Double-blind Placebo-controlled Pilot Study of Sirolimus in Idiopathic Pulmonary Fibrosis (IPF)

Inclusion Criteria:

1. Male and female patients 21-85 years of age

2. Individuals diagnosed with IPF, based on:

   • clinical symptoms consistent with idiopathic pulmonary fibrosis (IPF) of > 3 months duration, plus
   • histologically diagnosed UIP or diagnostic chest high resolution CT features of UIP, plus
   • negative workup for known causes of UIP
3. Ability to understand a written informed consent form and comply with the requirements of the study.

Exclusion Criteria:

1. Clinical features or known diagnosis of an active infection, including untreated latent tuberculosis
2. Clinical features or known diagnosis of malignancy
3. Known diagnosis of an interstitial lung disease other than IPF including but not limited to sarcoidosis, hypersensitivity pneumonitis, non-specific interstitial pneumonia (NSIP).
4. History of clinically significant environmental exposures known to cause interstitial lung disease (including but not limited to drugs, asbestos, silica, beryllium, radiation, domestic birds, etc).
5. Diagnosis of any connective tissue disease (including but not limited to scleroderma, SLE, rheumatoid arthritis) or vasculitides according to the American College of Rheumatology criteria.
6. Systolic blood pressure < 100 or >145 mm Hg or diastolic blood pressure < 50 or >90 mmHg
7. Evidence of active infection within 1 week prior to enrollment.
8. Recently started (<8 weeks prior to baseline visit) or planned cardiopulmonary rehabilitation program before conclusion of the study
9. History of unstable or deteriorating cardiac disease, including but not limited to: myocardial infarction, coronary artery bypass surgery or angioplasty within the past 6 months, congestive heart failure requiring hospitalization within the past 6 months, or uncontrolled arrhythmia
10. History of unstable or deteriorating neurologic disease, including but not limited to: TIAs or stroke
11. Pregnant or lactating females. Females of child bearing potential are required to have a negative serum or urine pregnancy test prior to treatment and agree to practice abstinence or prevent pregnancy by at least a barrier method of birth control.
12. Liver panel above specific limits at screening: Total bilirubin >1.5-fold upper limit of normal, AST, ALT or alkaline phosphatase > 3-fold upper limit of normal at screening.
13. Hematology outside of specified limits, WBC <2,500/ mm3, hematocrit <30, platelets <100,000/mm3 at screening.
14. Investigational therapy for any indication within 28 days prior to treatment.
15. Drugs used for therapy of IPF including azathioprine, colchicine, cyclophosphamide, interferon gamma1b, mycophenolate mofetil, cyclosporin, D-penicillamine, methotrexate, or prednisone at a dose of ≥15mg/day within 28 days prior to enrollment.
16. Current treatment with drugs that are strong inhibitors of CYP3A4 or P-gp, namely bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, HIV-protease inhibitors (e.g., ritonavir, indinavir), metoclopramide, nicardipine, troleandomycin, verapamil
17. Inability or unwillingness to comply with the requirements for the trial.