Effect of Sildenafil on Diffusion Capacity in Patients With PH and Parenchymal Lung Disease

September 24, 2014 updated by: Umur Hatipoglu, MD, The Cleveland Clinic

The Effect of Sildenafil on Diffusion Capacity Measurements in Patients With Pulmonary Hypertension and Parenchymal Lung Disease

The purpose of this study was to investigate the acute effects of sildenafil on diffusion capacity, a commonly performed pulmonary function test, which is used to assess the lungs' gas exchange capability.

This study does not assess safety or efficacy of the drug. The study does not have clinical end points. The variables studied are diffusion capacity and 6 minute walk after a single dose of sildenafil.

This study has been completed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Sildenafil is a cyclic GMP selective phosphodiesterase type 5 inhibitor approved for use by the FDA in patients with pulmonary arterial hypertension. There has been recent interest in the use of the drug in patients with diffuse parenchymal lung diseases. This is largely based on sildenafil's salutary effects observed in small studies (Collard et al. 897-99;Ghofrani et al. 895-900;Collard et al. 897-99) and the frequent coexistence of pulmonary hypertension in these patients (Nathan et al. 657-63). In eight patients with pulmonary fibrosis and pulmonary hypertension, sildenafil reduced pulmonary artery pressure and improved shunt fraction as determined by multiple inert gas elimination technique (Ghofrani et al. 895-900;Nathan et al. 657-63). Collard et al demonstrated a 49 meter improvement in 6 minute walk distance in 11 patients with idiopathic pulmonary fibrosis and pulmonary hypertension after 3 months of therapy with sildenafil.

Main theoretical concern with the use of pulmonary arterial vasodilator therapy has been worsening of ventilation perfusion matching due to release of hypoxic vasoconstriction. Such a phenomenon is well recognized during prostacyclin infusion(Ghofrani et al. 895-900;Walmrath et al. 1084-92). Inhaled route seems to circumvent this side effect by preferentially delivering the drug to the alveoli with high V/Q ratios and augmenting blood flow to these regions (Ghofrani et al. 895-900;Walmrath et al. 1084-92). In the only study to address possible effect of systemically administered sildenafil on gas exchange, Ghofrani et al observed improvement in V/Q matching in eight patients using the multiple inert gas elimination technique (MIGET). The authors postulated an enhancement of local defense mechanisms against hypoxia i.e. increased nitric oxide availability to hypoxic alveoli despite oral route of administration(Ghofrani et al. 895-900). In a recent study of 14 normal subjects, oral sildenafil did not effect DLCO measurements at rest, after exercise and under hypoxic conditions(Snyder et al. 421-30).

Diffusion capacity of the lung for carbon monoxide (DLCO) is the clinically available method of assessing gas exchange for practitioners. It is frequently used as a tool for serial monitoring of diffuse parenchymal lung disease. American Thoracic Society has endorsed its use in the assessment of patients with idiopathic interstitial pneumonias(American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias . This Joint Statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS Board of Directors, June 2001 and by The ERS Executive Committee, June 2001 277-304).

The aim of our study was to delineate the effects of orally administered sildenafil on diffusion capacity (absolute value). The significance of this information was twofold. First, it would be helpful clinically to determine the contribution of a pulmonary vasodilator to the change in DLCO to separate this effect from a true clinical change. Second, sildenafil's effect on gas exchange may lead to modifications in therapy such as changes in oxygen flow delivered to patients.

This is not a study that measures clinical outcome or safety of sildenafil. A single dose was administered and effect on diffusion capacity and 6 minute walk were assessed compared to baseline. While we would caution clinicians for rare exceptions to these findings, we believe our data exclude a significant confounding effect in interpretation of diffusion capacity in patients with parenchymal lung disease who are treated for pulmonary hypertension with oral sildenafil. Whether this conclusion holds true at higher doses of sildenafil and in patients with vasodilator response may offer further venues for research.

We were asked to retrospectively register the study at the request of BMC Pulmonary Medicine Journal Editorial Office prior to publication.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult patients over age 18 years of age who are able to consent
  • Diagnosis of diffuse parenchymal lung disease with concomitant pulmonary hypertension

Exclusion Criteria:

  • None

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Oral sildenafil 20 mg
oral sildenafil, single dose at baseline
Drug: Oral sildenafil 20 mg
A single dose of sildenafil will be given after recording baseline diffusion capacity and 6 minute walk. Measurements will be repeated one hour after the drug.
Other Names:
  • sildenafil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Diffusion Capacity Measured at Baseline and One Hour.
Time Frame: Baseline and one hour
Determine the acute effect of oral sildenafil on diffusion capacity in patients with diffuse parenchymal lung disease and concomitant pulmonary hypertension
Baseline and one hour

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in 6 Minute Walk Distance
Time Frame: Baseline and one hour
The change in 6 minutes walk distance from baseline one hour after receiving 20 mg of sildenafil orally will be measured.
Baseline and one hour

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Cleveland Clinic

Investigators

  • Principal Investigator: Umur Hatipoglu, MD, The Cleveland Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (ACTUAL)

June 1, 2012

Study Completion (ACTUAL)

June 1, 2012

Study Registration Dates

First Submitted

September 18, 2013

First Submitted That Met QC Criteria

September 19, 2013

First Posted (ESTIMATE)

September 23, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

September 30, 2014

Last Update Submitted That Met QC Criteria

September 24, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-993

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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