Prostaglandin Inhibition for Emphysema
Condition: Emphysema
MeSH terms: Pulmonary Emphysema; Emphysema
Study type: Interventional
Phase: Phase 2

Summary: 
      The Prostaglandin Inhibition for Emphysema (PIE) study will determine if a currently
      available therapy, ibuprofen 600 mg three times daily, can block PGE production in the lower
      respiratory tract and if this results in improvement in measures of lung repair function.
    

Detailed description: 
      The Prostaglandin Inhibition for Emphysema (PIE) study will determine if a currently
      available therapy, ibuprofen 600 mg three times daily, can block PGE production in the lower
      respiratory tract and if this results in improvement in measures of lung repair function.
      This is a proof-of-concept study. The PIE study will set the stage for novel therapy to
      modify the course of chronic obstructive pulmonary disease (COPD).

      COPD is the third leading cause of death in the United States. No currently available
      treatment can meaningfully restore lung function that is lost in this disease. Emphysema is a
      major component of COPD and results when lung damage exceeds the ability of the lung to
      repair. Recent evidence indicates that the repair processes present in the normal lung are
      deficient in patients with emphysema and that this is due, in part, to suppression of repair
      by an inflammatory mediator: prostaglandin E (PGE). Currently available therapies can block
      PGE production, but whether this can be achieved in the lung in COPD is unknown. The PIE
      study will answer that question.

      This will be accomplished by performing a randomized, double blind, placebo-controlled,
      parallel group study that will compare a widely used and well-tolerated non-steroidal
      anti-inflammatory drug, ibuprofen 600 mg three times daily, with placebo. PGE will be
      measured directly in the lower respiratory tract by sampling the lung with the technique of
      bronchoalveolar lavage. Secondary measures will be made, quantifying PGE in induced sputum
      and quantifying PGE metabolites in blood and urine. In addition, the current proposal will
      determine if biochemical measures of lung repair are restored by treatments that block PGE
      production. Additional outcomes will also be assessed including the effect of treatment on
      PGD and other eicosanoids and assessing IL-8 and neutrophils in sputum and BAL fluid and
      selected inflammatory biomarkers present in serum that may be associated with lung function
      decline. Finally, in an accompanying Ancillary Study, the current proposal will determine if
      alveolar macrophages over-produce PGE and/or PGD in COPD and will determine if the microRNA
      miR-146a modulates the production of these prostaglandins, as we have demonstrated for lung
      fibroblasts. The Ancillary Study will also determine if genetic variation in a miR-146a is
      related to differential expression.

      The proposed research will, therefore, determine if inhibition of PGE production can be
      achieved in the lung, if this appears to restore lung repair mechanisms and will help
      determine who would benefit from such a therapeutic approach. This is a highly novel approach
      to the treatment of emphysema and has the potential to restore lost lung function, a crucial
      unmet medical need for a major public health problem.
    

Intervention name(s): 600 mg ibuprofen three times daily for 48 weeks; Placebo three times daily
Intervention type(s): Drug; Other
Other intervention name(s): Advil, Children's Ibuprofen, Advil Migraine, Motrin IB, NeoProfen, Caldolor, Wal-Profen, I-Prin
Intervention MeSH terms: Ibuprofen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Emphysema; Prostaglandin E; Bronchoalveolar lavage