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

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ClinicalTrials.gov Identifier: NCT04067830
Recruitment Status : Recruiting
First Posted : August 26, 2019
Last Update Posted : December 2, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 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 Other: Best Practice Procedure: Laparoscopic Surgery Other: Quality-of-Life Assessment Other: Questionnaire Administration Device: Respiratory Muscle Training Device Procedure: Video-Assisted Thoracic Surgery Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Preoperative Respiratory Muscle Training to Prevent Postoperative Pulmonary Complications in Patients Undergoing Resection for Lung Cancer
Actual Study Start Date : January 22, 2019
Estimated Primary Completion Date : January 22, 2023
Estimated Study Completion Date : January 22, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

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: 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

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Procedure: Video-Assisted Thoracic Surgery
Undergo video-assisted thoracic surgery
Other Name: 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: 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

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Device: Respiratory Muscle Training Device
Use power lung device to complete RMT

Procedure: Video-Assisted Thoracic Surgery
Undergo video-assisted thoracic surgery
Other Name: VATS




Primary Outcome Measures :
  1. Change in inspiratory and expiratory muscle strength [ Time Frame: Baseline up to 12 months ]
    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.

  2. Change in pulmonary function and respiratory muscle endurance [ Time Frame: Baseline up to 12 months ]
    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.

  3. Change in peak exercise capacity (VO2peak) [ Time Frame: Baseline up to 12 months ]
    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.


Secondary Outcome Measures :
  1. Metabolic and muscle physiology marker analysis [ Time Frame: At time of surgical resection ]
    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.

  2. Gene expression ribonucleic acid (RNA) extraction, reverse transcription, and real-time quantitative polymerase chain reaction (PCR) analysis [ Time Frame: At time of surgical resection ]
    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.

  3. Change in quality of life (QoL) [ Time Frame: Baseline up to 12 months ]
    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.

  4. Change in QoL [ Time Frame: Baseline up to 12 months ]
    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.

  5. Change in fatigue level [ Time Frame: Baseline up to 12 months ]
    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.

  6. Change in sleepiness (sleep apnea) [ Time Frame: Baseline up to 12 months ]
    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.

  7. Change in sleepiness (sleep apnea) [ Time Frame: Baseline up to 12 months ]
    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.

  8. Change in sleep quality [ Time Frame: Baseline up to 12 months ]
    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.

  9. Change in anxiety and depression [ Time Frame: Baseline up to 12 months ]
    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.

  10. Change in dyspnea [ Time Frame: Baseline up to 12 months ]
    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.

  11. Presence or absence of pneumonia diagnoses [ Time Frame: Up to 12 months ]
    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.


Other Outcome Measures:
  1. Total hospital length of stay (LOS) [ Time Frame: Up to 12 months ]
    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).

  2. Total intensive care unit LOS [ Time Frame: Up to 12 months ]
    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).

  3. Pre-operative LOS [ Time Frame: From date of admission to the date of surgery ]
    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).

  4. Lung infection rates [ Time Frame: Up to 12 months ]
    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.

  5. Identified molecular marker analysis [ Time Frame: Up to 1 month post-surgery ]
    Analysis of identified molecular markers will be completed to correlate with patient outcome and potentially differentiate responders from non-responders.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented stage I-IIIb lung cancer
  • Participant is able to speak, read, and comprehend English
  • Participant must be undergoing either video-assisted thoracic surgery (VATS or robotic surgery) or laparoscopic surgery for curative intent lung resection
  • Have the following pulmonary function values:

    • Forced expiratory volume in 1 second (FEV1) < 60% (% predicted) and/or,
    • Diffusion capacity of the lung for carbon monoxide (DLCO) < 60% of predicted
    • Note: Patients with moderate-to-severe airflow obstruction will be chosen because they are at the greatest risk for complications and also demonstrate the greatest benefits associated with RMT
  • Patients with or without neoadjuvant chemoradiotherapy (CRT) prior to surgery will be included
  • Ability to follow written and verbal instructions
  • Participant must be available for a minimum of 2 weeks prior to scheduled surgical resection
  • Participant or legal representative 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04067830


Locations
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United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Saikrishna S. Yendamuri    716-845-8675    Sai.Yendamuri@RoswellPark.org   
Principal Investigator: Saikrishna S. Yendamuri         
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Saikrishna S Yendamuri Roswell Park Cancer Institute

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Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT04067830     History of Changes
Other Study ID Numbers: I 72818
NCI-2019-03537 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 72818 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
R01CA222382 ( U.S. NIH Grant/Contract )
First Posted: August 26, 2019    Key Record Dates
Last Update Posted: December 2, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases