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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Virginia
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Virginia
ClinicalTrials.gov Identifier:
NCT01462006
First received: October 26, 2011
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

Idiopathic pulmonary fibrosis (IPF) is an illness characterized by progressive decline in lung function and premature death from respiratory failure. There is currently no effective therapy for this disease. 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 Intervention
Idiopathic Pulmonary Fibrosis
Diffuse Parenchymal Lung Disease
Interstitial Lung Disease
Drug: sirolimus
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-blind Placebo-controlled Pilot Study of Sirolimus in IPF

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • fibrocytes [ Time Frame: up to 22 weeks ] [ Designated as safety issue: No ]
    change in peripheral blood concentration of CXCR4+ fibrocytes

  • number of subjects with drug side-effects [ Time Frame: up to 22 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 45
Study Start Date: October 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   21 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01462006

Contacts
Contact: Hong Zhu, RN 434-243-7364 hz3d@virginia.edu
Contact: Borna Mehrad, MD 434-243-4845 Mehrad@virginia.edu

Locations
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Borna Mehrad, MD University of Virginia
  More Information

No publications provided

Responsible Party: University of Virginia
ClinicalTrials.gov Identifier: NCT01462006     History of Changes
Other Study ID Numbers: 15282, R01HL098329
Study First Received: October 26, 2011
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Fibrosis
Lung Diseases
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Lung Diseases, Interstitial
Idiopathic Interstitial Pneumonias
Pathologic Processes
Respiratory Tract Diseases
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014