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| Tracking Information | |||||||||
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| First Received Date ICMJE | November 3, 1999 | ||||||||
| Last Updated Date | November 17, 2009 | ||||||||
| Start Date ICMJE | March 1997 | ||||||||
| Estimated Primary Completion Date | December 2012 (final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
Change in Forced Vital Capacity [ Time Frame: 3 years; measured every 4 months ] [ Designated as safety issue: No ] | ||||||||
| Original Primary Outcome Measures ICMJE |
Change in Forced Vital Capacity | ||||||||
| Change History | Complete list of historical versions of study NCT00001596 on ClinicalTrials.gov Archive Site | ||||||||
| Current Secondary Outcome Measures ICMJE |
Change in other pulmonary function parameters; 6 minute walk [ Time Frame: 3 years; measured every 4 months ] [ Designated as safety issue: No ] | ||||||||
| Original Secondary Outcome Measures ICMJE |
Change in other pulmonary function parameters; 6 minute walk | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome | ||||||||
| Official Title ICMJE | 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. Because the repeated measures analysis had been chosen a priori as the optimal model, the DSMB stopped the study and directed that all patients receive pirfenidone. (Of the 23 original patients, 3 are still receiving pirfenidone under this protocol.) Now, to prove efficacy of pirfenidone, we are conducting a stratified, block-randomized, placebo-controlled, double-blind trial involving up to 50 HPS patients whose forced vital capacity is 51-85% of predicted. For every patient randomly assigned to the placebo group, two will receive pirfenidone. Patients are largely drawn from the Puerto Rican population and are simultaneously enrolled in clinical protocol 95-HG-193. They are admitted to the NIH Clinical Center for 2-3 day admissions every 4 months. The primary efficacy variable is rate of change in forced vital capacity, determined on every admission and analyzed by the random coefficients method. Secondary efficacy variables are also examined. A CT scan of the chest, bone density, and arterial blood gases are performed yearly. After 4 years of patient accrual, 35 patients were enrolled; the original statistical analysis plan (SAP) called for 39 patients to be enrolled within one year. The NHGRI DSMB revised the original SAP to perform an interim data analysis 12 months after 30 patients were enrolled, i.e., in May of 2009. That analysis directed the study to stop due to futility. However, this protocol will continue to provide pirfenidone to the three original protocol patients still enrolled, and to any pirfenidone-treated patients who choose to undergo pulmonary lavage to help us determine the effects of pirfenidone on the cytokine profile of alveolar macrophages. The lavages would require enrollment in protocol. The treatment drug will be stopped immediately for all placebo patients and for pirfenidone patients who do not plan to enroll in the lavage protocol. Pirfenidone treatment will stop just after the lavage is performed on patients who do enroll in the lavage protocol, 04-HG-0211. All patients will be invited to continue to come to the NIH annually under the HPS natural history protocol, 95-HG-0193. |
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| Study Phase | Phase II | ||||||||
| Study Type ICMJE | Interventional | ||||||||
| Study Design ICMJE | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study | ||||||||
| Condition ICMJE |
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| Intervention ICMJE |
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| Study Arms / Comparison Groups | |||||||||
| Publications * |
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* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Enrollment ICMJE | 73 | ||||||||
| Estimated Completion Date | December 2012 | ||||||||
| Estimated Primary Completion Date | December 2012 (final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE |
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 ICMJE |
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| Location Countries ICMJE | United States | ||||||||
| Administrative Information | |||||||||
| NCT ID ICMJE | NCT00001596 | ||||||||
| Responsible Party | William A. Gahl, M.D./National Human Genome Research Institute, National Institutes of Health | ||||||||
| Study ID Numbers ICMJE | 970085, 97-HG-0085 | ||||||||
| Study Sponsor ICMJE | National Human Genome Research Institute (NHGRI) | ||||||||
| Collaborators ICMJE | |||||||||
| Investigators ICMJE | |||||||||
| Information Provided By | National Institutes of Health Clinical Center (CC) | ||||||||
| Verification Date | January 2009 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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