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

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

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis; Interstitial Lung Disease; Diffuse Parenchymal Lung Disease
• Intervention / Treatment: Drug: sirolimus; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fibrocytes	change in peripheral blood concentration of CXCR4+ fibrocytes	up to 22 weeks
number of subjects with drug side-effects		up to 22 weeks

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Borna Mehrad, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2011
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: October 26, 2011
• First Submitted That Met QC Criteria: October 27, 2011
• First Posted (Estimate): October 28, 2011

Study Record Updates

• Last Update Posted (Actual): March 22, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Fibrosis; Lung Diseases; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 15282; R01HL098329 (U.S. NIH Grant/Contract)