Targeting Vascular Reactivity in Idiopathic Pulmonary Fibrosis
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|ClinicalTrials.gov Identifier: NCT00981747|
Recruitment Status : Terminated (Funding was withdrawn.)
First Posted : September 22, 2009
Results First Posted : November 12, 2018
Last Update Posted : November 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|Idiopathic Pulmonary Fibrosis Pulmonary Fibrosis||Drug: Sildenafil Drug: Losartan Drug: Sildenafil and Losartan Drug: Placebo Oral Tablet||Phase 2 Phase 3|
It is currently suspected that the fibrosis in IPF is based upon an abnormal reparative process in the lung. Normally, an insult to the endothelium or epithelium of the lung would trigger an inflammatory process to help repair the site of injury; epithelial and endothelial cells then replicate and repair the tissue damage. In pulmonary fibrosis, alterations in this cascade change the balance of the inflammatory products and reduce the regulatory response which can produce continued inflammation. Fibrosis results from continued deposition of collagen by proliferating fibroblasts and lack of collagen breakdown.
In addition to fibrosis and microvascular destruction, pulmonary hypertension in IPF patients is a significant contributor to morbidity and mortality. The prevalence ranges from 32-85%, suggesting that pulmonary vascular disease is one of several processes that contribute to severity of disease.
We propose use of two therapeutic agents that affect the balance of vasoconstriction and vasodilation to improve basal tone of the vasculature. First, we propose the use of a phosphodiesterase inhibitor. Sildenafil (Viagra, Revatio) is an orally administered vasodilator that prolongs the effect of nitric oxide by inhibiting phosphodiesterase type 5 (PDE-5) which is responsible for degradation of cGMP. Increased cGMP concentration results in pulmonary vasculature relaxation and consequent vasodilation. Second, the use of an angiotensin receptor blocker (ARB) acts to diminish the direct vasoconstrictor effect of angiotensin and endothelin-1 in the vessels. In treatment of systemic hypertension, ARBs have been shown to be associated with a decrease in the amount of circulating endothelin-1 and increase in basal nitric oxide release. They have also been shown to rapidly inhibit the generation of reactive oxygen species by inflammatory cells. We test these interventions in a randomized cross-over trial in IPF patients.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Participants will receive sildenafil for three months then losartan for three months, then sildenafil and losartan for three months and then placebo for three months in a random order.|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Clinical Treatment Trial Targeting Vascular Reactivity in Idiopathic Pulmonary Fibrosis|
|Actual Study Start Date :||September 2009|
|Actual Primary Completion Date :||December 2016|
|Actual Study Completion Date :||December 2016|
Experimental: All study participants
Study participants are patients that have been diagnosed with idiopathic pulmonary fibrosis (IPF).
Sildenafil 20mg three times per day for 3 months followed by a one month washout prior to next intervention.
Losartan 25mg two times a day for 3 months followed by a one month washout prior to next intervention.
Other Name: Cozaar: losartan
Drug: Sildenafil and Losartan
Sildenafil 20mg three times per day and Losartan 25mg two times per day followed by a one month washout prior to next intervention.
Drug: Placebo Oral Tablet
Placebo pill three times per day for 3 months followed by a one month washout prior to next intervention.
Other Name: Placebo pill (sugar)
- Change in Six Minute Walk Distance in Meters [ Time Frame: At baseline and three months post each intervention. ]Change in 6MWD before and after treatment compared to placebo
- Change in Forced Vital Capacity (FVC) [ Time Frame: At baseline and three months post each intervention. ]Change in FVC before and after treatment compared to placebo. FVC is a measure of lung size.
- Change in Shortness of Breath (SOB) Score [ Time Frame: At baseline and three months post each intervention. ]Change in symptoms of SOB as determined by St. Georges Respiratory Questionnaire score. This score ranges from 0 to 100 with a higher score indicating more problems breathing.
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): NCT00981747
|United States, Iowa|
|University of Iowa Hospitals and Clinics|
|Iowa City, Iowa, United States, 52246|
|Principal Investigator:||Alicia K Gerke, MD||University of Iowa|