 (self-reported). Symptom domains: Fatigue, nausea/vomiting, pain, sleep disturbances, dyspnoea, appetite loss, constipation, diarrhea, financial concerns. QLQ-C30 has 30 items: For 1-28: 4-point Likert scale (1=not at all, 2=a little, 3=quite a bit, 4=very much); for 29-30: 7-point scale defined by extremes (1=very poor, 7=excellent). Raw and transformed scores are calculated, based on the QLQ-C30 scoring manual. Calculated scores range: 0-100. For the Symptom scale, 100 = highest possible symptom burden. Cutoffs for clinically important problems: EORTC Quality of Life Group: Fatigue (≥39), nausea/vomiting (≥8), pain (≥25), insomnia (≥50), dyspnoea (≥17), appetite loss (≥50), constipation (≥50), diarrhea (≥17), financial concerns (≥17). Danish Multi-disciplinary Cancer Groups: ≥2 = "clinically relevant symptom"; ≥3 = "severe/serious symptom" (pain, dyspnoea, nausea/vomiting: ≥2 = "severe/serious symptom").

  3. Change in symptoms burden

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    EORTC Quality of Life Lung Cancer Module Questionnaire (QLQ-LC13) is a supplementary lung cancer-specific questionnaire to be used in conjunction with the QLQ-C30. Both questionnaires developed and validated in patients with lung cancer (self-reported). The module consists of 13 items and comprises multi- and single-item measures of lung cancer-associated symptoms (i.e. coughing, haemoptysis, dyspnoea and pain). Scaling of items: 1 (Not at all) to 4 (Very much). Scoring: 0 to 100. (higher scores = increasing symptom levels. Minimal important difference not defined.

  4. Change in symptoms burden: Dyspnoea

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    mMRC (Modified Medical Research Council Dyspnoea Scale) (self-reported). The scale includes scores from 0-4, with grade 0 corresponding to "Dyspnoea only when strenuous exercise" and grade 4 corresponding to "Too dyspneic to leave house or breathless when dressing. Minimal important difference: 1 point.

  5. Change in symptoms burden: Breathing vigilance

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    The Breathing Vigilance Questionnaire (Breathe-VQ) quantifies breathing vigilance in individuals with respiratory diseases and dysfunctional breathing (self-reported). The questionnaire utilises a 5 point Likert scale (1 = "never" to 5 = "always"), with a brief introductory text followed by instructions for scoring 1. Respondents select the response that best describes their typical breathing perceptions, and higher scores indicates higher levels of breathing vigilance. Minimal important difference has not yet been defined.

  6. Change in symptoms of anxiety and depression

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    Assessed with Hospital Anxiety and Depression Scale (HADS) (self-reported). HADS comprises 14 items, seven related to anxiety and seven related to depression. Minimal important difference: 1.32 (anxiety component) and 1.40 (depression component).

  7. Change in airway physiology

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    Reversibility test using a spirometer (assessor-collected): FEV1 in litres and % predicted, FVC in litres and % predicted, FEV1%/FVC%. Values will be categorised according to Global Initiative for Chronic Obstructive Lung Disease (GOLD): FEV1% > 80 = GOLD 1 (mild); 50 ≤ FEV1% < 80 = GOLD 2 (moderate); 30 ≤ FEV1% < 50 = GOLD 3 (severe); FEV1% < 30 = GOLD 4 (very severe). Reference values: height, age, sex and ethnicity. Minimal important difference for FEV1 is considered to be 120 ml.

  8. Change in aerobic fitness/Maximal oxygen uptake

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    VO2-max (test for VO2 max estimate; 70% of maximum heart rate for 20 minutes continuously). Women: 4-minute warm-up at 10 W, followed by an incremental ramp test with a workload increase of 10 W·min-¹. Men: 4-minute warm-up at 15 W, followed by an incremental ramp test with a workload increase of 15 W·min-¹.

    Criteria for Exhaustion: Respiratory exchange ratio (RER) ≥ 1.10; Cadence < 70 rpm despite verbal encouragement. Analysis: VO₂peak defined as the highest 30-second averaged VO₂ value obtained during the test; Incremental peak power output (iPPO) defined as the peak workload attained during the ramp test. Units of measure: Absolute VO₂peak: ml O2/min; Relative VO₂peak: ml O2/min/kg; iPPO: W.

  9. Change in inspiratory and expiratory pressure

    Time frame: Pre-post VO2 max test; pre-post 10 weeks (at all assessment points)

    Maximal inspiratory and expiratory pressure (MIP and MEP), measured in cm H2O.

  10. Change in Heart rate

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    Maximum pulse and recovery after 6MTW. Minimal important difference is considered as a 10% change.

  11. Adherence and drop-out

    Time frame: Registred during and after 10 weeks (at all assessment points).

    Continuously registered by the singing teachers and study nurses. Adherence rate will be divided into four categories (quartiles) with high adherence = ≥75% of all sessions.

  12. Adverse events

    Time frame: Post 10 weeks (registered at assessment point 2 (and 3 for Group 2).

    Any adverse events (adverse events (AE) and serious adverse events (SAE)).

Other outcomes

  1. Resting blood samples

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    Blood Cells: Hemoglobin (Hb) (mmol/L); Hematrocrit (Hct) (L/L or %); Thrombocytes (x109/L); Leukocyte differential count: (x109/L). Kidney function: eGFR (mL/min/1,73m2). Liver function: ASAT (U/L); ALAT (U/L); ALB (U/L); ALP (g/L). Metabolic function: Lactate dehydrogenase (LDH), mmol/L. Stress response: Epinephrine (Adrenaline) (nmol/L); Norepinephrine (Noradrenaline) (nmol/L); Dopamin (nmol/L). Inflammation and inflammatory drivers: C-reactive protein (CRP) (mg/L); Inflammatory cytokines (TNF-α, IL-1β, IL-6) (pg/mL); JAK2V617F mutation.

  2. Acute physiological response to maximal exercise (VO2max)

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    Metabolic markers: Lactate (mmol/L). Acid-base markers: pH; Partial pressure of carbon dioxide (pCO2) (mmHg); Bicarbonate (HCO3)(mmol/L). Oxygenation: Partial pressure of oxygen (pO2) (mmHg); Oxygen saturation (SaO2/SpO2) (%). Electrolyte and Ion Home: Potassium (mmol/L).

  3. Peripheral oxygenation

    Time frame: Changes pre-post 10 weeks (measured at all assessment points).

    Peripheral oxygenation (SpO2) (pulse oximeter).

Study contacts

Contact information is provided by the study sponsor or research team.

Mette Kaasgaard, PhD

CONTACT

[email protected]

4528940238

Uffe Bødtger, PhD

CONTACT

[email protected]

4526791426

Sponsors and collaborators

Lead sponsor

Zealand University Hospital

Other

Registry information

Official study title

Effects and Mechanisms of Online Delivered Singing Training vs Usual Care in Patients With Persistent Symptoms 6-18 Months After Surgical Resection for Non-small Cell Lung Cancer (NSCLC) - a Multi-centre RCT

Acronym: Sing-a-Lung 2

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Mar 10, 2026
Registry last updated
Apr 2, 2026

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

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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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