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

Sponsor

University of Virginia (Other)

Overall Status

Completed

CT.gov ID

NCT01462006

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arms

Actual Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Idiopathic pulmonary fibrosis (IPF) is an illness characterized by progressive decline in lung function and premature death from respiratory failure. Fibrocytes are a novel population of bone marrow-derived circulating progenitor cells that have been shown to traffic to the lungs and contribute to fibrosis in animal models of pulmonary fibrosis, and whose numbers correlate with the degree of fibrosis and with survival in human pulmonary fibrosis. The investigators propose to test the hypothesis that therapy with the mTOR inhibitor, sirolimus, reduces the number of circulating fibrocytes in patients with IPF. The investigators propose to test this hypothesis in short-term pilot trial of sirolimus in patients with IPF to determine its effect on the number and phenotype of circulating fibrocytes.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis Diffuse Parenchymal Lung Disease Interstitial Lung Disease	Drug: sirolimus Other: Placebo	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Double-blind Placebo-controlled Pilot Study of Sirolimus in IPF

Actual Study Start Date :

Oct 1, 2011

Actual Primary Completion Date :

Mar 1, 2016

Actual Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sirolimus	Drug: sirolimus randomized to drug or placebo, followed by washout, followed by crossover
Placebo Comparator: Placebo	Other: Placebo randomized to drug or placebo, followed by washout, followed by crossover

Arm

Intervention/Treatment

Experimental: Sirolimus

Drug: sirolimus

randomized to drug or placebo, followed by washout, followed by crossover

Placebo Comparator: Placebo

Other: Placebo

randomized to drug or placebo, followed by washout, followed by crossover

Outcome Measures

Primary Outcome Measures

fibrocytes [up to 22 weeks]
change in peripheral blood concentration of CXCR4+ fibrocytes
number of subjects with drug side-effects [up to 22 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female patients 21-85 years of age
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

Ability to understand a written informed consent form and comply with the requirements of the study.

Exclusion Criteria:

Clinical features or known diagnosis of an active infection, including untreated latent tuberculosis
Clinical features or known diagnosis of malignancy
Known diagnosis of an interstitial lung disease other than IPF including but not limited to sarcoidosis, hypersensitivity pneumonitis, non-specific interstitial pneumonia (NSIP).
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).
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.
Systolic blood pressure < 100 or >145 mm Hg or diastolic blood pressure < 50 or >90 mmHg
Evidence of active infection within 1 week prior to enrollment.
Recently started (<8 weeks prior to baseline visit) or planned cardiopulmonary rehabilitation program before conclusion of the study
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
History of unstable or deteriorating neurologic disease, including but not limited to: TIAs or stroke
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.
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.
Hematology outside of specified limits, WBC <2,500/ mm3, hematocrit <30, platelets <100,000/mm3 at screening.
Investigational therapy for any indication within 28 days prior to treatment.
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
Inability or unwillingness to comply with the requirements for the trial.