Losartan and Inflammation in Cystic Fibrosis

NCT03206788 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2017039720170333
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 4

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Change in NPD to Assess CaCC Activity

  Baseline, 12 weeks

• Change in NPD to Assess BK Activity

  Baseline, 12 weeks

• Change in FEV1

  Baseline, 12 weeks

• Change in Sweat Chloride Concentration

  Baseline, 12 weeks

• Change in Quality of Life (QoL) Scores as Assessed by the CFQ-R

  Baseline, 12 weeks

Study Arms (2)

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).

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.

Drug: placebo

Interventions

Losartan DRUG

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.

Also known as: Cozaar

Losartan group

placebo DRUG

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.

Also known as: matching placebo twice daily

Placebo group

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Miami: lead
• University of Alabama at Birmingham: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• University of Kansas Medical Center: collaborator
• Cystic Fibrosis Foundation: collaborator

Study Sites (4)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of Miami, Miller School of Medicine

Miami, Florida, 33136, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Losartan

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Dr. Matthias Salathe
• Organization: Kansas University Medical Center

msalathe@kumc.edu

913 588 6045

Study Officials

• Matthias Salathe, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Emeritus Professor

Study Record Dates

• First Submitted: June 29, 2017
• First Posted: July 2, 2017
• Study Start: November 11, 2017
• Primary Completion: October 24, 2019
• Study Completion: December 30, 2019
• Last Updated: November 27, 2020
• Results First Posted: November 13, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)