Lung Cancer Rehabilitation After Medical Treatment

Study Overview
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Brief Summary
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Lung cancer is the leading cause of cancer death worldwide and associated with high disease burden, symptoms and poor health-related quality of life (HRQoL). Lung cancer is the most commonly diagnosed type of cancer in China (with rates rising due to the smoking incidence) and is the leading cause of cancer-related death. The burden is on patients, families, the healthcare system and society, and will continue to rise into the future. The full impact of this in China has not yet occurred. New strategies are urgently required to improve survivorship. This multi-site, assessor blinded, two-arm superiority randomised controlled trial, conducted at two hospitals in China, aims to test the effect of exercise rehabilitation, compared to usual care (no exercise rehabilitation) on HRQoL and functional outcomes in 150 patients treated for lung cancer. The primary hypothesis is that exercise rehabilitation will be superior to usual care, in improving HRQoL at 12-weeks (post program). Secondary aims include measuring the effectiveness of exercise rehabilitation, compared to usual care on function, physical activity, symptoms, mood, sleep and program costs. Faecal samples (500mg) will be collected before and after the intervention.

Detailed Description
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Lung cancer is the leading cause of cancer death worldwide and associated with high disease burden, symptoms and poor health-related quality of life (HRQoL). Lung cancer is the most commonly diagnosed type of cancer in China (with rates rising due to the smoking incidence) and is the leading cause of cancer-related death. The burden is on patients, families, the healthcare system and society, and will continue to rise into the future. The full impact of this in China has not yet occurred. New strategies are urgently required to improve survivorship. This multi-site, assessor blinded, two-arm superiority randomized controlled trial, conducted at two hospitals in China, aims to test the effect of exercise rehabilitation, compared to usual care (no exercise rehabilitation) on HRQoL and outcomes including physical function in 150 patients treated for lung cancer. The primary hypothesis is that exercise rehabilitation will be superior to usual care, in improving HRQoL at 12-weeks (post program). Secondary aims include include measuring the effectiveness of exercise rehabilitation, compared to usual care on function, physical activity, symptoms, mood, sleep and program costs. One hundred and fifty patients with stage I-IIIA non-small cell lung cancer (NSCLC) 4-12 weeks following completion of treatment (including surgery with or without adjuvant therapy) and life expectancy greater than 6 months will be recruited from the affiliated hospital of Nantong University and the first affiliated hospital of Nanjing Medical University. At recruitment participants provide written informed consent, complete baseline assessment and to ensure concealment of allocation participants will be randomly allocated off-site to one of two arms (1:1 ratio). The intervention programs start following randomization and will continue for 12 weeks duration. Trained physiotherapists will provide the intervention. Patients in both arms will receive usual medical, physiotherapy and nursing care according to usual protocols. This does not involve exercise rehabilitation or advice. Additionally patients in intervention group (exercise rehabilitation) will receive a multimodal program which includes a 90 minute program at the hospital gymnasium in a supervised environment a minimum of once but up to twice per week. Rehabilitation will include aerobic (brisk walking) and resistance training and 30 minutes of 8 style Tai Chi). Participants will be advised to walk on days of non-attendance - this will be individualized with the aim to have participants increase to 30 minutes walking per day. Assessments will be conducted at baseline and then by blinded assessors at 12 weeks and 6 months post-baseline. Survival will be followed-up and censored at 1 year. This important study brings together a strong collaborative research team spanning China and Australia, involving medical doctors, physiotherapists and academics. The topic is important, novel and will generate clinically meaningful research for an international audience, aiming to improve the survivorship quality of patients with lung cancer. The gut microbiome is a source of potentially disease-modifying bioactive metabolites and has recently been suggested to contribute to the pathogenesis of a variety of disorders. Therefore, we will study the gut microbiota and metabolites of the participants in order to identify potential the biomarkers for the clinical outcomes. Fresh faecal samples will be collected from all individuals before group assignment and after the completion of the program. The written informed consent will be provided by the participants. Specifically, faecal samples (500mg) will be collected from participants who are free from gastrointestinal conditions, with no antibiotic exposure in the 28 days prior to sample collection. 'Snap' frozen samples will be stored at -80°C until the time of DNA extractions, 16S rDNA sequencing, and mass spectrometry analysis of the faecal metabolites. The distribution of gut microbiota before and after exercise will be compared and analyzed to obtain the species of bacterial flora that changed significantly after exercise. Moreover, the gut metabolites that changed significantly before and after exercise will be used to explore the biomarkers for the curative effect of rehabilitation exercise, as well as their relationships with the differentially distributed gut microbiota.

Official Title
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The Effectiveness of Rehabilitation for Patients With Lung Cancer in China: a Randomised Controlled Trial

Conditions
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Lung Neoplasms

Intervention / Treatment
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* Other: Intervention (rehabilitation exercise)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with non-small cell lung cancer (NSCLC) 4-12 weeks following completion of treatment (surgery, chemotherapy, radiotherapy, immunotherapy); Physician/doctor approval; Physician rated life expectancy greater than 6 months; Informed consent; Eastern Cooperate Oncology Group (ECOG) performance status of 0-2 at study entry; Not meeting physical activity/exercise guidelines. Exclusion Criteria: Unstable psychiatric/cognitive disorder; Comorbidity preventing exercise; ECOG performance status of 3 or 4 at study entry.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Design: Two-site, assessor blinded, two-arm superiority randomised controlled trial. Setting: Participant recruitment from the affiliated hospital of Nantong University and the first affiliated hospital of Nanjing Medical University Procedure: Randomisation: Randomisation list devised by independent statistician; carried out using the REDCap randomisation function to ensure allocation concealment. Following consent and assessment, participants are randomised 1:1. Lung cancer with stage I-IIIA and treatment type is surgery +/- adjuvant treatment.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual care(both arms)<br>Usual care (both arms): Patients in both arms will receive usual medical, physiotherapy and nursing care according to usual protocols. This does not involve exercise rehabilitation or advice. | |
| Experimental: Intervention (exercise rehabilitation)<br>Patients in intervention group (exercise rehabilitation) will receive a multimodal program which includes a 90 minute program at the hospital gymnasium in a supervised environment a minimum of once but up to twice per week. Rehabilitation will include aerobic (brisk walking), resistance training and 30 minutes of 8 style Tai Chi. Participants will be advised to walk on days of non-attendance - this will be individualised with the aim to have participants increase to 30 minutes walking per day. | Other: Intervention (rehabilitation exercise)<br>* Patients in intervention group (exercise rehabilitation) will receive a multimodal program which includes a 90 minute program at the hospital gymnasium in a supervised environment a minimum of once but up to twice per week. Rehabilitation will include aerobic (brisk walking), resistance training and 30 minutes of 8 style Tai Chi. Participants will be advised to walk on days of non-attendance - this will be individualised with the aim to have participants increase to 30 minutes walking per day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| European Organization for the Research and Treatment of Cancer questionnaire (EORTC QLQ-C30-LC13) | HRQoL will be assessed with the European Organization for the Research and Treatment of Cancer questionnaire (EORTC QLQ-C30-LC13) at baseline, 12 weeks and 6 months post-baseline. Score ranges from 0 100.For functional domains and global health status/quality of life scale, higher score means better status. While for symptom domains and single-items, lower scores represent less symptoms. | The primary time point is the change from baseline to 12 weeks. This outcome will also be measured at 6 months post-baseline. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Exercise Capacity | All participants will complete a Incremental Shuttle Walking Test following published guidelines. | 1) baseline, 2) 12 week, and 3) 6 months post-baseline. | 
| Seven-day Physical Activity | Will be measured objectively using an pedometer at baseline, 12 weeks and 6 months post-baseline. It is worn for 7 consecutive days and a minimum of four full days (8 hours/day) is required for valid analyses. | 1) baseline, 2) 12 weeks, and 3) 6 months post-baseline. | 
| Grip strength | A hand held dynamometry manual muscle test is a common, simple measurement of strength and has been used in many patient populations including cancer and is reliable and sensitive to change. We will measure hand grip strength bilaterally | 1) baseline, 2) 12 weeks, and 3) 6 months post-baseline. | 
| 30-Second Chair Stand | To test leg strength and endurance. A below average score indicates a risk for falls. | 1) baseline, 2) 12 weeks, and 3) 6 months post-baseline. | 
| International physical activity questionnaire(IPAQ) | The International Physical Activity Questionnaire (IPAQ) scores are categorised as high/moderate (meeting PA guidelines) or low (not meeting PA guidelines) and as a continuous energy expenditure score (metabolic equivalent of task (MET) minutes per week). Higher scores indicate increased PA. | 1) baseline, 2) 12 weeks, and 3) 6 months post-baseline. | 
| Self-Rating Anxiety Scale(SAS) | To test the anxiety level of the patients. It has 20 items and are four-point scale(rated 1-4), some of the items are reversely scored. Score ranges from 0 100, higher score means worse anxiety status. | 1) baseline, 2) 12 weeks, and 3) 6 months post-baseline. | 
| Self-Rating Depression Scale(SDS) | To test the depression level of the patients. It has 20 items and are four-point scale(rated 1-4), some of the items are reversely scored. Score ranges from 0 100, higher score means worse depression status. | 1) baseline, 2) 12 weeks, and 3) 6 months post-baseline. | 
| Pittsburgh Sleep Quality Index(PSQI) | Pittsburgh Sleep Quality Index(PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven component scores. The sum of scores for these seven components yields one global score, and the higher score means the worse sleep quality. Score ranges from 0 21, higher score means worse sleep quality. | 1) baseline, 2) 12 weeks, and 3) 6 months post-baseline. | 
| MD Anderson Symptom Inventory-lung cancer (MDASI-LC) | To evaluate to the severity and interference of the symptom in participants.The MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) will be used to measure symptom severity and distress. The symptom severity component comprises 13 core and three lung cancer specific items, measured on a 0-10 numerical rating scale. The average score is reported, with higher scores indicating worse symptoms. The MCID in lung cancer has been reported as being between 0.98 to 1.21 points | 1) baseline, 2) 12 weeks, and 3) 6 months post-baseline. | 
| Australia-modified Karnofsky Performance Status(AKPS) | To evaluate the performance of the whole well-being of the participants. Score ranges from 0 100, higher score means better status. | 1) baseline, 2) 12 weeks, and 3) 6 months post-baseline. | 
| European quality of life 5-dimension 5-level(EQ-5D-5L) | European quality of life 5-dimension 5-level(EQ-5D-5L) is a family of instruments to describe and value health. It comprises a short descriptive system questionnaire and a visual analogue scale that are cognitively undemanding. A value set provides values(weights) for each health state description according to the preferences of the general population of a country/region. | 1) baseline, 2) 12 weeks, and 3) 6 months post-baseline. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung cancer, exercise, rehabilitation, Tai Chi, health-related quality of life