Respiratory Muscle Training Before Surgery in Preventing Lung Complications in Patients With Stage I-IIIB Lung Cancer

Preoperative Respiratory Muscle Training to Prevent Postoperative Pulmonary Complications in Patients Undergoing Resection for Lung Cancer

This phase II trial studies how well respiratory muscle training before surgery works in preventing lung complications after surgery in patients with stage I-IIIB lung cancer. Patients with lung cancer who choose to undergo surgical resection often have complications after surgery such as pneumonia, unplanned intubations, difficulty breathing and reduced physical functioning, and increased medical costs and a reduced quality of life. Improving pre-surgical pulmonary health through respiratory muscle training may improve respiratory muscle strength, response to surgery, and quality of life after surgery in patients with lung cancer.

Study Overview

• Status: Recruiting
• Conditions: Stage II Lung Cancer AJCC v8; Stage IIA Lung Cancer AJCC v8; Stage IIB Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage I Lung Cancer AJCC v8; Stage IA1 Lung Cancer AJCC v8; Stage IA2 Lung Cancer AJCC v8; Stage IA3 Lung Cancer AJCC v8; Stage IB Lung Cancer AJCC v8
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Other: Best Practice; Procedure: Laparoscopic Surgery; Procedure: Video-Assisted Thoracic Surgery; Device: Respiratory Muscle Training Device

Detailed Description

PRIMARY OBJECTIVES:

I. Assess the impact of a short-duration respiratory muscle training (RMT) program on respiratory muscle strength in patients undergoing resection for lung cancer.

SECONDARY OBJECTIVES:

I. Compare the extent of diaphragm atrophy and catabolic/anabolic pathway activation between RMT responders and non-responders evaluated for gene expression and candidate and candidate causative protein levels.

II. Determine the effect of the short-duration RMT program on health related quality-of-life measures.

III. Assess the impact of the short-duration RMT program on postoperative outcomes.

EXPLORATORY OBJECTIVES:

I. Determine the financial sustainability of a transitional home-based prehabilitation program targeting respiratory muscle weakness prior to lung resection.

II. Analysis of molecular markers to correlate with patient outcome and potentially differentiate responders from non-responders.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (USUAL CARE): Patients receive usual care consisting of physical therapy once weekly, receiving pre-surgical information, instruction on the use of a spirometer device, and wearing a Fitbit to track activity. Patients then undergo video-assisted thoracic surgery or laparoscopic surgery. Patients continue to track activity using the Fitbit for 3 months post-surgery.

ARM II (RMT + USUAL CARE): Patients use a power lung device to complete 3 sets of 15 RMT exercises over 30 minutes 6 days per week over 2-4 weeks for a minimum of 12 sessions prior to surgery. Patients also receive usual care consisting of physical therapy once weekly, receiving pre-surgical information, instruction on the use of a spirometer device, and wearing a Fitbit to track activity. Patients then undergo video-assisted thoracic surgery or laparoscopic surgery. Patients continue to track activity using the Fitbit for 3 months post-surgery.

After completion of study, patients are followed up at 1, 3, 6, and 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
      • Principal Investigator: Saikrishna S. Yendamuri
      • Contact: Saikrishna S. Yendamuri; Phone Number: 716-845-8675; Email: Sai.Yendamuri@RoswellPark.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented stage I-IIIb lung cancer or is undergoing surgery for diagnosis
• Participant is able to speak, read, and comprehend English
• Participant must be undergoing or is anticipated to either video-assisted thoracic surgery (VATS or robotic surgery) or laparoscopic surgery for curative intent lung resection
• Patients with or without neoadjuvant chemoradiotherapy (CRT) prior to surgery will be included
• Ability to follow written and verbal instructions
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Documented ischemic heart disease; congestive heart failure or; significant cardiac arrhythmias that would exclude them from having surgery
• Overall medical frailty (clinician discretion) or ECOG > 2
• Pregnant or nursing female participants
• Unwilling or unable to follow protocol requirements
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to participate in this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (usual care); Patients receive usual care consisting of physical therapy once weekly, receiving pre-surgical information, instruction on the use of a spirometer device, and wearing a Fitbit to track activity. Patients then undergo video-assisted thoracic surgery or laparoscopic surgery. Patients continue to track activity using the Fitbit for 3 months post-surgery.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Best Practice; Receive usual care; Other Names: standard of care; standard therapy; Procedure: Laparoscopic Surgery; Undergo laparoscopic surgery; Other Names: laparoscopic-assisted resection; laparoscopy-assisted surgery; Procedure: Video-Assisted Thoracic Surgery; Undergo video-assisted thoracic surgery; Other Names: VATS
Experimental: Arm II (RMT + usual care); Patients use a power lung device to complete 3 sets of 15 RMT exercises over 30 minutes 6 days per week over 2-4 weeks for a minimum of 12 sessions prior to surgery. Patients also receive usual care consisting of attending physical therapy once weekly, receiving pre-surgical information, instruction on the use of a spirometer device, and wearing a Fitbit to track activity. Patients then undergo video-assisted thoracic surgery or laparoscopic surgery. Patients continue to track activity using the Fitbit for 3 months post-surgery.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Best Practice; Receive usual care; Other Names: standard of care; standard therapy; Procedure: Laparoscopic Surgery; Undergo laparoscopic surgery; Other Names: laparoscopic-assisted resection; laparoscopy-assisted surgery; Procedure: Video-Assisted Thoracic Surgery; Undergo video-assisted thoracic surgery; Other Names: VATS; Device: Respiratory Muscle Training Device; Use power lung device to complete RMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in inspiratory and expiratory muscle strength	Will be treated as a continuous variable and will be summarized by treatment group and time-point using the mean, median, standard deviation, and the appropriate percentiles. The effectiveness of the respiratory muscle training (RMT) program on each respiratory outcome will be assessed by comparing the preoperative change between groups using an analysis of covariance (ANCOVA) model, with an adjustment for the pretreatment levels. For each outcome, the preoperative change (T1-T0) will be modeled as a function of treatment group (RMT versus usual care) and pre-treatment levels. A one-sided Wald type-test about coefficient for treatment group will evaluate whether the RMT program had a beneficial impact on the given respiratory outcome. All model assumptions will be verified graphically using quantile-quantile and residual plots. Transformations will be applied as appropriate.	Baseline up to 12 months
Change in pulmonary function and respiratory muscle endurance	Will be treated as a continuous variable and will be summarized by treatment group and time-point using the mean, median, standard deviation, and the appropriate percentiles. The effectiveness of the RMT program on each respiratory outcome will be assessed by comparing the preoperative change between groups using an ANCOVA model, with an adjustment for the pretreatment levels. For each outcome, the preoperative change (T1-T0) will be modeled as a function of treatment group (RMT versus usual care) and pre-treatment levels. A one-sided Wald type-test about coefficient for treatment group will evaluate whether the RMT program had a beneficial impact on the given respiratory outcome. All model assumptions will be verified graphically using quantile-quantile and residual plots. Transformations will be applied as appropriate.	Baseline up to 12 months
Change in peak exercise capacity (VO2peak)	Will be treated as a continuous variable and will be summarized by treatment group and time-point using the mean, median, standard deviation, and the appropriate percentiles. The effectiveness of the RMT program on each respiratory outcome will be assessed by comparing the preoperative change between groups using an ANCOVA model, with an adjustment for the pretreatment levels. For each outcome, the preoperative change (T1-T0) will be modeled as a function of treatment group (RMT versus usual care) and pre-treatment levels. A one-sided Wald type-test about coefficient for treatment group will evaluate whether the RMT program had a beneficial impact on the given respiratory outcome. All model assumptions will be verified graphically using quantile-quantile and residual plots. Transformations will be applied as appropriate.	Baseline up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic and muscle physiology marker analysis	Assays of muscle biopsies will be performed for metabolic and muscle physiology markers. The correlative markers will be compared between RMT responders, RMT non-responders, and usual care (control) in a pairwise fashion using Holm-Bonferroni adjusted t-tests. Responders will be those who present with a > 15% increase in inspiratory and expiratory muscle strength. The gene-level raw count values of micro ribonucleic acid (mRNA)s will be analyzed with the edgeR Bioconductor package in R, first for normalization with the trimmed mean of M-values method, and then for comparison of expression between treatments using generalized linear models with negative binomial distribution and a likelihood ratio test to generate p values. False discovery rates (FDR) will be estimated from p-values with the Benjamini-Hochberg method, and mRNAs/genes with FDR < 0.05 and fold-change values of >= 1 log2 unit will be considered as differentially expressed.	At time of surgical resection
Gene expression ribonucleic acid (RNA) extraction, reverse transcription, and real-time quantitative polymerase chain reaction (PCR) analysis	Assays of muscle biopsies will be performed for gene expression of RNA extraction, reverse transcription and real-time PCR. The correlative markers will be compared between RMT responders, RMT non-responders, and usual care (control) in a pairwise fashion using Holm-Bonferroni adjusted t-tests. Responders will be those who present with a > 15% increase in inspiratory and expiratory muscle strength. The gene-level raw count values of mRNAs will be analyzed with the edgeR Bioconductor package in R, first for normalization with the trimmed mean of M-values method, and then for comparison of expression between treatments using generalized linear models with negative binomial distribution and a likelihood ratio test to generate p values. FDR will be estimated from p-values with the Benjamini-Hochberg method, and mRNAs/genes with FDR < 0.05 and fold-change values of >= 1 log2 unit will be considered as differentially expressed.	At time of surgical resection
Change in quality of life (QoL)	Will be measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) - Core (C)30. The QoL measures are treated as continuous and will be summarized by treatment group and time-point using the mean, median, standard deviation, and the appropriate percentiles. The change in QoL measures (from baseline) will be modeled as a function of treatment group, time-point, their two-way interaction, and baseline levels using a general linear model. Comparisons of QoL at each time-point will utilize Holm-Bonferroni adjusted tests about the appropriate contrasts of model estimates. All model assumptions will be verified graphically using quantile-quantile and residual plots. Transformations will be applied as appropriate.	Baseline up to 12 months
Change in QoL	Will be measured by EORTC QLQ - Lung Cancer 13. The QoL measures are treated as continuous and will be summarized by treatment group and time-point using the mean, median, standard deviation, and the appropriate percentiles. The change in QoL measures (from baseline) will be modeled as a function of treatment group, time-point, their two-way interaction, and baseline levels using a general linear model. Comparisons of QoL at each time-point will utilize Holm-Bonferroni adjusted tests about the appropriate contrasts of model estimates. All model assumptions will be verified graphically using quantile-quantile and residual plots. Transformations will be applied as appropriate.	Baseline up to 12 months
Change in fatigue level	Will be measured by Functional Assessment of Chronic Illness Therapy Fatigue. The QoL measures are treated as continuous and will be summarized by treatment group and time-point using the mean, median, standard deviation, and the appropriate percentiles. The change in QoL measures (from baseline) will be modeled as a function of treatment group, time-point, their two-way interaction, and baseline levels using a general linear model. Comparisons of QoL at each time-point will utilize Holm-Bonferroni adjusted tests about the appropriate contrasts of model estimates. All model assumptions will be verified graphically using quantile-quantile and residual plots. Transformations will be applied as appropriate.	Baseline up to 12 months
Change in sleepiness (sleep apnea)	Will be measured by the Epworth Sleepiness Scale. The QoL measures are treated as continuous and will be summarized by treatment group and time-point using the mean, median, standard deviation, and the appropriate percentiles. The change in QoL measures (from baseline) will be modeled as a function of treatment group, time-point, their two-way interaction, and baseline levels using a general linear model. Comparisons of QoL at each time-point will utilize Holm-Bonferroni adjusted tests about the appropriate contrasts of model estimates. All model assumptions will be verified graphically using quantile-quantile and residual plots. Transformations will be applied as appropriate.	Baseline up to 12 months
Change in sleepiness (sleep apnea)	Will be measured by the Stop-Bang Questionnaire. The QoL measures are treated as continuous and will be summarized by treatment group and time-point using the mean, median, standard deviation, and the appropriate percentiles. The change in QoL measures (from baseline) will be modeled as a function of treatment group, time-point, their two-way interaction, and baseline levels using a general linear model. Comparisons of QoL at each time-point will utilize Holm-Bonferroni adjusted tests about the appropriate contrasts of model estimates. All model assumptions will be verified graphically using quantile-quantile and residual plots. Transformations will be applied as appropriate.	Baseline up to 12 months
Change in sleep quality	Will be measured by Pittsburgh Sleep Quality Index. The QoL measures are treated as continuous and will be summarized by treatment group and time-point using the mean, median, standard deviation, and the appropriate percentiles. The change in QoL measures (from baseline) will be modeled as a function of treatment group, time-point, their two-way interaction, and baseline levels using a general linear model. Comparisons of QoL at each time-point will utilize Holm-Bonferroni adjusted tests about the appropriate contrasts of model estimates. All model assumptions will be verified graphically using quantile-quantile and residual plots. Transformations will be applied as appropriate.	Baseline up to 12 months
Change in anxiety and depression	Will be measured by Hospital Anxiety and Depression Scale. The QoL measures are treated as continuous and will be summarized by treatment group and time-point using the mean, median, standard deviation, and the appropriate percentiles. The change in QoL measures (from baseline) will be modeled as a function of treatment group, time-point, their two-way interaction, and baseline levels using a general linear model. Comparisons of QoL at each time-point will utilize Holm-Bonferroni adjusted tests about the appropriate contrasts of model estimates. All model assumptions will be verified graphically using quantile-quantile and residual plots. Transformations will be applied as appropriate.	Baseline up to 12 months
Change in dyspnea	Will be measured by the Borg Dyspnea Scale. The QoL measures are treated as continuous and will be summarized by treatment group and time-point using the mean, median, standard deviation, and the appropriate percentiles. The change in QoL measures (from baseline) will be modeled as a function of treatment group, time-point, their two-way interaction, and baseline levels using a general linear model. Comparisons of QoL at each time-point will utilize Holm-Bonferroni adjusted tests about the appropriate contrasts of model estimates. All model assumptions will be verified graphically using quantile-quantile and residual plots. Transformations will be applied as appropriate.	Baseline up to 12 months
Presence or absence of pneumonia diagnoses	Pneumonia status is treated as dichotomous data and will be summarized by treatment group using frequencies and relative frequencies. The pneumonia rates will be compared between treatment groups using a one-sided Fisher exact test, as we expect the RMT program to reduce rates.	Up to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total hospital length of stay (LOS)	Will be treated as continuous data and will be summarized by treatment group using the mean, median, standard deviation, and the appropriate percentiles. Comparisons between treatment groups will be made using one-sided t-tests or Mann-Whitney U tests (as appropriate).	Up to 12 months
Total intensive care unit LOS	Will be treated as continuous data and will be summarized by treatment group using the mean, median, standard deviation, and the appropriate percentiles. Comparisons between treatment groups will be made using one-sided t-tests or Mann-Whitney U tests (as appropriate).	Up to 12 months
Pre-operative LOS	Will be treated as continuous data and will be summarized by treatment group using the mean, median, standard deviation, and the appropriate percentiles. Comparisons between treatment groups will be made using one-sided t-tests or Mann-Whitney U tests (as appropriate).	From date of admission to the date of surgery
Lung infection rates	Lung infection will be treated as dichotomous data and will be summarized by treatment group using frequencies and relative frequencies. Comparison of infection rates between treatment groups will be made using Fisher?s exact test.	Up to 12 months
Identified molecular marker analysis	Analysis of identified molecular markers will be completed to correlate with patient outcome and potentially differentiate responders from non-responders.	Up to 1 month post-surgery

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Saikrishna S Yendamuri, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2019
• Primary Completion (Estimated): March 22, 2025
• Study Completion (Estimated): March 22, 2026

Study Registration Dates

• First Submitted: August 21, 2019
• First Submitted That Met QC Criteria: August 21, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: I 72818 (Other Identifier: Roswell Park Cancer Institute); NCI-2019-03537 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA222382 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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