Effect of Losartan in Cystic Fibrosis (CF)-NIH Grant #133240

Inclusion Criteria:

• CF patients with any known mutation combination not on CFTR augmentation therapy

• ≥18 years of age

• Severity of the Disease: Suitable patients will have mild to moderate lung disease,as defined by:

• Pulmonary Function: Each patient must have an FEV1 ≥40% of predicted at thescreening visit.

• Hemoglobin saturation: Patients must have an oxygen saturation of >92% on roomair as determined by pulse oximetry at the screening visit.

• Produces sputum regularly (daily basis, at minimum)

• FEV1 ≥ 40% of predicted at screening visit

• Able to sign Informed consent

• Negative COVID-19 test within 72 hours prior to MCC testing

Exclusion Criteria:

• When enrolling female patients

• Not willing to adhere to strict birth control (combination of two methods)

• If female, patient must be non-pregnant and non-lactating, and those of childbearingpotential must be using an acceptable method of birth control (i.e., an IntrauterineContraceptive Device with a failure rate of <1%, hormonal contraceptives or abarrier method). If a female patient is abstinent, she must agree to use one of theacceptable methods if she becomes sexually active.

• Unstable lung disease: As defined by a change in medical regimen during thepreceding 2 weeks or an FEV1 ≥15% below value within 3 months

• Received an investigational drug or therapy during the preceding 30 days

• Active or former smokers with less than 1 year since quitting, or >10 pack-yearsmoking history

• Unable to adequately complete study measures, including spirometry

• Intolerance to angiotensin receptor blockers (ARB)

• Treatment with angiotensin converting enzyme (ACE) inhibitor

• Regular use of NSAIDs or potassium supplementation, treatment with aliskiren, onanticoagulation

• Oral corticosteroid use within 6 weeks

• Exacerbation requiring treatment within 6 weeks

• Treatment of mycobacterial infections

• Significant hypoxemia (oxygen saturation <92% on room air and rest or use ofcontinuous oxygen treatment), chronic respiratory failure by history (pCO2 > 45mmHg), clinical evidence of cor pulmonale

• Untreated arterial hypertension (systolic blood pressure >140 mm Hg, diastolic bloodpressure > 90 mmHg)

• Blood pressure less than 90 mm Hg systolic while standing

• Cardiac, renal (creatinine 1.5 times normal limit), hepatic (LFTs > 3x normal upperlimit), neurological, psychiatric, endocrine or neoplastic diseases that are judgedto interfere with participation in study

• Known renal artery stenosis

• Concomitant airway disorders other than CF, such as ABPA

• Subjects with prior thoracic surgery

• Other severe acute or chronic medical or psychiatric condition or laboratoryabnormality that may increase the risk associated with trial participation or mayinterfere with the interpretation of trial results and, in the judgment of the PI,would make the subject inappropriate for enrollment.

• Patients using intermittent inhaled or oral antibiotics will be allowed toparticipate in this trial. Patients on chronic, cycling antibiotics will be requiredto have completed at least 2 full cycles of the prescribed antibiotic prior toenrollment and should be studied during the same phase of treatment (on or off)during each study period.

• Have had radiation exposure within the past year that would cause them to exceedFederal Regulations by participating in this study.