This trial is active, not recruiting.

Condition cystic fibrosis
Treatments digitoxin, placebo
Phase phase 2
Sponsor Pamela L. Zeitlin, MD, PhD
Start date August 2010
End date June 2014
Trial size 24 participants
Trial identifier NCT00782288, FD-R-003456-01


This study will measure the inflammatory effects of digitoxin on IL-8 and neutrophil counts in induced sputum in stable Cystic Fibrosis (CF) patients and the pharmacokinetics of digitoxin in serum.

Funding Source-FDA OOPD

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
(Active Comparator)
low dose 0.05mg digitoxin given once daily for 28 days
0.05mg tabs, once daily for 28 days
(Active Comparator)
higher dose 0.1mg digitoxin daily for 28 days
0.1mg pills, once daily for 28 days.
(Placebo Comparator)
placebo given daily for 28 days
pill taken once daily for 28 days

Primary Outcomes

Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients.
time frame: 42 days (Day 1 to Day 42)
Change in Il-8 (Interleukin 8) Levels From Day 28 Minus Day 1 (Treatment Period).
time frame: 28 days (Day 28 minus Day 1)
Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients.
time frame: 42 days (Day 1- Day 42)
Change in Neutrophil Cell Count Day 28 Minus Day 1 (Treatment Period).
time frame: 28 days (Day 28 minus Day 1)

Secondary Outcomes

Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients.
time frame: Serum PK on Days 1 (pre-dose), 7, 14, 21 and 42
Safety Indices Including Change in FEV1 in Stable CF Patients.
time frame: Baseline and Day 28
Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R).
time frame: Baseline and Day 42
Change in WBC (White Blood Cell) Count by Group During Treatment Period
time frame: Baseline and Day 28
Changes in C Reactive Protein (CRP) During Treatment.
time frame: Baseline and Day 28
Changes in Erythrocyte Sedimentation Rate (ESR) During Treatment Period.
time frame: Baseline and Day 28
Number of CF Subjects With Microarray Results From Nasal Epithelial Cells to Measure the Effect of Digitoxin on Gene Expression.
time frame: Day 0 and Day 28
Clinically Significant Alterations in ECG Readings
time frame: 28 days
Clinically Significant Changes in the Microbiology of Sputum in Subjects
time frame: 28 days

Eligibility Criteria

Male or female participants from 18 years up to 45 years old.

Inclusion Criteria - Male or female 18-45 years of age - Confirmed diagnosis of CF based on the following criteria:positive sweat chloride > or = 60 mEq/liter (by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF - FEV1 > or = 40% predicted value at screening - Weight > 45 kg at Screening and Visit 1 (dosing) - Clinically stable with no evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation (see Appendix II) or treatment of a pulmonary exacerbation within the 14 days prior to Screen Visit. Subject may rescreen 14 days after they complete treatment for a pulmonary exacerbation, if healthy at that time. - Ability to perform Spirometry. - Ability to understand and sign a written informed consent and comply with the requirements of the study. Exclusion Criteria: - Use of an investigational agent within the 4-week period prior to Screen visit. - Use of a medication with anti-neutrophil or anti-inflammatory effect or those known to have an effect on inflammatory outcomes [azithromycin, gentamicin, amikacin, colistin, ibuprofen, celecoxib, or other NSAIDs, prednisone or other corticosteroids(systemic or inhaled), such as Advair, cromolyn (Intal®), montelukast (Singulair®), zafirlukast (Accolate®), zileuton (Zyflo®), and any immunosuppressive agent within the 4 weeks prior to Visit #1, Day 1 and until their participation in the study ends (after Visit 6). See NOTE at end of exclusionary criteria for subjects on oral antibiotic therapy. - Use of topical nasal steroid products for at least 2 weeks prior to study drug administration and discontinued use until after the nasal cell collection at Day 28. - Inability or unwillingness to stop macrolide antibiotics 4 weeks prior to Day 1 until their participation in the study ends. Prior use of macrolide antibiotics, including those for maintenance therapy will not exclude the subject from participation. - History of significant cardiac disease or cardiac arrhythmia - Presence of an arrhythmia identified on screening ECG or 24 hour holter monitor - Pulmonary hypertension - History of significant cardiac disease or cardiac arrhythmia - Presence of a clinically significant arrhythmia identified on screening ECG or 24 hour holter monitor. - Pulmonary hypertension - Burkholderia species in sputum within 2 years or at Screen visit - Drugs known to interact with digitoxin including phenobarbital, amphotericin B, rifampicin, diltiazem, and verapamil or drugs that would potentiate potassium loss (certain diuretics or excessive laxative use, defined as more than twice daily use of miralax). - Unwillingness to use beta-agonists (or levalbuterol) prior to induced sputum procedures. - Oxygen saturation < 92% on room air at Screen visit - Pregnant, breastfeeding, or unwilling to use an effective form of birth control for the duration of the study - History of significant hemoptysis > or = 60cc per episode during the 30 days prior to Screening visit - Significant history of hepatic, cardiovascular, renal, neurological, hematologic, or peptic ulcer disease - SGOT (ALT) or SGPT (AST) > 3 times the upper limit of normal at Screen, documented biliary cirrhosis, or portal hypertension - Creatinine > 1.8 mg/dL at Screen - Inability to swallow pills - Potassium, serum <3.3 mEq/L at screening - Known inability to produce sputum (if unable to expectorate, must be able to produce an induced sputum sample at screening). - Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the quality of the data NOTE: For subjects on continuous antibiotic therapy for at least 6 months one continuous antibiotic or alternating two different antibiotics, they can maintain their current therapy. If the subject is alternating between two different inhaled antibiotics each month, Visit 1 should coincide with the "on" cycle of one of the inhaled antibiotics for consistency during the treatment period. For subjects on alternate month TOBI®, colistin or Cayston therapy, the "off" cycle must coincide with the Treatment Phase of the study. Subjects should be scheduled for Screening Visit during their one-month "on" period, and may resume taking TOBI®, colistin or Cayston after completion of Visit 6 (Day 42) or early termination.

Additional Information

Official title Phase II Study of Digitoxin to Treat Cystic Fibrosis
Principal investigator Pamela L Zeitlin, MD, PhD
Description The study will be conducted as a randomized, double blind, placebo-controlled, repeat dosing trial evaluating the effects of 28 days of digitoxin on IL-8 and neutrophil concentrations in induced sputum in subjects with mild to moderate cystic fibrosis lung disease. Twenty-four total patients will be randomized into 3 groups of 8 subjects each (0.05 mg or 0.1 mg digitoxin or a placebo).
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Johns Hopkins University.