Phase II Study of Digitoxin to Treat Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: digitoxin; digitoxin; placebo
Intervention description: 0.05mg tabs, once daily for 28 days; 0.1mg pills, once daily for 28 days.; pill taken once daily for 28 days
Intervention MeSH terms: Digitoxin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: digitoxin; inflammatory markers; cytokines; gene expression

Summary:

      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
    

Eligibility criteria:

        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.