Clinical trial NCT03206788: Losartan and Inflammation in Cystic Fibrosis
Official title: Losartan as Anti-inflammatory Therapy to Augment F508del Cystic Fibrosis Transmembrane (CFTR) Recovery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: University of Alabama at Birmingham
name: Children's Hospital Medical Center, Cincinnati
name: University of Kansas Medical Center
name: Cystic Fibrosis Foundation
First posted: 2017-07-02
Enrollment: 7
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Change in Nasal Potential Difference (NPD) to Assess CFTR Activity
timeFrame: Baseline, 12 weeks
Secondary outcomes:
measure: Change in NPD to Assess CaCC Activity
timeFrame: Baseline, 12 weeks
measure: Change in NPD to Assess BK Activity
timeFrame: Baseline, 12 weeks
measure: Change in FEV1
timeFrame: Baseline, 12 weeks
measure: Change in Sweat Chloride Concentration
timeFrame: Baseline, 12 weeks
measure: Change in Quality of Life (QoL) Scores as Assessed by the CFQ-R
timeFrame: Baseline, 12 weeks
measure: Change in Cytokine Levels
timeFrame: Baseline, 12 weeks
measure: Change in hsCRP
timeFrame: Baseline, 12 weeks
measure: Change in Blood Count Values
timeFrame: Baseline, 12 weeks
measure: Change in %PMN Values
timeFrame: Baseline, 12 weeks
measure: Change in SAA Values
timeFrame: Baseline, 12 weeks
measure: Change in Calprotectin Values
timeFrame: Baseline, 12 weeks
measure: Change in GM-CSF Values
timeFrame: Baseline, 12 weeks
measure: Change in TGF-beta Values
timeFrame: Baseline, 12 weeks
measure: Change in mRNA Expression
timeFrame: Baseline, 12 weeks
measure: Change in Losartan Metabolites Levels
timeFrame: Baseline, 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Miami
country: United States
facility: University of Miami, Miller School of Medicine
state: Florida
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: University of Miami
name: Matthias Salathe, MD
role: PRINCIPAL_INVESTIGATOR
References: