Clinical trial: Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome (NCT00001596)

Eligibility criteria:
-  INCLUSION 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:

          -  Be over 18 years of age.

          -  Have an FVC greater than 50 percent and less than or equal to 85 percent of predicted
             OR a hemoglobin-corrected DL(co) greater than 35 percent and less than or equal to 80
             percent of predicted, with no evidence of a pulmonary embolism.

          -  Have evidence of reduced exercise tolerance lasting longer than one week on either the
             St. George's Hospital Respiratory Questionnaire or the Dyspnea Perception Scale.

          -  FEV(1)/FVC greater than 80 percent of predicted after bronchodilators.

          -  No evidence of improvement in pulmonary fibrosis within the past year defined as an
             FVC increased by 10 percent or a DL(co) increased by 15 percent.

          -  Distance walked greater than or equal to 150 meters (492 feet) with oxygen saturation
             greater than or equal to 83 percent on less than or equal to 6 L/min. of oxygen during
             the 6-Minute Walk Test (6MWT).

          -  Be available, willing, and able to come to the NIH Clinical Center for admission every
             4 months for three years.

        EXCLUSION CRITERIA

          -  History of clinically significant environmental exposure known to cause pulmonary
             fibrosis (including but not limited to drugs, asbestos, beryllium, radiation, domestic
             birds).

          -  An explanation for interstitial lung disease other than HPS, including but not limited
             to radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans
             organizing pneumonia, cancer.

          -  Diagnosis of any connective tissue disease including but not limited to scleroderma,
             systemic lupus erythematosus, rheumatoid arthritis.

          -  Listing on a lung transplantation waiting list.

          -  Pregnancy or lactation

          -  Cigarette smoking in the past 6 months

          -  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)

          -  Prior use of pirfenidone

          -  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); cytokine
             modulators (including but not limited to etanercept and infliximab); therapies
             targeted to treat pulmonary fibrosis (including but not limited to D-penicillamine,
             colchicine, interferon gamma-1b, bosentan, N-acetylcysteine

          -  Any severe medical complication including but not be limited to uncontrolled seizures,
             repeated transient ischemic attacks, abnormal mental status, severe ataxia,
             uncontrolled migraine headaches, diplopia, repeated episodes of syncope, untreated
             clinical depression, recent myocardial infarction (past 6 months), unstable angina,
             clinically relevant arrhythmias, uncontrolled hypotension or hypertension (systolic
             blood pressure less than 80 or greater than 180 mm Hg), myocarditis, hepatomegaly
             (liver greater than 3 cm below the right costal margin), renal glomerular impairment
             (creatinine clearance less than 35 ml/min/1.73 m2, pancreatitis, toxic thyroiditis,
             malignancy (except basal cell carcinoma)

          -  Medications with a high frequency of life threatening side effects

          -  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/mm3, leucocyte count
             less than 2.0 k/microliter, or cholesterol greater than 400 mg/dL.

          -  For women of child bearing age, failure to have an effective method of birth control.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 4-year-old boy comes to the office for the follow up of his confirmed oculocutaneous albinism.  The patient was born at 38 weeks gestation with no complications.  Vital signs are normal.  Weight and height are at the 50th percentile.  On examination, iris transillumination is present, and there are no apparent foveae on funduscopic examination.  Optic nerves are small and gray.  All the hairs including eyebrows and lashes are white.

Patient description (patient's own words): I brought my four-year-old son to his follow-up consultation for his albinism. All his hair is white, even lashes and eyebrows. My baby was born at 38 weeks pregnant with no complications whatsoever. During the consultations his vitals were normal and now his weight and height are at the 50th percentile. The doctor did an eye exam and it seems that his iris has a kind of transillumination, and there are no foveae. The doctor told me that his optic nerves are small and gray.

Does the patient match the trial criteria? 0