Sustainability of Pulmonary Rehab Gains

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02241733
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 2
• Actual Duration (Months): 58.3
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

People with moderate to severe COPD trap air in their lungs. This lessens their ability to exercise. The investigators developed a computerized breathing retraining program to help patients empty their lungs during exercise. The investigators believe that learning to control breathing will help patients be more active. The purpose of this study is to test the effects of using breathing retraining (intervention group) versus no breathing retraining (control group) as part of a 12-week exercise program. The investigators are examining the long term effects of this training on exercise capacity and the ability to empty ones lungs during exercise. Patients will participate in a 12-week exercise program, with or without breathing retraining. They will then participate in a 42 week adherence program to maintain physical activity. Patient testing will be competed at baseline, 12 weeks, 6 months and 1 year. 250 patients with moderate to severe COPD will be enrolled.

Condition or Disease	Intervention/Treatment	Phase
COPD	Behavioral: Breathing retraining plus exercise; Behavioral: Exercise only	N/A

Detailed Description

Rationale: Development of dynamic hyperinflation is a primary limiting factor of exercise tolerance in chronic obstructive pulmonary disease (COPD). To lessen the development of dynamic hyperinflation, and to improve exercise tolerance in COPD patients, the investigators have developed a breathing-retraining technique to be used during pulmonary rehabilitation. This breathing-retraining technique is designed to decrease respiratory rate and prolong exhalation. The investigators demonstrated that, in the short-term, hyperinflation and exercise duration improved more with breathing-retraining plus exercise-training than with exercise-training alone. Because a crucial aspect of pulmonary rehabilitation is the maintenance its short-term benefits over the long-term, the investigators now propose to test whether short-term benefits of breathing-retraining plus exercise followed by an adherence-intervention program are sustainable over the long-term Primary Hypothesis: (H1) In COPD patients, improvements in exercise duration on a constant- load treadmill test will be greater after 12 weeks of breathing-retraining plus exercise-training followed by a 42-week adherence-intervention program (1 yr. total) than after 12 weeks of exercise-training alone followed by a 42-week adherence-intervention program (1 yr. total). Secondary Hypotheses: One year after randomization, exercise-induced dynamic hyperinflation will be less during a constant-load treadmill test (H2), 6-minute walking distance will be longer (H3), and mastery over breathing will be greater (H4) in the breathing-retraining plus exercise-training group than in the exercise-alone group. Lastly (exploratory objective), the investigators will assess the effect of the patient's physiologic, psychologic and clinical phenotype on short- term and long-term responsiveness to pulmonary rehabilitation.

Methods: The proposed study is a randomized, controlled clinical trial in which 250 patients with moderate-to-severe COPD will be enrolled. One hundred forty of these patients are expected to qualify for randomization into the breathing-retraining plus exercise-training group or the exercise-training alone group. Patients will receive 12-weeks of supervised training according to group assignment (three times weekly) followed by an adherence-intervention program (weekly phone motivational interviews, home-exercise program, and monthly laboratory booster sessions). Follow-up testing will be completed at 12 weeks, and at 6 and 12 months. Testing will include pulmonary function test, incremental-load and constant-load treadmill tests, 6-minute walk test, measurements of dyspnea, assessment of respiratory and quadriceps muscle strength and endurance and quadriceps ultrasonography. Analysis: In the principal analysis of the primary outcome measure (exercise duration; H1) the investigators will compare changes in exercise duration (constant work-rate treadmill test) from baseline to end of study using 2-sample t-test (two-tailed =.05). The primary analysis will be based on intention-to-treat principles. Multiple imputation will be used for study subjects missing the 12-month measurement. This imputation model will be based on baseline characteristics of study participants. Several secondary analyses of the primary outcome measure will be performed (H2-H4). Linear regression will be used to determine whether the observed treatment benefits persist after adjustment for baseline covariates and measures of adherence to treatment. Since several measurements will be taken on each patient, mixed-models analysis will be used to compare the changes on the constant-load treadmill test over time between the two groups.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Sustainability of Rehabilitation Gains in COPD
• Actual Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Oct 21, 2018
• Actual Study Completion Date: Aug 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: exercise Patients will exercise for 12 weeks and then participate in an adherence program	Behavioral: Exercise only; Patients will participate in a 12-week exercise program . They will also participate in an adherence program.
Experimental: exercise plus breathing retraining Patients will exercise plus breathing retraining for 12 weeks and then participate in an adherence program	Behavioral: Breathing retraining plus exercise; Patients will participate in a 12-week exercise program with breathing retraining. They will also participate in an adherence program.

Outcome Measures

Primary Outcome Measures

1. Duration of Exercise Time on a Constant Work-rate Treadmill Test [52 week test]

   Patients walk on a treadmill set at a constant workrate. The difference in the time walked on the treadmill from baseline to study completion is the primary outcome measure.

Secondary Outcome Measures

1. Inspiratory Capacity [52 week test]

   Inspiratory capacity is measured at a set time during the constant workrate treadmill test. The difference between the inspiratory capacity measured at baseline and 52 weeks is a secondary outcome. Inspiratory capacity measured during exercise is a measure of dynamic hyperinflation.

2. 6 Minute Walk Distance [52 weeks]

   Six-minute walk distance will be measured at 52 weeks. The difference in distance walked in meters between baseline and 52 weeks is the secondary outcome measure. The 6 minute walk is conducted using the guidelines issued by the American Thoracic Society.

3. Mastery Over Breathing [52 weeks]

   Mastery over breathing is measured using the Chronic Respiratory Disease Questionnaire. Specifically the subscale 'mastery" is the investigators' secondary outcome. The difference in scores from baseline to 52 weeks is the investigators' outcome measure. The Chronic Respiratory Disease Questionnaire is a valid and reliable questionnaire. 1=minimum score, 7=maximum with the higher score indicating greater mastery. A higher score indicates better health. A change of 0.5 indicates a small change, 1.0 indicates a moderate change and greater or equal to a change of 1.5 indicates a large change.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• /= 40 yrs

• FEV1 </= 70% predicted

• FEV1/FVC <70% predicted

• RV/TLC >/=120%

• SpO2 >/= 90% at peak exercise (with or without exercise)

• inspiratory capacity decline >.15L from rest to peak exercise

Exclusion Criteria:

• respiratory infection/exacerbation within the previous 4 weeks

• exercise limiting heart disease

• primary asthma

• congestive heart failure

• exercise limiting peripheral arterial disease

• stops exercise due to arthritic pain in the knee or hips

• inability to walk on the treadmill

• pregnancy

• methadone use

• any unforeseen illness or disability that would preclude exercise testing or training

• participation in a formal exercise program within the previous 12 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Edward Hines Jr. VA Hospital, Hines, IL	Hines	Illinois	United States	60141-5000

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: Eileen G. Collins, PhD RN, Edward Hines Jr. VA Hospital, Hines, IL

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 13, 2019

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02241733
• Other Study ID Numbers: O1325-R
• First Posted: Sep 16, 2014
• Last Update Posted: Oct 3, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by VA Office of Research and Development: exercise; pulmonary rehabilitation; dynamic hyperinflation

Study Results

Participant Flow

Arm/Group Title	Exercise	Exercise Plus Breathing Retraining
Arm/Group Description	Patients exercised for 12 weeks and then participated in an adherence program Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.	Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.
Period Title: Overall Study
STARTED	40	40
COMPLETED	25	30
NOT COMPLETED	15	10

Baseline Characteristics

Arm/Group Title	Exercise	Exercise Plus Breathing Retraining	Total
Arm/Group Description	Patients will exercise for 12 weeks and then participate in an adherence program Exercise only: Patients will participate in a 12-week exercise program . They will also participate in an adherence program.	Patients will exercise plus breathing retraining for 12 weeks and then participate in an adherence program Breathing retraining plus exercise: Patients will participate in a 12-week exercise program with breathing retraining. They will also participate in an adherence program.	Total of all reporting groups
Overall Participants	40	40	80
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 30%	14 35%	26 32.5%
>=65 years	28 70%	26 65%	54 67.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.5 (6.6)	68.3 (6.6)	67.4 (6.6)
Sex: Female, Male (Count of Participants)
Female	2 5%	1 2.5%	3 3.8%
Male	38 95%	39 97.5%	77 96.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 10%	1 2.5%	5 6.3%
Not Hispanic or Latino	36 90%	39 97.5%	75 93.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	11 27.5%	8 20%	19 23.8%
White	29 72.5%	32 80%	61 76.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	40 100%	40 100%	80 100%
Time walked on constant workload treadmill test (minutes walked) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes walked]	7.2 (1.9)	7.1 (2.0)	7.2 (1.9)
Inspiratory capacity (liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liters]	2.09 (.69)	1.88 (.49)	1.99 (.59)

Outcome Measures

1. Primary Outcome

Title	Duration of Exercise Time on a Constant Work-rate Treadmill Test
Description	Patients walk on a treadmill set at a constant workrate. The difference in the time walked on the treadmill from baseline to study completion is the primary outcome measure.
Time Frame	52 week test

Outcome Measure Data

Analysis Population Description

A multiple imputation model was used to impute missing values for those who did not complete the 52 weeks of the program.

Arm/Group Title	Exercise	Exercise Plus Breathing Retraining
Arm/Group Description	Patients exercised for 12 weeks and then participated in an adherence program Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.	Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.
Measure Participants	40	40
Mean (Standard Deviation) [change in number of minutes walked]	12.2 (3.5)	12.5 (3.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exercise, Exercise Plus Breathing Retraining
	Comments	An independent t-test was completed.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Inspiratory Capacity
Description	Inspiratory capacity is measured at a set time during the constant workrate treadmill test. The difference between the inspiratory capacity measured at baseline and 52 weeks is a secondary outcome. Inspiratory capacity measured during exercise is a measure of dynamic hyperinflation.
Time Frame	52 week test

Outcome Measure Data

Analysis Population Description

A multiple imputation model was used to impute values for those who did not complete the program. The score below is the difference between 52 weeks and baseline.

Arm/Group Title	Exercise	Exercise Plus Breathing Retraining
Arm/Group Description	Patients exercised for 12 weeks and then participated in an adherence program Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.	Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.
Measure Participants	40	40
Mean (Standard Deviation) [difference in liters inspired]	-0.02 (.07)	.15 (.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exercise, Exercise Plus Breathing Retraining
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.078
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	6 Minute Walk Distance
Description	Six-minute walk distance will be measured at 52 weeks. The difference in distance walked in meters between baseline and 52 weeks is the secondary outcome measure. The 6 minute walk is conducted using the guidelines issued by the American Thoracic Society.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Multiple imputation procedures were used to impute data for those that did not complete the protocol

Arm/Group Title	Exercise	Exercise Plus Breathing Retraining
Arm/Group Description	Patients exercised for 12 weeks and then participated in an adherence program Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.	Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.
Measure Participants	40	40
Mean (Standard Deviation) [meters]	25.9 (8.5)	22.8 (8.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exercise, Exercise Plus Breathing Retraining
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Mastery Over Breathing
Description	Mastery over breathing is measured using the Chronic Respiratory Disease Questionnaire. Specifically the subscale 'mastery" is the investigators' secondary outcome. The difference in scores from baseline to 52 weeks is the investigators' outcome measure. The Chronic Respiratory Disease Questionnaire is a valid and reliable questionnaire. 1=minimum score, 7=maximum with the higher score indicating greater mastery. A higher score indicates better health. A change of 0.5 indicates a small change, 1.0 indicates a moderate change and greater or equal to a change of 1.5 indicates a large change.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Multiple imputation was used to impute missing values for those who did not complete the protocol.

Arm/Group Title	Exercise	Exercise Plus Breathing Retraining
Arm/Group Description	Patients exercised for 12 weeks and then participated in an adherence program Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.	Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.
Measure Participants	40	40
Mean (Standard Deviation) [score on a scale]	1.9 (4.9)	2.3 (4.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exercise, Exercise Plus Breathing Retraining
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Adverse event data were collected over the course of study participation (1 year or the time the patients remained in the study).
Arm/Group Title	Exercise		Exercise Plus Breathing Retraining
Arm/Group Description	Patients exercised for 12 weeks and then participated in an adherence program Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.		Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.
All Cause Mortality
	Exercise		Exercise Plus Breathing Retraining
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/40 (2.5%)		2/40 (5%)
Serious Adverse Events
	Exercise		Exercise Plus Breathing Retraining
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/40 (40%)		15/40 (37.5%)
Blood and lymphatic system disorders
cellulitis	0/40 (0%)	0	1/40 (2.5%)	1
leukemia	0/40 (0%)	0	1/40 (2.5%)	1
Cardiac disorders
Atrial fibrillation	1/40 (2.5%)	1	0/40 (0%)	0
Gastrointestinal disorders
Rectal abscess	1/40 (2.5%)	1	0/40 (0%)	0
Nervous system disorders
brain aneurysm	1/40 (2.5%)	1	0/40 (0%)	0
meningioma	0/40 (0%)	0	1/40 (2.5%)	1
Renal and urinary disorders
Kidney stones	1/40 (2.5%)	1	0/40 (0%)	0
Respiratory, thoracic and mediastinal disorders
COPD Exacerbation	13/40 (32.5%)	15	11/40 (27.5%)	11
Vascular disorders
stroke	0/40 (0%)	0	1/40 (2.5%)	1
Other (Not Including Serious) Adverse Events
	Exercise		Exercise Plus Breathing Retraining
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.