Losartan and Inflammation in Cystic Fibrosis

Phase 2TerminatedNCT03206788

University of Miami7 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Cystic Fibrosis

Interventions

LosartanDRUG

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.

placeboDRUG

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.

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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

Locations (4)

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Miami, Miller School of Medicine

Miami, Florida, United States

University of Kansas

Kansas City, Kansas, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Outcomes

Primary Outcomes

Change in Nasal Potential Difference (NPD) to Assess CFTR Activity

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activity will be measured as the change in NPD in response to apical perfusion with 0 Cl-/isoproterenol. NPD will be measured at the nasal epithelium via a voltmeter.