Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
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.
Hermansky-Pudlak Syndrome (HPS)
Platelet Storage Pool Deficiency
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome|
- Survival at 2 Years [ Time Frame: 24 months ] [ Designated as safety issue: No ]The number of subjects surviving after 24 months on study.
|Study Start Date:||April 2007|
|Study Completion Date:||November 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: Multi-Drug Regimen
Losartan, 25 mg by mouth every night at bedtime; Zileuton, 1200 mg by mouth twice daily; N-acetylcysteine, 600 mg by mouth three times daily; Pravastatin, 20 mg by mouth every night at bedtime; Erythromycin, 333 mg by mouth three times daily.
Losartan potassium tablet, 25 mg by mouth every night at bedtime.
Other Name: CozaarDrug: Zileuton
Zileuton tablet, 1200 mg by mouth twice daily.
Other Name: ZyfloDrug: N-Acetylcysteine
N-acetylcysteine solution, 600 mg by mouth three times daily.
Other Name: acetylcysteineDrug: Pravastatin
Pravastatin sodium tablet, 20 mg by mouth every night at bedtime.
Other Name: PravacholDrug: Erythromycin
Erythromycin tablet, 333 mg by mouth three times daily.
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.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Thomas Markello, M.D.||National Human Genome Research Institute (NHGRI)|