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

Idiopathic Pulmonary Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01462006
• Other study ID #: 15282
• Secondary ID: R01HL098329
• Status: Completed
• Phase: N/A
• Start date: October 2011
• Est. completion date: March 2016

Study information

• Verified date: March 2021
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 85 Years

Eligibility

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. 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

16. Inability or unwillingness to comply with the requirements for the trial.

Related Conditions & MeSH terms

• Diffuse Parenchymal Lung Disease
• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Interstitial Lung Disease
• Lung Diseases
• Lung Diseases, Interstitial
• Pulmonary Fibrosis

Intervention

Drug:
• sirolimus
randomized to drug or placebo, followed by washout, followed by crossover

Other:
• Placebo
randomized to drug or placebo, followed by washout, followed by crossover

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Virginia	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	fibrocytes	change in peripheral blood concentration of CXCR4+ fibrocytes	up to 22 weeks
Primary	number of subjects with drug side-effects		up to 22 weeks