Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study has been terminated.
(insufficient enrollment)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ) Identifier:
First received: April 28, 2007
Last updated: June 3, 2013
Last verified: June 2013

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.

Condition Intervention Phase
Hermansky-Pudlak Syndrome (HPS)
Pulmonary Fibrosis
Oculocutaneous Albinism
Platelet Storage Pool Deficiency
Metabolic Disease
Drug: Losartan
Drug: Zileuton
Drug: N-Acetylcysteine
Drug: Pravastatin
Drug: Erythromycin
Phase 1
Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Survival at 2 Years [ Time Frame: 24 months ]
    The number of subjects surviving after 24 months on study.

Enrollment: 3
Study Start Date: April 2007
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Losartan
Losartan potassium tablet, 25 mg by mouth every night at bedtime.
Other Name: Cozaar
Drug: Zileuton
Zileuton tablet, 1200 mg by mouth twice daily.
Other Name: Zyflo
Drug: N-Acetylcysteine
N-acetylcysteine solution, 600 mg by mouth three times daily.
Other Name: acetylcysteine
Drug: Pravastatin
Pravastatin sodium tablet, 20 mg by mouth every night at bedtime.
Other Name: Pravachol
Drug: Erythromycin
Erythromycin tablet, 333 mg by mouth three times daily.
Other Names:
  • E-mycin
  • Ery-tab

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.

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

To be eligible for this protocol, participants must:

  • Have a molecular diagnosis of HPS-1 or HPS-4
  • Be 18-70 years of age
  • Have the expectation to live more than 3 months, i.e., an FVC greater than or equal to 30% of predicted
  • Have evidence of severe pulmonary fibrosis, i.e.:

    1. A FVC less than or equal to 45% of predicted
    2. Reduced exercise tolerance lasting longer than 1 week on the Dyspnea Perception Scale
    3. No evidence of improvement in pulmonary fibrosis within the past year, as defined by an FVC increase of 10% or a DLco increase of 15%.
  • Be available, willing, and able to come to the NIH Clinical Center for admission every 3 months.


  • An explanation for interstitial lung disease other than HPS, including but not limited to radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, cancer
  • Pregnancy or lactation
  • History of ethanol abuse or recreational drug use in the past two years
  • History of human immunodeficiency virus (HIV) or chronic viral hepatitis infection
  • Chronic use of high-dose steroids (greater than 10 mg prednisone/day) intended for ongoing treatment of their interstitial lung disease
  • Use of any of the following within 28 days of enrollment: investigational therapy, cytotoxic/immunosuppressive agents other than corticosteroids, including but not limited to azathioprine, cyclosphosphamide, methotrexate, cyclosporine, colchicine, interferon gamma-1b, bosentan;
  • Any severe medical complication including but not be limited to uncontrolled seizures, repeated transient ischemic attacks, severe ataxia, uncontrolled migraine headaches, diplopia, repeated episodes of syncope, an untreated psychiatric disorder, recent myocardial infarction (past 6 months), unstable angina, clinically relevant and untreated arrhythmias, uncontrolled hypotension or hypertension (systolic blood pressure less than 80 or greater than 180 mm Hg), myocarditis, severe congestive left sided heart failure, hepatomegaly not due to right heart failure, renal glomerular impairment (creatinine clearance less than 35 ml/min/1.73 m(2)), pancreatitis, toxic thyroiditis, life-threatening malignancy;NOTE: right sided heart failure due to pulmonary hypertension as a result of pulmonary fibrosis will not be considered an exclusion criteria.
  • Significant laboratory abnormalities, including but not limited to serum potassium less than 3.0 or greater than 5.4 mEq/L, SGPT greater than 100 U/L, CK greater than 700 U/L, hemoglobin less than 9.0 g/dL, platelets less than 70 k/mm(3), leukocyte count less than 2.0 k/microL;
  • For women of child-bearing age, failure to have an effective method of birth control. Oral contraceptives will be considered inadequate without a second method due to risk of reduced efficacy of BCP while taking Zileuton.
  • Severe psychiatric disease untreated. Inability to give informed consent after reading or having the consent read to the participant in their native language. Any concern that there is a therapeutic misconception will be evaluated by genetic counselor and/or appropriate mental health professionals prior to acceptance into the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00467831

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)
Principal Investigator: Thomas Markello, M.D. National Human Genome Research Institute (NHGRI)
  More Information

Responsible Party: National Human Genome Research Institute (NHGRI) Identifier: NCT00467831     History of Changes
Other Study ID Numbers: 070132
07-HG-0132 ( Other Identifier: NHGRI IRB )
Study First Received: April 28, 2007
Results First Received: June 3, 2013
Last Updated: June 3, 2013

Keywords provided by National Institutes of Health Clinical Center (CC):
Restrictive Lung Disease
Pulmonary Fibrosis
Platelet Storage Pool Deficiency
Metabolic Disease
Hermansky-Pudlak Syndrome
Lung Disease

Additional relevant MeSH terms:
Pulmonary Fibrosis
Metabolic Diseases
Albinism, Oculocutaneous
Hermanski-Pudlak Syndrome
Platelet Storage Pool Deficiency
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Eye Diseases, Hereditary
Eye Diseases
Genetic Diseases, Inborn
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Skin Diseases, Genetic
Pigmentation Disorders
Skin Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Blood Platelet Disorders
Hemorrhagic Disorders
Erythromycin Estolate processed this record on April 24, 2017