Trials / Terminated

TerminatedNCT00467831

Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome

Status: Terminated
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 3 (actual)

Sponsor: National Human Genome Research Institute (NHGRI) · NIH
Sex: All
Age: 18 Years – 70 Years
Healthy volunteers: Not accepted

Summary

This study will examine whether five drugs (pravastatin, Losartan, Zileuton, N-acetylcysteine and erythromycin) used together can slow the course of pulmonary fibrosis (scarring of the lung tissue) in patients with Hermansky-Pudlak Syndrome (HPS). Patients with this disease have decreased skin color (albinism), bleeding problems, and sometimes colon problems. Two of the known types of Hermansky Pudlak syndrome, type 1 and type 4, are at high risk of pulmonary fibrosis between the ages of 30 and 50. Patients 18 to 70 years of age who have Hermansky-Pudlak Syndrome with a serious loss of lung function due to pulmonary fibrosis may be eligible for this study. Participants begin taking pravastatin on study day 2 and start a new drug every 3 days. Patients who experience no problems with the medicines return home and continue on the drugs for the next 2 years. They return to the NIH Clinical Center every 3 months for a medical history, physical examination, and blood, urine and lung function tests. CT and bone density scans are done every year. The study may continue for up to 3 years.

Detailed description

Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive disease consisting of oculocutaneous albinism and a platelet storage pool defect. The most serious complication of this disorder, pulmonary fibrosis, occurs only in genetic subtypes HPS-1 and HPS-4 and is generally fatal in the fourth or fifth decade. HPS-1 is very common in northwest Puerto Rico. There is no effective treatment for the pulmonary disease of HPS (HPS-PF), which resembles idiopathic pulmonary fibrosis (IPF). A preliminary study of the antifibrotic drug, pirfenidone, gave promising results for mild to moderate HPS-PF, but not for severe pulmonary fibrosis. A second study is currently addressing only mild to moderate HPS-PF. Other drugs, studied in IPF as single agents, have some efficacy for mild to moderate disease, but none has had a major effect on mortality. Recently, a call has been made for consideration of multi-drug therapy (i.e., an oncologic approach) for severe pulmonary fibrosis. Based upon positive responses from companies producing relevant drugs, we propose a multi-drug trial using five agents: Losartan, Zileuton, a generic statin (Pravastatin), generic N-acetylcysteine, and generic Erythromycin. Participants with severe pulmonary fibrosis will be drawn largely from the Puerto Rican population. Eligibility will require a molecular diagnosis of HPS-1 or HPS-4, radiographic evidence of interstitial lung disease, persistent pulmonary function testing less than or equal to 45% of predicted after bronchodilation, and absence of other causes of lung dysfunction. Participants will be admitted to the NIH Clinical Center for a 21-day admission to establish baseline function and to begin medication therapy. Follow-up admissions (3 days) will occur every 3 months. The primary outcome parameter will be survival at 2 years.

Conditions

Interventions

Type	Name	Description
DRUG	Losartan	Losartan potassium tablet, 25 mg by mouth every night at bedtime.
DRUG	Zileuton	Zileuton tablet, 1200 mg by mouth twice daily.
DRUG	N-Acetylcysteine	N-acetylcysteine solution, 600 mg by mouth three times daily.
DRUG	Pravastatin	Pravastatin sodium tablet, 20 mg by mouth every night at bedtime.
DRUG	Erythromycin	Erythromycin tablet, 333 mg by mouth three times daily.

Timeline

Start date: 2007-04-01
Primary completion: 2012-11-01
Completion: 2012-11-01
First posted: 2007-05-01
Last updated: 2013-08-02
Results posted: 2013-08-02

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT00467831. Inclusion in this directory is not an endorsement.