Phase II Study of Digitoxin to Treat Cystic Fibrosis

NCT00782288 | Completed Phase 2 Results DMC

• 1 other identifier: FD-R-003456-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Cystic Fibrosis

Keywords

digitoxin; inflammatory markers; cytokines; gene expression

Outcome Measures

Primary Outcomes (4)

• Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients.

  The Il-8 measurements of sputum digitoxin levels for each group is shown for 5 days (Days 1, 14, 21, 28 and 42).

  42 days (Day 1 to Day 42)

• Change in Il-8 (Interleukin 8) Levels From Day 28 Minus Day 1 (Treatment Period).

  Change in Il-8 values are expressed as a change in log 10 Il-8 pg/mL from Day 28 minus Day 1.

  28 days (Day 28 minus Day 1)

• Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients.

  The neutrophil counts were measured in the induced sputum of participants in each group on study 5 days (Days 1, 14, 21, 28 and 42).

  42 days (Day 1- Day 42)

• Change in Neutrophil Cell Count Day 28 Minus Day 1 (Treatment Period).

  The change in log 10 neutrophil cell count from Day 28 minus Day 1 (during the treatment period) expressed as log (10\^4 neutrophil/mL).

  28 days (Day 28 minus Day 1)

Secondary Outcomes (9)

• Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients.

  Serum PK on Days 1 (pre-dose), 7, 14, 21 and 42

• Safety Indices Including Change in FEV1 in Stable CF Patients.

  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).

  Baseline and Day 42

• Change in WBC (White Blood Cell) Count by Group During Treatment Period

  Baseline and Day 28

• Changes in C Reactive Protein (CRP) During Treatment.

  Baseline and Day 28

Study Arms (3)

1

ACTIVE COMPARATOR

low dose 0.05mg digitoxin given once daily for 28 days

Drug: digitoxin

2

ACTIVE COMPARATOR

higher dose 0.1mg digitoxin daily for 28 days

Drug: digitoxin

3

PLACEBO COMPARATOR

placebo given daily for 28 days

Other: placebo

Interventions

digitoxin DRUG

0.05mg tabs, once daily for 28 days

1

placebo OTHER

pill taken once daily for 28 days

3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Use of an investigational agent within the 4-week period prior to Screen visit.
• 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

Sponsors & Collaborators

• National Jewish Health: lead

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• Zeitlin PL, Diener-West M, Callahan KA, Lee S, Talbot CC Jr, Pollard B, Boyle MP, Lechtzin N. Digitoxin for Airway Inflammation in Cystic Fibrosis: Preliminary Assessment of Safety, Pharmacokinetics, and Dose Finding. Ann Am Thorac Soc. 2017 Feb;14(2):220-229. doi: 10.1513/AnnalsATS.201608-649OC.

  PMID: 28006108 DERIVED

Related Links

• Johns Hopkins Cystic Fibrosis website

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Digitoxin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Limitations and Caveats

Steady states of digitoxin were not achieved in subjects until relatively late the in 28 day treatment period. This would suggest that it may require a much longer treatment course to meaningfully effect inflammation in the airways.

Results Point of Contact

• Title: Pamela L. Zeitlin, M.D., Ph.D., Professor and Director of SOM Pediatric Pulmonary
• Organization: Johns Hopkins University

pzeitlin@jhmi.edu

443-287-8981

Study Officials

• Pamela L Zeitlin, MD, PhD

  Johns Hopkins University, School of Medicine, Pediatric Pulmonary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: October 29, 2008
• First Posted: October 31, 2008
• Study Start: August 1, 2010
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: April 21, 2022
• Results First Posted: January 22, 2016

Record last verified: 2019-03

Locations

US (1)