Rehabilitation of Idiopathic Pulmonary Fibrosis (IPF) Patients

• Sponsor: US Department of Veterans Affairs (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01118221
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The incidence and prevalence of IPF increase exponentially with age, and IPF occurs more often in older males. Cigarette smoking and environmental dust exposures are known risk factors for developing IPF. For example, the recently deployed military population, as it ages, is at especially increased risk of IPF. No effective therapies exist, although lung transplantation is used to extend survival of selected patients.

Defining specific therapy to improve exercise tolerance and dyspnea in IPF patients is thus an urgent priority of veteran-oriented research programs.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis	Behavioral: pulmonary rehabilitation	N/A

Detailed Description

Chronic lung disease is common in the veteran population. While chronic obstructive pulmonary disease (COPD) is most prominent, fibrotic lung diseases, typified by idiopathic pulmonary fibrosis (IPF), are clearly increasing. We have developed extensive experience with a VA idiopathic pulmonary fibrosis (IPF) population in the context of a randomized, controlled clinical trial of vasodilator therapy.

Based on the current literature and our preliminary experience with exercise testing in IPF patients, we hypothesize that:

1. Formal pulmonary rehabilitation (i.e., an aerobic exercise program) will result in improved outcomes for IPF patients, demonstrable as an:

2. Increase in exercise tolerance as quantified by 6-minute walk test (MWT) distance;

3. Decrease in post-exercise dyspnea as quantified by the Borg dyspnea scale; and an

4. Overall subjective improvement in quality of life as quantified by Saint George's Respiratory Questionnaire.

5. Metabolic and physiologic mechanisms of improved exercise tolerance and decreased dyspnea will include:

6. More efficient oxygen metabolism demonstrated by maximum O2 uptake (VO2max);

7. Decreased post-exercise oxidant stress demonstrated by post-exercise isoprostanes and plasma total antioxidant capacity (TAC); and,

8. Maintenance of maximum inspiratory and expiratory pressures (PInmax and PExmax).

Our Specific Objectives are:

1. To investigate formal pulmonary rehabilitation and exercise tolerance in IPF patients

The following important endpoints will be assessed to test the working hypothesis that pulmonary rehabilitation improves exercise capacity and lessens dyspnea:

1. 6-MWT distance;

2. Dyspnea index; and,

3. Quality of life (Saint George's Respiratory Questionnaire [SGRQ] and International Physical Activity Questionnaire [IPAQ]).

4. To assess changes in oxygen uptake, markers of oxidant stress and pulmonary function resulting from pulmonary rehabilitation

To test the working hypothesis that improved outcomes are associated with more efficient O2 utilization, decreased markers of oxidant stress and maintained effort dependent pulmonary function, the following variables will be measured:

1. Peak oxygen uptake (VO2peak) during constant load exercise;

2. Markers of oxidant stress, including plasma and urine isoprostanes; and,

3. Maximum inspiratory and expiratory pressures (PInmax and PExmax). Completion of these Specific Objectives will position our research group to conduct future studies of 1) mechanisms of exercise limitation and 2) antioxidant therapies, both in this defined population and those who are at risk of developing pulmonary fibrosis. The long term impact of this application is thus to develop effective pulmonary rehabilitation strategies for IPF patients, based on knowledge of underlying changes in oxygen metabolism and oxidant stress.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Rehabilitation of IPF Patients: Effects of Exercise and Oxidant Stress
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 enroll in pulmonary rehabilitation program	Behavioral: pulmonary rehabilitation; structured exercise program
No Intervention: Arm 2 no structured exercise

Outcome Measures

Primary Outcome Measures

1. 6 Minute Walk Distance [The 6-MWD will be measured at 0 and 3 months.]

   Change in 6 Minute Walk Distance from Baseline to 3 Months

Secondary Outcome Measures

1. Systemic Markers of Oxidant Stress [Markers of oxidant stress will be measured in all subjects before randomization after exercise testing at 0 months.]

   Plasma F2-isoprostanes measured in all subjects before and after exercise testing at baseline.

2. Maximum Oxygen Uptake [Maximum O2 uptake will be measured at 0 and 3 months.]

   Change in 6 peak O2 uptake from Baseline to 3 Months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical presentation consistent with IPF with onset between three months and 48 months prior to screening.

• Diagnosis made by high-resolution computed tomographic scan showing highly probable IPF.

• Absence of severe pulmonary hypertension (i.e., PAsys must be less than 55 mm Hg, based on echocardiography) and absence of decompensated right heart failure (NYHA class I or II acceptable).

• Age 40 through 80, inclusive.

• Abnormal pulmonary function tests (FVC 40-90% predicted or DLCO 30-90% predicted or impaired gas exchange with rest or exercise).

• Six-minute walk distance 150 m and 500 m.

• Worsening as demonstrated by any one of the following within the past year: > 10% decrease in percent predicted forced vital capacity or worsening dyspnea at rest or upon exertion, based on history.

• Ability to understand and sign a written informed consent form and comply with the requirements of the study.

• Absence of clinical features suggesting infection, neoplasm, sarcoidosis or collagen-vascular disease.

Exclusion Criteria:

• Echocardiographic evidence of severe pulmonary hypertension (PAsys>55 mm Hg, based on echocardiography or TR velocity 3.2 m/sec).

• Severe heart failure (NYHA class III or IV or LVEF < 45%).

• Six-minute walk distance < 150 m or > 500 m.

• FEV1/FVC ratio < 0.7 at screening (post-bronchodilator).

• Residual volume > 100% predicted.

• Any condition other than IPF likely to result in the death of the participant within the next two years.

• History of unstable or deteriorating cardiac or neurologic disease.

• Pregnancy or lactation. Patients who are: (a) pregnant or (b) breast feeding are excluded from the study.

• Current treatment with corticosteroids (either oral or inhaled), Cytoxan, azathioprine, colchicine, pirfenidone, anti-tumor necrosis factor therapy or endothelin receptor blockers. Prior treatment is permitted, but at least four weeks of treatment washout prior to inclusion in this study are required.

• Investigational therapy for any indication within 28 days prior to enrollment.

• Degenerative arthritis, cerebrovascular accident or other limitation to mobility preventing completion of the 6-minute walk test.

• Oxygen saturation on room air <80% at rest.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Medical Center, Miami	Miami	Florida	United States	33125

Sponsors and Collaborators

• US Department of Veterans Affairs

Investigators

• Principal Investigator: Robert M Jackson, MD, VA Medical Center, Miami

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: US Department of Veterans Affairs
• ClinicalTrials.gov Identifier: NCT01118221
• Other Study ID Numbers: O7467-R
• First Posted: May 6, 2010
• Last Update Posted: Mar 4, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by US Department of Veterans Affairs: oxidant stress; exercise
• Additional relevant MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis

Study Results

Participant Flow

Arm/Group Title	Pulmonary Rehabilitation	Control
Arm/Group Description	enroll in pulmonary rehabilitation program pulmonary rehabilitation: structured exercise program	no structured exercise
Period Title: Overall Study
STARTED	14	11
COMPLETED	11	10
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Pulmonary Rehabilitation	Control	Total
Arm/Group Description	enroll in pulmonary rehabilitation program pulmonary rehabilitation: structured exercise program	no structured exercise	Total of all reporting groups
Overall Participants	14	11	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71 (6)	66 (7)	69 (6)
Sex: Female, Male (Count of Participants)
Female	2 14.3%	2 18.2%	4 16%
Male	12 85.7%	9 81.8%	21 84%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 42.9%	6 54.5%	12 48%
Not Hispanic or Latino	8 57.1%	5 45.5%	13 52%
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	1 7.1%	0 0%	1 4%
White	13 92.9%	11 100%	24 96%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	14 100%	10 90.9%	24 96%
South America	0 0%	1 9.1%	1 4%

Outcome Measures

1. Primary Outcome

Title	6 Minute Walk Distance
Description	Change in 6 Minute Walk Distance from Baseline to 3 Months
Time Frame	The 6-MWD will be measured at 0 and 3 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	enroll in pulmonary rehabilitation program pulmonary rehabilitation: structured exercise program	no structured exercise
Measure Participants	14	11
Mean (Standard Deviation) [meters]	-6.2 (86.9)	-15.3 (42.9)

2. Secondary Outcome

Title	Systemic Markers of Oxidant Stress
Description	Plasma F2-isoprostanes measured in all subjects before and after exercise testing at baseline.
Time Frame	Markers of oxidant stress will be measured in all subjects before randomization after exercise testing at 0 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Before Exercise Testing	After Exercise Testing
Arm/Group Description	Plasma isoprostanes before exercise test.	Plasma isoprostanes after exercise testing.
Measure Participants	25	25
Mean (Standard Deviation) [pg/mL]	16.48 (10.10)	17.96 (10.05)

3. Secondary Outcome

Title	Maximum Oxygen Uptake
Description	Change in 6 peak O2 uptake from Baseline to 3 Months
Time Frame	Maximum O2 uptake will be measured at 0 and 3 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rehabilitation Group	Control Group
Arm/Group Description	enroll in pulmonary rehabilitation program pulmonary rehabilitation: structured exercise program	no structured exercise
Measure Participants	14	11
Mean (Standard Error) [mL/minute]	-35 (71)	-119 (62)

Adverse Events

Time Frame	Six months.
Adverse Event Reporting Description	Adverse and unexpected events were recorded.
Arm/Group Title	Arm 1		Arm 2
Arm/Group Description	enroll in pulmonary rehabilitation program pulmonary rehabilitation: structured exercise program		no structured exercise
All Cause Mortality
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/11 (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.