Cystic FibrosisPhase 2NCT03206788
Losartan and Inflammation in Cystic Fibrosis
A Phase 2 study testing Losartan in people with Cystic Fibrosis, run by University of Miami at 4 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Losartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 4 sitesUnited States
- Study dates
- 11 Nov 2017to 30 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of Kansas
Kansas City, Kansas, 66160
University of Miami, Miller School of Medicine
Miami, Florida, 33136
About this study
Official title: 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.
- Conditions
- Cystic Fibrosis
- Being tested
- Losartan, placebo
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Also called Cozaar
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.
placeboDrug
Also called matching placebo twice daily
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.
| Study group | Role | What they receive |
|---|---|---|
| Losartan group | Experimental | 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). Receives: Drug: Losartan |
| Placebo group | Placebo comparator | Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 12 weeks
Secondary outcomes (15)
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.
Measured: Baseline, 12 weeks
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.
Measured: Baseline, 12 weeks
Change in FEV1
Forced Expiratory Volume in 1 second (FEV1) assessed in liters will be measured using spirometry.
Measured: Baseline, 12 weeks
Change in Sweat Chloride Concentration
Sweat chloride concentration will be analyzed from participant sweat samples analyzed in millimoles per liter (mmol/l)
Measured: Baseline, 12 weeks
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.
Measured: Baseline, 12 weeks
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.
Measured: Baseline, 12 weeks
Change in hsCRP
Serum samples will be analyzed for High sensitivity C-Reactive Protein (hsCRP) values in mg/L.
Measured: Baseline, 12 weeks
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.
Measured: Baseline, 12 weeks
Change in %PMN Values
Serum samples will be analyzed for % Polymorphonuclear (PMN) cells.
Measured: Baseline, 12 weeks
Change in SAA Values
Serum samples will be analyzed for Serum Amyloid A (SAA) values in mg/L.
Measured: Baseline, 12 weeks
Change in Calprotectin Values
Serum samples will be analyzed for calprotectin values in ug/mg.
Measured: Baseline, 12 weeks
Change in GM-CSF Values
Serum samples will be analyzed for % Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) values in pg/mL.
Measured: Baseline, 12 weeks
Change in TGF-beta Values
Serum samples will be analyzed for TGF-beta values in ng/mL.
Measured: Baseline, 12 weeks
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).
Measured: Baseline, 12 weeks
Change in Losartan Metabolites Levels
Change in serum blood levels of Losartan and Losartan metabolites EXP3179 \& EXP3174.
Measured: Baseline, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study start11 Nov 2017
- Primary completion24 Oct 2019
- Study completion30 Dec 2019
Why it stopped: due to slow enrollment and approval of the Trikafta for CF patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- University of Alabama at Birmingham, Children's Hospital Medical Center, Cincinnati, University of Kansas Medical Center, Cystic Fibrosis Foundation
- Responsible party
- Principal investigator, Matthias Salathe, University of Miami
- Investigators
- Matthias Salathe, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03206788
- Sponsor's protocol ID
- 20170397
- Other IDs
- 20170333
- Status last verified
- Nov 2020
- First submitted
- 29 Jun 2017
- Last updated
- 27 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Losartan as Anti-inflammatory Therapy to Augment F508del Cystic Fibrosis Transmembrane (CFTR) Recovery
- ClinicalTrials.gov ID
- NCT03206788
- Acronym / sponsor ID
- 20170397
- Conditions
- Cystic Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to slow enrollment and approval of the Trikafta for CF patients
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- University of Alabama at Birmingham, Children's Hospital Medical Center, Cincinnati, University of Kansas Medical Center, Cystic Fibrosis Foundation
- Study start
- 11 Nov 2017 (actual)
- Primary completion
- 24 Oct 2019 (actual)
- Study completion
- 30 Dec 2019 (actual)
- First posted
- 2 Jul 2017 (actual)
- Results
- Posted 13 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Losartan group | Experimental | Drug: LosartanParticipant 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). |
| Placebo group | Placebo comparator | Drug: placeboParticipant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LosartanAlso: Cozaar25 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. | Drug | Losartan group |
| placeboAlso: matching placebo twice dailyPlacebo 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. | Drug | Placebo group |
Primary outcome
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.
15 secondary outcomes
Change in NPD to Assess CaCC Activity
Time frame: Baseline, 12 weeks
Change in NPD to Assess BK Activity
Time frame: Baseline, 12 weeks
Change in FEV1
Time frame: Baseline, 12 weeks
Change in Sweat Chloride Concentration
Time frame: Baseline, 12 weeks
Change in Quality of Life (QoL) Scores as Assessed by the CFQ-R
Time frame: Baseline, 12 weeks
Change in Cytokine Levels
Time frame: Baseline, 12 weeks
Change in hsCRP
Time frame: Baseline, 12 weeks
Change in Blood Count Values
Time frame: Baseline, 12 weeks
Change in %PMN Values
Time frame: Baseline, 12 weeks
Change in SAA Values
Time frame: Baseline, 12 weeks
Change in Calprotectin Values
Time frame: Baseline, 12 weeks
Change in GM-CSF Values
Time frame: Baseline, 12 weeks
Change in TGF-beta Values
Time frame: Baseline, 12 weeks
Change in mRNA Expression
Time frame: Baseline, 12 weeks
Change in Losartan Metabolites Levels
Time frame: Baseline, 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthias Salathe, MD principal investigator
University of Miami
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Losartan in people with Cystic Fibrosis, run by University of Miami at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Nasal Potential Difference (NPD) to Assess CFTR Activity (time frame: Baseline, 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2020.