Losartan and Inflammation in Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

Losartan as Anti-inflammatory Therapy to Augment F508del Cystic Fibrosis Transmembrane (CFTR) Recovery

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03206788
• Other study ID #: 20170397
• Secondary ID: 20170333
• Status: Terminated
• Phase: Phase 2
• Start date: November 11, 2017
• Est. completion date: December 30, 2019

Study information

• Verified date: November 2020
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: December 30, 2019
• Est. primary completion date: October 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Losartan
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
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.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Kansas	Kansas City	Kansas
United States	University of Miami, Miller School of Medicine	Miami	Florida

Sponsors (5)

Lead Sponsor	Collaborator
University of Miami	Children's Hospital Medical Center, Cincinnati, Cystic Fibrosis Foundation, University of Alabama at Birmingham, University of Kansas Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, 12 weeks
Secondary	Change in NPD to Assess CaCC Activity	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.	Baseline, 12 weeks
Secondary	Change in NPD to Assess BK Activity	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.	Baseline, 12 weeks
Secondary	Change in FEV1	Forced Expiratory Volume in 1 second (FEV1) assessed in liters will be measured using spirometry.	Baseline, 12 weeks
Secondary	Change in Sweat Chloride Concentration	Sweat chloride concentration will be analyzed from participant sweat samples analyzed in millimoles per liter (mmol/l)	Baseline, 12 weeks
Secondary	Change in Quality of Life (QoL) Scores as Assessed by the CFQ-R	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.	Baseline, 12 weeks
Secondary	Change in Cytokine Levels	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.	Baseline, 12 weeks
Secondary	Change in hsCRP	Serum samples will be analyzed for High sensitivity C-Reactive Protein (hsCRP) values in mg/L.	Baseline, 12 weeks
Secondary	Change in Blood Count Values	Serum blood count values including white blood count (WBC) and Absolute Neutrophil Counts (ANC) will be evaluated in units/uL.	Baseline, 12 weeks
Secondary	Change in %PMN Values	Serum samples will be analyzed for % Polymorphonuclear (PMN) cells.	Baseline, 12 weeks
Secondary	Change in SAA Values	Serum samples will be analyzed for Serum Amyloid A (SAA) values in mg/L.	Baseline, 12 weeks
Secondary	Change in Calprotectin Values	Serum samples will be analyzed for calprotectin values in ug/mg.	Baseline, 12 weeks
Secondary	Change in GM-CSF Values	Serum samples will be analyzed for % Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) values in pg/mL.	Baseline, 12 weeks
Secondary	Change in TGF-beta Values	Serum samples will be analyzed for TGF-beta values in ng/mL.	Baseline, 12 weeks
Secondary	Change in mRNA Expression	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).	Baseline, 12 weeks
Secondary	Change in Losartan Metabolites Levels	Change in serum blood levels of Losartan and Losartan metabolites EXP3179 & EXP3174.	Baseline, 12 weeks