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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: pioglitazone

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

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pioglitazone; All subjects treated for 28 days with pioglitazone, 30 mg orally, once daily Other names: Actos, Takeda	Drug: pioglitazone; All subjects treated for 28 days with pioglitazone, 30 mg orally, once daily.; Other Names: Actos; Takeda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sputum White Cell Count	The total number of white cells log 10 cells/mL	Day 0 and Day 29
Sputum Neutrophil Count	sputum neutrophils log 10 (cells/mL)	Day 0 and Day 29
Sputum Neutrophil Percent	Neutrophils as a percent of the total white cells.	Day 0 and Day 29
Sputum Active Elastase	Log 10 of Concentration of active Elastase in mcg/mL	Day 0 and Day 29
Sputum TNFα	The concentration of Tumor Necrosis Factor-α (TNFα) log 10 (pg/mL)	Day 0 and Day 29
Sputum IL-1ß	The concentration of Interleukin-1ß (IL-1ß) log 10 (pg/mL)	Day 0 and Day 29
Sputum IL-6	The concentration of Interleukin-6 (IL-6) log 10 (pg/mL)	Day 0 and Day 29
Sputum IL-8	Concentration of Interleukin-8 log 10 (pg/mL)	Day 0 and Day 29

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Michael W. Konstan, MD, Case University and Rainbow Babies and Children's Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): April 1, 2007

Study Registration Dates

• First Submitted: May 4, 2006
• First Submitted That Met QC Criteria: May 4, 2006
• First Posted (Estimate): May 8, 2006

Study Record Updates

• Last Update Posted (Actual): February 23, 2018
• Last Update Submitted That Met QC Criteria: February 21, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Kinetics; Prescription drugs; Administration, oral; Durable medical equipment
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Lung Diseases; Cystic Fibrosis; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: CFFTI-Pio001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individualized personal data (IPD) will not be shared