Losartan and Inflammation in Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: Losartan; placebo
Intervention description: 25 mg or 50 mg (based on patient's weight) Losartan tablets taken by mouth daily in the morning for week 1 followed by twice daily (one in the morning and one in the evening) on Weeks 2-12.; Placebo tablets, matching the Losartan intervention, taken by mouth daily in the morning for week 1 followed by twice daily (one in the morning and one in the evening) on Weeks 2-12.
Intervention MeSH terms: Losartan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 7.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to examine if a specific drug called losartan (Cozaar ®),
      generally used to treat high blood pressure and to protect kidneys from damage in patients
      suffering from Diabetes Mellitus, will have any effect on the nasal inflammation in patients
      with cystic fibrosis (CF). The study will be performed at the Pulmonary Division at the
      University of Miami, Cincinnati Children's Medical Hospital Center, University of Kansas
      Medical Center and University of Alabama-Birmingham.
    

Eligibility criteria:

        Inclusion Criteria:

          -  CF patients homozygous for F508del and on current treatment with Orkambi™ for at least
             3 months

          -  Age >12 years

          -  Forced expiratory volume at one second (FEV1) >/= 40% of predicted

        Exclusion Criteria:

          -  Female patients not willing to adhere to strict birth control (combination of two
             methods)

          -  Pregnancy

          -  History of intolerance to angiotensin receptor blockers (ARBs)

          -  Treatment with angiotensin converting enzyme (ACE) inhibitor

          -  NPD response to zero chloride (0Cl)/isoproterenol of > - 6.6 mV at screening (evidence
             of detectable CFTR activity at baseline)

          -  Regular use of NSAIDs or potassium supplementation, treatment with aliskiren, on
             anticoagulation

          -  Oral corticosteroid use within 6 weeks

          -  Exacerbation requiring treatment within 6 weeks

          -  Active treatment for mycobacterial infections

          -  Significant hypoxemia (oxygen saturation <90% on room air and rest or use of
             continuous oxygen treatment), chronic respiratory failure by history (pCO2 > 45 mmHg),
             clinical evidence of cor pulmonale

          -  Untreated arterial hypertension (systolic blood pressure >140 mm Hg, diastolic blood
             pressure > 90 mmHg)

          -  Blood pressure less than 90 mm Hg systolic while standing

          -  Cardiac, renal (creatinine 1.5 times normal limit), hepatic (LFTs > 3x normal upper
             limit), neurological, psychiatric, endocrine or neoplastic diseases that are judged to
             interfere with participation in study

          -  Known renal artery stenosis

          -  Concomitant airway disorders other than CF, such as allergic bronchopulmonary
             aspergillosis (ABPA).

          -  Subjects with prior thoracic surgery