Rehabilitation of Idiopathic Pulmonary Fibrosis (IPF) Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01118221
First received: April 27, 2010
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

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 Intervention
Idiopathic Pulmonary Fibrosis
Behavioral: pulmonary rehabilitation

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rehabilitation of IPF Patients: Effects of Exercise and Oxidant Stress

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • 6 minute walk distance [ Time Frame: The 6-MWD will be measured at 0, 3 and 6 months. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • systemic markers of oxidant stress [ Time Frame: Markers of oxidant stress will be measured at 0, 3 and 6 months. ] [ Designated as safety issue: No ]
  • maximum oxygen uptake [ Time Frame: Maximum O2 uptake will be measured at 0, 3 and 6 months. ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: October 2010
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
enroll in pulmonary rehabilitation program
Behavioral: pulmonary rehabilitation
structured exercise program
No Intervention: Arm 2
no structured exercise

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:

    1. Increase in exercise tolerance as quantified by 6-minute walk test (MWT) distance;
    2. Decrease in post-exercise dyspnea as quantified by the Borg dyspnea scale; and an
    3. Overall subjective improvement in quality of life as quantified by Saint George's Respiratory Questionnaire.
  2. Metabolic and physiologic mechanisms of improved exercise tolerance and decreased dyspnea will include:

    1. More efficient oxygen metabolism demonstrated by maximum O2 uptake (VO2max);
    2. Decreased post-exercise oxidant stress demonstrated by post-exercise isoprostanes and plasma total antioxidant capacity (TAC); and,
    3. 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]).
  2. 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. Maximum oxygen uptake (VO2max);
  2. Markers of oxidant stress, including plasma and urine isoprostanes and plasma total antioxidant capacity; 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.
  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 50 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>50 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 N-acetylcysteine or other antioxidant, 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01118221

Locations
United States, Florida
VA Medical Center, Miami
Miami, Florida, United States, 33125
Sponsors and Collaborators
Investigators
Principal Investigator: Robert M Jackson, MD VA Medical Center, Miami
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01118221     History of Changes
Other Study ID Numbers: O7467-R
Study First Received: April 27, 2010
Last Updated: November 20, 2013
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
oxidant stress
exercise

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial

ClinicalTrials.gov processed this record on July 24, 2014