Treatment of Pulmonary Sarcoidosis With Pentoxifylline
N/A
N/A
Both
Pulmonary Sarcoidosis
Trial Information
Treatment of Pulmonary Sarcoidosis With Pentoxifylline
Corticosteroids are currently the mainstay of therapy for active pulmonary sarcoidosis and
are used to prevent relapses in many patients with stable disease. The pulmonary
manifestations of sarcoidosis are heterogenous and not all patients require corticosteroid
therapy. Corticosteroids often produce undesirable side effects and, therefore, other
therapies that can reduce or replace corticosteroid use are being sought. As tumor necrosis
factor-alpha (TNF-alpha) plays a pivotal role in the formation of granulomata (the
pathological hallmark of the disease), drugs that inhibit its production/release may prove
effective in the treatment of this disease. Pentoxifylline (POF), a xanthine derivative
used for many years in the treatment of peripheral vascular disease, is known to inhibit
TNF-alpha release by human peripheral blood mononuclear cells and alveolar macrophages from
patients with active sarcoidosis. To evaluate whether this drug is beneficial in the
treatment of sarcoidosis, we propose to conduct a randomized, double-blind,
placebo-controlled trial with POF in patients with pulmonary sarcoidosis on corticosteroid
therapy. The primary objective of this study is to determine whether POF treatment can be
beneficial as an adjunct to corticosteroid therapy in patients with pulmonary sarcoidosis.
The role of TNF-alpha and other cytokines (released from alveolar macrophages) in explaining
treatment responses defined by whether or not a patient improved will be assessed by testing
whether the effect of treatment on the probability of improvement varies with cytokine
levels.
Inclusion Criteria
INCLUSION CRITERIA:
1. Admission to this protocol will require a diagnosis of pulmonary sarcoidosis with or
without ocular sarcoidosis based on clinical history, and biopsy of either lung,
intrathoracic or other lymph nodes, or internal organs consistent with sarcoidosis,
with all other causes of granuloma ruled out. Prior to enrollment in the study,
patients will have their biopsy slides reviewed by a pathologist for confirmation of
the diagnosis.
2. Males or females between 18 and 70 years of age on corticosteroid therapy.
EXCLUSION CRITERIA:
1. Patients with active sarcoidosis of major organs other than the lungs and eyes (e.g.,
central nervous system, cardiac, renal) that require corticosteroid therapy.
2. Patients with uncontrolled hypertension, uncontrolled diabetes, history of cerebral
or retinal hemorrhage, heart failure (New York class III or higher), renal failure
(on dialysis), liver failure (with portal hypertension and ascites), cancer EXCEPT
non-metastatic basal or squamous cell carcinoma of the skin, hematologic disorders,
including severe anemia (hemoglobin less than or equal to 7 g/dl), granulocytopenia,
platelet disorders, or a need for anticoagulation therapy.
3. Patients with concomitant obstructive lung disease (i.e., asthma, COPD, cystic
fibrosis) or other interstitial lung diseases since changes in pulmonary function in
such patients could not be attributed to sarcoidosis alone.
4. Patients who are pregnant or lactating.
5. Women of child-bearing potential without an accepted method of birth control.
6. Patients with a positive serum test for human immunodeficiency virus or hepatitis B
or C virus.
7. Patients incapable of giving informed consent.
8. Patients allergic to POF or methylxanthines such as caffeine, theophylline and
theobromine.
9. Patients currently taking corticosteroids for disease other than pulmonary
sarcoidosis, theophylline, POF, or other xanthines, or patients who have been on
these drugs in the preceding three months.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
Authority:
United States: Federal Government
Study ID:
990057
NCT ID:
NCT00001877
Start Date:
February 1999
Completion Date:
May 2004
Related Keywords:
- Pulmonary Sarcoidosis
- Tumor Necrosis Factor
- Corticosteroids
- Macrophages
- Phosphodiesterase
- Autoimmune
- Pulmonary Sarcoidosis
- Sarcoidosis
- Sarcoidosis, Pulmonary
Name | Location |
|---|---|
| National Heart, Lung and Blood Institute (NHLBI) | Bethesda, Maryland 20892 |
