Atorvastatin to Treat Pulmonary Sarcoidosis
This study will determine if atorvastatin (Lipitor), a widely used cholesterol-lowering drug, can help patients with pulmonary (lung) sarcoidosis and replace or reduce the need for patients to take steroids, such as prednisone. Sarcoidosis is an inflammatory disease that can affect nearly any part of the body. Pulmonary sarcoidosis may resolve on its own or it may progress to irreversible lung damage, disability, and death. Many sarcoidosis patients are treated with prednisone, but the drug is not effective in all patients, and it can cause serious side effects, such as high blood pressure, sugar diabetes, eye cataracts, and bone thinning.
Patients with stage II or III pulmonary sarcoidosis between 18 and 70 years of age who require prednisone may be eligible for this study. Candidates are screened with the tests and procedures described below.
Participants are randomly assigned to one of two treatment groups: one group takes atorvastatin; the other takes a placebo (a look-alike pill that has no active ingredient to fight sarcoidosis). Both groups take the pills by mouth once a day for 12 months. When treatment begins, participants begin to have their prednisone dosage tapered (reduced). The tapering is done over 8 weeks until the dose is reduced by 90 percent. Patients are evaluated periodically to determine if the two groups differ in how long they can remain on the reduced dose of prednisone without having their symptoms recur, requiring an increase in the prednisone dose. A full battery of tests is done at the initial screening visit and at the 26- and 52-week follow-up visits, requiring hospitalization for 3-5 days. Additional interim outpatient assessments are done at 6, 12, 18 and 36 weeks.
The full battery of tests at the initial screening and the 26- and 52-week visits includes the following:
- Medical history, physical examination, blood and urine tests, assessment of disease severity and activity.
- Chest x-ray (CXR) and computed tomography (CT) scan.
- Abdominal ultrasound.
- Six-minute walk test (6MWT): test to see how far the subject can walk in 6 minutes.
- Exercise testing and blood gases: Patients exercise on a stationary bicycle or treadmill while their heart and lung function are monitored. During the test, arterial blood gases are measured to determine the amount of oxygen and carbon dioxide in the blood.
- Pulmonary function tests (PFT): Patients are asked to breathe deeply and, occasionally, to hold their breath. They may be given a medicine called albuterol that dilates the airways.
- Maximum incremental ventilatory performance test (MIVP): Patients breathe normally through a mouth piece. The test system makes it increasingly difficult to inhale. Patients stop when they feel fatigued.
- Exhaled nitric oxide and carbon monoxide (Exhaled NO and CO): Patients breathe out into a tube that collects exhaled air (gases).
- Bronchoscopy and lavage: The patient's mouth and throat are numbed with lidocaine; a sedative and morphine-like drug are given for comfort. A tube is passed through the nose or mouth into the lung airways to examine the airways. Saline (salt water) is then injected through the bronchoscope into the air passage, and a sample of fluid is withdrawn for microscopic examination. Patients who do not have confirmation of their lung disease may also undergo biopsy at the time of lavage. For the biopsy, a small piece of tissue is extracted from the wall of the breathing tubes (bronchi) or the lymph nodes.
Interim testing at 6, 12, 18 and 36 weeks includes PFT, MIVP, Exhaled NO and CO, CXR, questionnaire, blood tests, and 6MWT.
Six months after completing the study, participants fill out a questionnaire.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Atorvastatin as a Disease Modifying Agent in Stage II and III Pulmonary Sarcoidosis: A Randomized, Double-Blind, Placebo-Controlled Trial|
- The duration of the steroid sparing period. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Pulmonary function [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||January 2006|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
|Placebo Comparator: 1||
Placebo vs. Atorvastatin
|Active Comparator: 2||
Placebo vs. Atorvastatin
Sarcoidosis is a multi-system granulomatous inflammatory disease. Pulmonary involvement is most common. Patients typically experience fatigue, weakness and dyspnea. Respiratory muscle weakness, which may be secondary to granulomatous inflammation, is associated with dyspnea and decreased quality of life (QOL). The disease can remit spontaneously or become chronic, with exacerbations and remissions. In some patients, it can progress to pulmonary fibrosis and death. Granulomatous inflammation is characterized primarily by accumulation of monocytes, macrophages and activated T-lymphocytes, with increased production of key inflammatory mediators, TNF-alpha, INF-gamma, IL-2 and IL-12, characteristic of a Th1-polarized response (T-helper lymphocyte-1 response). Corticosteroids are the current mainstay of treatment, but their long-term benefits are not certain. Because steroids often produce undesirable side effects, investigations to identify alternative therapies are warranted. There is sufficient evidence to test the proof of concept that pathways targeted by statins will have a therapeutic effect in sarcoidosis, since, in pre-clinical studies, statins blunt Th1-mediated inflammatory responses.
The study involves a double-blind placebo-controlled, randomized trial which aims to determine if atorvastatin administration results in less steroid use and longer steroid-free intervals in patients with pulmonary sarcoidosis who require prednisone treatment.
Patients, who are 18-70 years old, with stage II or III pulmonary sarcoidosis, diagnosed by a compatible clinical history and supported by a lung, lymph node, or tissue biopsy, will be enrolled in the study, if they require prednisone therapy. The patients will be randomly assigned to two groups; as prednisone is tapered, one group will receive placebo and the other, atorvastatin. The two study drugs will be administered for twelve months, during which time patients will be periodically evaluated as to their clinical status and prednisone requirements. Pill counts and patient diaries will be used to determine the amount of steroid use during the study period. Patients with pulmonary fibrosis greater than 50 percent of total lung volume or severe co-morbidities will be excluded from the trial.
The primary endpoint is the duration of the steroid-sparing period. Secondary clinical and physiological endpoints are intended to analyze possible anti-inflammatory and beneficial effects of the drugs. Since there is no gold standard outcome measure in sarcoidosis, four categories of secondary endpoints will be used to characterize the effects of the therapeutic agent on the clinical course of the disease: imaging (high resolution chest CT); quality of life assessments (SF-36, and SGRQ), anti-inflammatory effects (biomarkers and relapse rates), and functional effects (CPET, PFTs). Finally, we will study the utility of exhaled nitric oxide and carbon monoxide in monitoring disease activity.
|Contact: Sandra D MacDonald, R.N.||(301) firstname.lastname@example.org|
|Contact: Joseph R Fontana, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Joseph R Fontana, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|