NCT00981747

Targeting Vascular Reactivity in Idiopathic Pulmonary Fibrosis

A Clinical Treatment Trial Targeting Vascular Reactivity in Idiopathic Pulmonary Fibrosis

• Status: Terminated
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Alicia Gerke · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether combination therapy with sildenafil and losartan can improve function and exercise tolerance in patients with idiopathic pulmonary fibrosis.

Detailed description

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.

Conditions

• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Interventions

Type	Name	Description
DRUG	Sildenafil	Sildenafil 20mg three times per day for 3 months followed by a one month washout prior to next intervention.
DRUG	Losartan	Losartan 25mg two times a day for 3 months followed by a one month washout prior to next intervention.
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.

Timeline

• Start date: 2009-09-01
• Primary completion: 2016-12-01
• Completion: 2016-12-01
• First posted: 2009-09-22
• Last updated: 2018-11-13
• Results posted: 2018-11-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study