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Safety and Efficacy of Pioglitazone as an Anti-inflammatory for the Treatment of Cystic Fibrosis (CF) Lung Disease

A Pilot Study Assessing the Safety and Efficacy of Pioglitazone as an Anti-inflammatory Agent for the Treatment of CF Lung Disease in Patients With Cystic Fibrosis

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00322868
Enrollment
21
Registered
2006-05-08
Start date
2006-04-30
Completion date
2007-04-30
Last updated
2018-02-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cystic Fibrosis

Keywords

Prescription drugs, Administration, oral, Durable medical equipment, Kinetics

Brief summary

Study Hypothesis: Pioglitazone may decrease inflammation in cystic fibrosis lung disease. Primary outcomes: Markers of inflammation (neutrophils, elastase, cytokines and bacteria)will be measured in induced sputum specimens before and after a 4 week treatment period with pioglitazone in clinically stable CF patients.

Detailed description

* Single-center, open label study of pioglitazone in clinically stable patients with mild to moderate CF lung disease * Induced sputum will be obtained from each subject at enrollment (Baseline) and again following 28 days of pioglitazone treatment (End of Treatment) * Changes in markers of inflammation in the sputum samples will be assessed * Safety measures, including complete blood count (CBC), serum chemistry, Erythrocyte sedimentation rate (ESR), C-Reactive Protein (CRP), urinalysis and spirometry, will also be assessed

Interventions

DRUGpioglitazone

All subjects treated for 28 days with pioglitazone, 30 mg orally, once daily.

Sponsors

Cystic Fibrosis Foundation
CollaboratorOTHER
University Hospitals Cleveland Medical Center
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Masking description

This was open-label and no one was masked.

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Male or female \>= 28 years of age * Confirmed diagnosis of cystic fibrosis * Forced Expiratory Volume in 1 second (FEV1) \>= 40% predicted * Clinically stable * Ability to reproduce spirometry * Ability to understand and sign the informed consent

Exclusion criteria

* Use of an investigational agent within 4-week period prior to Visit 1 * Chronic daily use of ibuprofen or other NSAIDS * Chronic daily use of insulin,oral diabetic agents or oral hypoglycemic agents * History of hypersensitivity to beta agonists * History of hypersensitivity to glitazones * Oxygen saturation\<92% * Pregnant, breastfeeding or unwilling to practice acceptable birth control * History of hemoptysis \>30cc per episode within 30 days prior to Visit 1 * Significant history of hepatic, cardiovascular, renal,neurologic, hematologic or peptic ulcer disease * Serum Glutamic-Oxaloacetic Transaminase (SGOT)/(Serum Glutamic Pyruvic Transaminase (SGPT) \>3 times the upper limit of normal at screening, documented biliary cirrhosis,or portal hypertension * Creatinine \> 1.8 mg/dL at screening * Inability to swallow pills * Presence or abnormality that in the opinion of the investigator would compromise the safety or the quality of the data * Subjects who have routinely taken ibuprofen or other NSAIDS; prednisone or other systemic corticosteroids, or insulin, or oral diabetic agents within 4 weeks prior to visit 1 or who have taken these medications as needed within 72 hours prior to visit one will be excluded

Design outcomes

Primary

MeasureTime frameDescription
Sputum White Cell CountDay 0 and Day 29The total number of white cells log 10 cells/mL
Sputum Neutrophil CountDay 0 and Day 29sputum neutrophils log 10 (cells/mL)
Sputum Neutrophil PercentDay 0 and Day 29Neutrophils as a percent of the total white cells.
Sputum Active ElastaseDay 0 and Day 29Log 10 of Concentration of active Elastase in mcg/mL
Sputum TNFαDay 0 and Day 29The concentration of Tumor Necrosis Factor-α (TNFα) log 10 (pg/mL)
Sputum IL-1ßDay 0 and Day 29The concentration of Interleukin-1ß (IL-1ß) log 10 (pg/mL)
Sputum IL-6Day 0 and Day 29The concentration of Interleukin-6 (IL-6) log 10 (pg/mL)
Sputum IL-8Day 0 and Day 29Concentration of Interleukin-8 log 10 (pg/mL)

Countries

United States

Participant flow

Recruitment details

All patients who will be approached for participation in this trial will first be identified using either Port CF (CFF Registry) or CF Center database. Once potentials are identified a chart review will be conducted to determine eligibility. Patients will approached at clinic for possible participation in the study.

Pre-assignment details

Washout: A 4 week washout from chronic use of NSAIDs, corticosteroids and oral meds to treat diabetes will be required. Subjects will be excluded if they take these medication within 72 hours of Visit 1. Subjects using alternate month tobramycin for inhalation (TOBI) will need to be on an off cycle to participate in this study.

Participants by arm

ArmCount
Pioglitazone (30 mg)
After screening eligibility requirements were met, cystic fibrosis subjects received pioglitazone orally, 30 mg, once daily, for 28 days
21
Total21

Withdrawals & dropouts

PeriodReasonFG000
Overall Studydisease progression1

Baseline characteristics

CharacteristicPioglitazone (30 mg)
Age, Continuous30 years
STANDARD_DEVIATION 9.28
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
20 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
percent neutrophils82.47 percent of white blood cells
STANDARD_DEVIATION 11.88
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
0 Participants
Race (NIH/OMB)
Black or African American
2 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
White
18 Participants
Region of Enrollment
United States
20 Participants
Sex: Female, Male
Female
8 Participants
Sex: Female, Male
Male
12 Participants
Total neutrophil count6.88 Log 10 (PMN/mL)
STANDARD_DEVIATION 0.39
Total white cell count6.93 log 10 (cells/mL)
STANDARD_DEVIATION 0.4

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
1 / 20
serious
Total, serious adverse events
0 / 20

Outcome results

Primary

Sputum Active Elastase

Log 10 of Concentration of active Elastase in mcg/mL

Time frame: Day 0 and Day 29

Population: Of the 20 enrolled subjects, one did not produce sputum at Baseline and a second subject's Post-Treatment sputum sample was lost due to a lab error. This reduced the number of subjects per group to 19. Of these 19 subjects, 18 subjects had both Baseline and Post-Treatment sputum samples.

ArmMeasureValue (MEAN)Dispersion
BaselineSputum Active Elastase2.03 log 10 (mcg/mL)Standard Deviation 0.36
Post-TreatmentSputum Active Elastase1.96 log 10 (mcg/mL)Standard Deviation 0.36
p-value: 0.5t-test, 1 sided
Primary

Sputum IL-1ß

The concentration of Interleukin-1ß (IL-1ß) log 10 (pg/mL)

Time frame: Day 0 and Day 29

Population: Of the 20 enrolled subjects, one did not produce sputum at Baseline and a second subject's Post-Treatment sputum sample was lost due to a lab error. This reduced the number of subjects per group to 19. Of these 19 subjects, 18 subjects had both Baseline and Post-Treatment sputum samples.

ArmMeasureValue (MEAN)Dispersion
BaselineSputum IL-1ß4.05 log 10 (pg/mL)Standard Deviation 0.42
Post-TreatmentSputum IL-1ß3.99 log 10 (pg/mL)Standard Deviation 0.52
p-value: 0.5t-test, 1 sided
Primary

Sputum IL-6

The concentration of Interleukin-6 (IL-6) log 10 (pg/mL)

Time frame: Day 0 and Day 29

Population: Of the 20 enrolled subjects, one did not produce sputum at Baseline and a second subject's Post-Treatment sputum sample was lost due to a lab error. This reduced the number of subjects per group to 19. Of these 19 subjects, 18 subjects had both Baseline and Post-Treatment sputum samples.

ArmMeasureValue (MEAN)Dispersion
BaselineSputum IL-61.38 log 10 (pg/mL)Standard Deviation 0.33
Post-TreatmentSputum IL-61.41 log 10 (pg/mL)Standard Deviation 0.32
p-value: 0.55t-test, 1 sided
Primary

Sputum IL-8

Concentration of Interleukin-8 log 10 (pg/mL)

Time frame: Day 0 and Day 29

Population: Of the 20 enrolled subjects, one did not produce sputum at Baseline and a second subject's Post-Treatment sputum sample was lost due to a lab error. This reduced the number of subjects per group to 19. Of these 19 subjects, 18 subjects had both Baseline and Post-Treatment sputum samples.

ArmMeasureValue (MEAN)Dispersion
BaselineSputum IL-85.13 log 10 (pg/mL)Standard Deviation 0.35
Post-TreatmentSputum IL-85.10 log 10 (pg/mL)Standard Deviation 0.34
p-value: 0.75t-test, 1 sided
Primary

Sputum Neutrophil Count

sputum neutrophils log 10 (cells/mL)

Time frame: Day 0 and Day 29

Population: Of the 20 enrolled subjects, one did not produce sputum at Baseline and a second subject's Post-Treatment sputum sample was lost due to a lab error. This reduced the number of subjects per group to 19. Of these 19 subjects, 18 subjects had both Baseline and Post-Treatment sputum samples.

ArmMeasureValue (MEAN)Dispersion
BaselineSputum Neutrophil Count6.88 log 10 (cells/mL)Standard Deviation 0.39
Post-TreatmentSputum Neutrophil Count6.75 log 10 (cells/mL)Standard Deviation 0.42
p-value: 0.2467t-test, 1 sided
Primary

Sputum Neutrophil Percent

Neutrophils as a percent of the total white cells.

Time frame: Day 0 and Day 29

Population: Of the 20 enrolled subjects, one did not produce sputum at Baseline and a second subject's Post-Treatment sputum sample was lost due to a lab error. This reduced the number of subjects per group to 19. Of these 19 subjects, 18 subjects had both Baseline and Post-Treatment sputum samples.

ArmMeasureValue (MEAN)Dispersion
BaselineSputum Neutrophil Percent82.47 Percent (%) of white blood cellsStandard Deviation 11.88
Post-TreatmentSputum Neutrophil Percent74.44 Percent (%) of white blood cellsStandard Deviation 17.07
p-value: 0.0288t-test, 1 sided
Primary

Sputum TNFα

The concentration of Tumor Necrosis Factor-α (TNFα) log 10 (pg/mL)

Time frame: Day 0 and Day 29

Population: Of the 20 enrolled subjects, one did not produce sputum at Baseline and a second subject's Post-Treatment sputum sample was lost due to a lab error. This reduced the number of subjects per group to 19. Of these 19 subjects, 18 subjects had both Baseline and Post-Treatment sputum samples.

ArmMeasureValue (MEAN)Dispersion
BaselineSputum TNFα1.74 log 10 (pg/mL)Standard Deviation 0.49
Post-TreatmentSputum TNFα1.69 log 10 (pg/mL)Standard Deviation 0.59
p-value: 0.62t-test, 1 sided
Primary

Sputum White Cell Count

The total number of white cells log 10 cells/mL

Time frame: Day 0 and Day 29

Population: Of the 20 enrolled subjects, one did not produce sputum at Baseline and a second subject's Post-Treatment sputum sample was lost due to a lab error. This reduced the number of subjects per group to 19. Of these 19 subjects, 18 subjects had both Baseline and Post-Treatment sputum samples.

ArmMeasureValue (MEAN)Dispersion
BaselineSputum White Cell Count6.93 log 10 (cells/mL)Standard Deviation 0.4
Post-TreatmentSputum White Cell Count6.81 log 10 (cells/mL)Standard Deviation 0.41
p-value: 0.2772t-test, 1 sided

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026