Clinical Trial: Sildenafil for PNTM Infection

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Sildenafil in Patients With Pulmonary Nontuberculous Mycobacterial Infection

Brief Summary:

Background:

• Pulmonary nontuberculous mycobacterial (PNTM) infection is caused by a common type of bacteria in the environment. Although PNTM infection is most common in people with lung diseases, it can also affect healthy people. It can be difficult to treat, and affects parts of the body other than the lungs. For example, PNTM may affect the cilia, the hair-like structures inside the nose and lungs that help move dirt and debris out of the body.
• Ciliary beat frequency (CBF) is a measurement of how fast cilia move. People with PNTM infection have a lower CBF than healthy people. Nitric oxide (NO) is a gas in the body that may affect CBF. People with PNTM infection produce lower amounts of NO in their noses than healthy people. Researchers want to see if a drug called sildenafil can increase NO production and CBF. If sildenafil can improve these measurements, it may be a useful treatment for PNTM infection.

Objectives:

- To study the effect of sildenafil on CBF and NO levels in people with PNTM infection.

Eligibility:

• Individuals at least 18 years of age who have PNTM infection.
• Participants must be enrolled in a related National Institutes of Health study on bacterial infections. The study is Natural History, Genetics, Phenotype and Treatment of Mycobacterial Infections.

Design:

• Participants will be screened with a physical exam and medical history. They will also have heart and lung function tests,
  

  Detailed Summary:

  Pulmonary nontuberculous mycobacterial (PNTM) infection has increased over the past several decades, especially in older women. No consistent immunological abnormalities have been found despite extensive investigation. In cystic fibrosis and primary ciliary dyskinesia, mucociliary dysfunction predisposes individuals to high rates of PNTM disease that increases markedly with age.

  We studied the respiratory biology of subjects with PNTM and healthy controls and found decreased levels of nasal nitric oxide (nNO) in vivo. Ex vivo analysis of ciliated respiratory epithelium from subjects with PNTM demonstrated an abnormally low resting ciliary beat frequency (CBF) and an abnormal response to toll-like receptor ([TLR]2,TLR3, TLR5, TLR7/8, and TLR9) agonists, compared with respiratory samples from healthy controls. The low CBF response was normalized ex vivo by augmenting the nitricoxide-cyclic guanosine monophosphate pathway; this supplementation had no appreciable effect on the differences in TLR responses observed in subjects with PNTM and healthy controls. The reduced CBF and nNO levels in these subjects reveal possible mechanisms of susceptibility to respiratory infections, as well as possible avenues of directed investigation and therapy.

  This is an open-label, interventional study evaluating the effects of sildenafil on CBF in subjects with PNTM infection. The study will also measure the effects of sildenafil on nNO, and it will evaluate the quality of life, exertional capacity, pulmonary function, lower airway microbiology, inflammatory markers, and the safety and tolerability of sildenafil treatment in this population.

  The first 5 subjects will receive an oral bolus of sildenafil (40 mg) on day 0 followed by an oral dose of 20 mg 3 times a day (tid) starting on day 1 for
  Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
  

  Current Primary Outcome: Modulation of CBF with sildenafil in subjects with PNTM infection. The study will also measure the effects of sildenafil on nNO, and it will evaluate the quality of life, exertional capacity, pulmonary function, lower airway microbiology, inflam... [ Time Frame: 30 days ]
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome:
  
  

  Original Secondary Outcome:
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: May 10, 2013
  Date Started: January 2013
  Date Completion:
  Last Updated: September 24, 2015
  Last Verified: September 2015