Phase II Study of Digitoxin to Treat Cystic Fibrosis

• Register: ClinicalTrials.gov
• Last refreshed on: 2 May 2022
• Main ID: NCT00782288
• Date of registration: 29/10/2008
• Prospective Registration: Yes
• Primary sponsor: National Jewish Health
• Public title: Phase II Study of Digitoxin to Treat Cystic Fibrosis
• Scientific title: Phase II Study of Digitoxin to Treat Cystic Fibrosis
• Date of first enrolment: August 2010
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00782288
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Pamela L Zeitlin, MD, PhD
• Affiliation: Johns Hopkins University, School of Medicine, Pediatric Pulmonary

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 45 Years
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: digitoxin

Other: placebo

Primary Outcome(s)

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)]

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)]

Secondary Outcome(s)

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]

Change in WBC (White Blood Cell) Count by Group During Treatment Period [Time Frame: Baseline and Day 28]

Changes in Erythrocyte Sedimentation Rate (ESR) During Treatment Period. [Time Frame: Baseline and Day 28]

Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. [Time Frame: Serum PK on Days 1 (pre-dose), 7, 14, 21 and 42]

Changes in C Reactive Protein (CRP) During Treatment. [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]

Safety Indices Including Change in FEV1 in Stable CF Patients. [Time Frame: Baseline and Day 28]

Secondary ID(s)

FD-R-003456-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 22/01/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00782288