Losartan and Inflammation in Cystic Fibrosis

November 12, 2020 updated by: Matthias Salathe, University of Miami

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

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
7

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami, Miller School of Medicine
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Losartan group
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).
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.
Other Names:
  • Cozaar
Placebo Comparator: Placebo group
Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Drug: 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.
Other Names:
  • matching placebo twice daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Nasal Potential Difference (NPD) to Assess CFTR Activity
Time Frame: 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.
Baseline, 12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in NPD to Assess CaCC Activity
Time Frame: 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.
Baseline, 12 weeks
Change in NPD to Assess BK Activity
Time Frame: 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.
Baseline, 12 weeks
Change in FEV1
Time Frame: Baseline, 12 weeks
Forced Expiratory Volume in 1 second (FEV1) assessed in liters will be measured using spirometry.
Baseline, 12 weeks
Change in Sweat Chloride Concentration
Time Frame: Baseline, 12 weeks
Sweat chloride concentration will be analyzed from participant sweat samples analyzed in millimoles per liter (mmol/l)
Baseline, 12 weeks
Change in Quality of Life (QoL) Scores as Assessed by the CFQ-R
Time Frame: 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.
Baseline, 12 weeks
Change in Cytokine Levels
Time Frame: 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.
Baseline, 12 weeks
Change in hsCRP
Time Frame: Baseline, 12 weeks
Serum samples will be analyzed for High sensitivity C-Reactive Protein (hsCRP) values in mg/L.
Baseline, 12 weeks
Change in Blood Count Values
Time Frame: Baseline, 12 weeks
Serum blood count values including white blood count (WBC) and Absolute Neutrophil Counts (ANC) will be evaluated in units/uL.
Baseline, 12 weeks
Change in %PMN Values
Time Frame: Baseline, 12 weeks
Serum samples will be analyzed for % Polymorphonuclear (PMN) cells.
Baseline, 12 weeks
Change in SAA Values
Time Frame: Baseline, 12 weeks
Serum samples will be analyzed for Serum Amyloid A (SAA) values in mg/L.
Baseline, 12 weeks
Change in Calprotectin Values
Time Frame: Baseline, 12 weeks
Serum samples will be analyzed for calprotectin values in ug/mg.
Baseline, 12 weeks
Change in GM-CSF Values
Time Frame: Baseline, 12 weeks
Serum samples will be analyzed for % Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) values in pg/mL.
Baseline, 12 weeks
Change in TGF-beta Values
Time Frame: Baseline, 12 weeks
Serum samples will be analyzed for TGF-beta values in ng/mL.
Baseline, 12 weeks
Change in mRNA Expression
Time Frame: 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).
Baseline, 12 weeks
Change in Losartan Metabolites Levels
Time Frame: Baseline, 12 weeks
Change in serum blood levels of Losartan and Losartan metabolites EXP3179 & EXP3174.
Baseline, 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Miami

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Alabama at Birmingham
University of Kansas Medical Center
Children's Hospital Medical Center, Cincinnati
Cystic Fibrosis Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Matthias Salathe, MD, University of Miami

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 11, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 24, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 29, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 2, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 27, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 12, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20170397
  • 20170333 (Other Identifier: Human Subject Research Office at University of Miami)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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