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| Descriptive Information Fields | |||||||||
| Brief Title † | Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome | ||||||||
| Official Title † | Therapeutic Clinical Trial of Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome | ||||||||
| Brief Summary | Hermansky-Pudlak Syndrome (HPS) is an inherited disease which results in decreased pigmentation (oculocutaneous albinism), bleeding problems due to a platelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin). The disease can cause poor functioning of the lungs, intestine, kidneys, or heart. The most serious complication of the disease is pulmonary fibrosis and typically causes death in patients ages 40 - 50 years old. The disorder is common in Puerto Rico, where many of the clinical research studies on the disease have been conducted. Neither the full extent of the disease nor the basic cause of the disease is known. There is no known treatment for HPS. The drug Pirfenidone blocks the biochemical process of inflammation and has been reported to slow or reverse pulmonary fibrosis in animal systems. In this study researchers will select 40 patients diagnosed with pulmonary fibrosis 20 who have not received steroid therapy in the last 3 months and 20 currently taking steroids. The patients will be randomly divided into 4 groups. The patients will not know if they are taking pirfenidone or a placebo "sugar pill".
The major outcome measurement of the therapy will be a change in the lung function (forced vital capacity). The study will be stopped if one therapy proves to be more effective than the others. |
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| 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, which is common in Puerto Rico, is pulmonary fibrosis, generally fatal in the fourth or fifth decade. There is no treatment for the pulmonary disease of HPS, which resembles idiopathic pulmonary fibrosis. However, a drug called pirfenidone has antifibrotic effects in animal models of lung fibrosis. Pirfenidone is an IND drug initially provided by Marnac, Inc.; InterMune, Inc., now holds the license. Pirfenidone inhibits cytokine-induced inflammation. Reported side effects include gastrointestinal upset, a photosensitivity rash, and palpitations. Between 1997 and 2001, we performed a randomized, placebo-controlled trial under this protocol that found pirfenidone to be safe and efficacious when analyzed using a repeated measures model. Using a random coefficients model, however, the data were definitive only in the restricted group of subjects whose initial forced vital capacity was greater than 50% of predicted. Vecause the repeated measures analysis had been chosen a priori as the optimal model, the DSMB stopped the study and directed that all patients receive perfenidone. (Of the 23 original patients, ten are alive and 3 are still receiving pirfenidone under this protocol.) However, to prove efficacy of pirfenidone, a new trial must be initiated in which all patients have an initial FVC greater than 50 percent of predicted, and in which the alpha priori method of analysis is the random coefficients model. Hence, the protocol has been amended to include a stratified, block-randomized, placebo-controlled, double-blind trial involing up to 50 HPS patients whose forced vital capacity is 51-85 percent of predicted. For every patient randomly assigned to the placebo group, two will receive pirfenidone. Patients will largely be drawn from the Puerto Rican population and will be previously or simultaneously enrolled in clinical protocol 95-HG-193. They will be admitted to the NIH Clinical Center for 2-3 day admissions every 4 months. The primary efficacy variable will be rate of change in forced vital capacity, determined on every admission and analyzed by the random coefficients method. Secondary efficacy variables will also be examined. A CT scan of the chest, bone density, and arterial blood gases will be performed yearly. |
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| Study Phase | Phase II | ||||||||
| Study Type † | Interventional | ||||||||
| Study Design † | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study | ||||||||
| Primary Outcome Measure † | Change in Forced Vital Capacity [ Time Frame: 3 years; measured every 4 months ] [ Designated as safety issue: No ] | ||||||||
| Secondary Outcome Measure † | Change in other pulmonary function parameters; 6 minute walk [ Time Frame: 3 years; measured every 4 months ] [ Designated as safety issue: No ] | ||||||||
| Condition † | Albinism Inborn Errors of Metabolism Oculocutaneous Albinism Platelet Storage Pool Deficiency Pulmonary Fibrosis |
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| Intervention † | Drug: Pirfenidone (Deskar) Drug: Pirfenidone |
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| MEDLINE PMIDs | 11455388, 9562579, 12126938 | ||||||||
| Links | NIH Clinical Center Detailed Web Page ![]() |
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| Recruitment Information Fields | |||||||||
| Recruitment Status † | Recruiting | ||||||||
| Enrollment † | 73 | ||||||||
| Start Date † | March 1997 | ||||||||
| Completion Date | |||||||||
| Eligibility Criteria † |
For the portion of the protocol involving continuations of pirfenidone treatment, the criteria are simply previous enrollment in 97-HG-0085. For enrollment in the new clinical trial, the inclusion criteria involve enrollment in protocol 95-HG-0193, "Clinical and Basic Investigations into Hermansky-Pudlak Syndrome". This itself requires a diagnosis of HPS based upon molecular grounds or the electron microscopic demonstration of deficiency of platelet dense bodies. In addition, for protocol 97-HG-0085, patients must:
EXCLUSION CRITERIA
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| Gender | Both | ||||||||
| Ages | 18 Years and older | ||||||||
| Accepts Healthy Volunteers | No | ||||||||
| Contacts †† |
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| Location Countries † | United States | ||||||||
| Administrative Information Fields | |||||||||
| NCT ID † | NCT00001596 | ||||||||
| Organization ID | 970085 | ||||||||
| Secondary IDs †† | 97-HG-0085 | ||||||||
| Study Sponsor † | National Human Genome Research Institute (NHGRI) | ||||||||
| Collaborators †† | |||||||||
| Investigators † | |||||||||
| Information Provided By | National Institutes of Health Clinical Center (CC) | ||||||||
| Verification Date | February 2008 | ||||||||
| First Received Date † | November 3, 1999 | ||||||||
| Last Updated Date | September 15, 2008 | ||||||||