Losartan and Inflammation in Cystic Fibrosis
- Registration Number
- NCT03206788
- Lead Sponsor
- University of Miami
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 7
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo group placebo Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12. Losartan group Losartan Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).
- Primary Outcome Measures
Name Time Method Change in Nasal Potential Difference (NPD) to Assess CFTR Activity Baseline, 12 weeks 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.
- Secondary Outcome Measures
Name Time Method Change in GM-CSF Values Baseline, 12 weeks Serum samples will be analyzed for % Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) values in pg/mL.
Change in NPD to Assess BK Activity Baseline, 12 weeks Big Potassium (BK) activity will be measured as the change in NPD on Adenosine Triphosphate (ATP) stimulation. NPD will be assessed from nasal epithelium samples and analyzed via a voltmeter.
Change in Sweat Chloride Concentration Baseline, 12 weeks Sweat chloride concentration will be analyzed from participant sweat samples analyzed in millimoles per liter (mmol/l)
Change in Quality of Life (QoL) Scores as Assessed by the CFQ-R Baseline, 12 weeks Cystic Fibrosis Questionnaire-Revised (CFQ-R) is a quality of life questionnaire with a total score ranging from 0-100 with a higher score indicating increased quality of life.
Change in hsCRP Baseline, 12 weeks Serum samples will be analyzed for High sensitivity C-Reactive Protein (hsCRP) values in mg/L.
Change in Losartan Metabolites Levels Baseline, 12 weeks Change in serum blood levels of Losartan and Losartan metabolites EXP3179 \& EXP3174.
Change in NPD to Assess CaCC Activity Baseline, 12 weeks Potential difference of Calcium dependent Chloride Channels (CaCC) will be measured as the change in NPD on on Adenosine Triphosphate (ATP) stimulation. NPD will be measured at the nasal epithelium via a voltmeter.
Change in Blood Count Values Baseline, 12 weeks Serum blood count values including white blood count (WBC) and Absolute Neutrophil Counts (ANC) will be evaluated in units/uL.
Change in %PMN Values Baseline, 12 weeks Serum samples will be analyzed for % Polymorphonuclear (PMN) cells.
Change in SAA Values Baseline, 12 weeks Serum samples will be analyzed for Serum Amyloid A (SAA) values in mg/L.
Change in Calprotectin Values Baseline, 12 weeks Serum samples will be analyzed for calprotectin values in ug/mg.
Change in TGF-beta Values Baseline, 12 weeks Serum samples will be analyzed for TGF-beta values in ng/mL.
Change in mRNA Expression Baseline, 12 weeks Change in messenger ribonucleic acid (mRNA) expression from nasal cells evaluated via quantitative polymerase chain reaction (qPCR) for Leucine Rich Repeating Protein 26 (LRRC26) and TGF-Beta).
Change in FEV1 Baseline, 12 weeks Forced Expiratory Volume in 1 second (FEV1) assessed in liters will be measured using spirometry.
Change in Cytokine Levels Baseline, 12 weeks Nasal airway epithelial cells taken by brush will be assessed for cytokine levels including Interleukin IL-1beta, Transforming Growth Factor (TGF-beta) active and total, IL-6, IL-8 and IL-13 in pg/mL.
Trial Locations
- Locations (4)
University of Kansas
🇺🇸Kansas City, Kansas, United States
University of Miami, Miller School of Medicine
🇺🇸Miami, Florida, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States