Trial Outcomes & Findings for Losartan and Inflammation in Cystic Fibrosis (NCT NCT03206788)

NCT ID: NCT03206788

Last Updated: 2020-11-27

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 7 participants
• Primary outcome timeframe: Baseline, 12 weeks
• Results posted on: 2020-11-27

Participant Flow

Participant milestones

Measure	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).	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.
Overall Study STARTED	2	5
Overall Study COMPLETED	2	2
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Measure	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).	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.
Overall Study Withdrawal by Subject	0	1
Overall Study Adverse Event	0	1
Overall Study Physician Decision	0	1

Baseline Characteristics

Losartan and Inflammation in Cystic Fibrosis

Baseline characteristics by cohort

Measure	Losartan Group n=2 Participants 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).	Placebo Group n=5 Participants Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.	Total n=7 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Losartan Group n=2 Participants 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).	Placebo Group n=2 Participants Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Change in Nasal Potential Difference (NPD) to Assess CFTR Activity	-4.2 mV Standard Error 2.1	1.59 mV Standard Error 2.48

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Losartan Group n=2 Participants 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).	Placebo Group n=2 Participants Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Change in NPD to Assess CaCC Activity	2.14 mV Standard Error 1	-5.43 mV Standard Error 7.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Losartan Group n=2 Participants 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).	Placebo Group n=2 Participants Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Change in NPD to Assess BK Activity	2.14 mV Standard Error 1	-5.43 mV Standard Error 7.1

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Forced Expiratory Volume in 1 second (FEV1) assessed in liters will be measured using spirometry.

Outcome measures

Measure	Losartan Group n=2 Participants 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).	Placebo Group n=2 Participants Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Change in FEV1	-0.18 Liter Standard Error 0.18	1.85 Liter Standard Error 0.1

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Sweat chloride concentration will be analyzed from participant sweat samples analyzed in millimoles per liter (mmol/l)

Outcome measures

Measure	Losartan Group n=2 Participants 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).	Placebo Group n=2 Participants Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Change in Sweat Chloride Concentration	-2.5 mmol/l Standard Error 7.5	-3 mmol/l Standard Error 6

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Values were not measured for this outcome for all participants.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Values were not measured for this outcome for all participants.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Values were not measured for this outcome for all participants.

Serum samples will be analyzed for High sensitivity C-Reactive Protein (hsCRP) values in mg/L.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Values were not measured for this outcome for all participants.

Serum blood count values including white blood count (WBC) and Absolute Neutrophil Counts (ANC) will be evaluated in units/uL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Values were not measured for this outcome for all participants.

Serum samples will be analyzed for % Polymorphonuclear (PMN) cells.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Values were not measured for this outcome for all participants.

Serum samples will be analyzed for Serum Amyloid A (SAA) values in mg/L.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Values were not measured for this outcome for all participants.

Serum samples will be analyzed for calprotectin values in ug/mg.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Values were not measured for this outcome for all participants.

Serum samples will be analyzed for % Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) values in pg/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Values were not measured for this outcome for all participants.

Serum samples will be analyzed for TGF-beta values in ng/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Values were not measured for this outcome for all participants.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Values were not measured for this outcome for all participants.

Change in serum blood levels of Losartan and Losartan metabolites EXP3179 & EXP3174.

Outcome measures

Outcome data not reported

Adverse Events

Losartan Group

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo Group

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Losartan Group n=2 participants at risk 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).	Placebo Group n=5 participants at risk Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
General disorders nose bleed	50.0% 1/2 • Number of events 2 • 16 weeks	0.00% 0/5 • 16 weeks
Respiratory, thoracic and mediastinal disorders Nasal congestion	100.0% 2/2 • Number of events 2 • 16 weeks	0.00% 0/5 • 16 weeks
Musculoskeletal and connective tissue disorders muscle cramps	50.0% 1/2 • Number of events 2 • 16 weeks	20.0% 1/5 • Number of events 5 • 16 weeks
General disorders Sore throat	50.0% 1/2 • Number of events 1 • 16 weeks	0.00% 0/5 • 16 weeks
Nervous system disorders Headache	0.00% 0/2 • 16 weeks	60.0% 3/5 • Number of events 5 • 16 weeks
General disorders Fatigue	0.00% 0/2 • 16 weeks	20.0% 1/5 • Number of events 1 • 16 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary exacerbation	0.00% 0/2 • 16 weeks	40.0% 2/5 • Number of events 2 • 16 weeks

Additional Information

Dr. Matthias Salathe

Kansas University Medical Center

Phone: 913 588 6045

Email: msalathe@kumc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place