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Phase II Study of Digitoxin to Treat Cystic Fibrosis

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ClinicalTrials.gov Identifier: NCT00782288
Recruitment Status : Completed
First Posted : October 31, 2008
Results First Posted : January 22, 2016
Last Update Posted : September 14, 2017
Sponsor:
Information provided by (Responsible Party):
Pam Zeitlin, National Jewish Health

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: digitoxin
Other: placebo
Enrollment 24
Recruitment Details All participants were recruited from the Johns Hopkins University in Baltimore, Maryland. The first participant was enrolled on October 13, 2010 and the last participant was enrolled on May 6, 2014. All study visits were completed as of June 2014. There was a DSMB safety review prior to enrolling any subjects into the higher dose group (0.1 mg).
Pre-assignment Details Participants were all consented on a Johns Hopkins IRB approved consent form and screened 2 or 4 weeks prior to enrollment. Enrollment was contingent on meeting all inclusion/exclusion criteria.
Arm/Group Title Placebo Low Dose 0.05mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Period Title: Overall Study
Started 8 8 8
Completed 8 8 8
Not Completed 0 0 0
Arm/Group Title Placebo Low Dose 0.05 mg Digitoxin Higher Dose 0.1mg Digitoxin Total
Hide Arm/Group Description

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Total of all reporting groups
Overall Number of Baseline Participants 8 8 8 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 8 participants 24 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
8
 100.0%
8
 100.0%
8
 100.0%
24
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 8 participants 8 participants 8 participants 24 participants
24.8
(18.2 to 39.7)
23.5
(18.2 to 37.7)
30.3
(19.8 to 42.8)
26.2
(18.2 to 42.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 8 participants 24 participants
Female
4
  50.0%
5
  62.5%
4
  50.0%
13
  54.2%
Male
4
  50.0%
3
  37.5%
4
  50.0%
11
  45.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 8 participants 24 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
8
 100.0%
8
 100.0%
8
 100.0%
24
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 8 participants 8 participants 8 participants 24 participants
8 8 8 24
1.Primary Outcome
Title Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients.
Hide Description The Il-8 measurements of sputum digitoxin levels for each group is shown for 5 days (Days 1, 14, 21, 28 and 42).
Time Frame 42 days (Day 1 to Day 42)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Sputum was collected for Il-8 biomarkers on Days 1,14, 21, 28 during the treatment phase and at Day 42. Measures were compared between Baseline, Treatment and Recovery periods to determine if changes from baseline differed between placebo and the two doses.
Arm/Group Title Placebo Low Dose 0.05 mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 8 8
Median (Inter-Quartile Range)
Unit of Measure: log 10 (pg/mL)
IL-8 Day 1
4.59
(4.15 to 5.12)
4.96
(4.4 to 5.18)
5.04
(4.58 to 5.10)
IL-8 Day 14
4.94
(4.21 to 5.34)
4.89
(4.50 to 5.01)
5.01
(4.66 to 5.45)
IL-8 Day 21
5.08
(4.21 to 5.38)
4.77
(4.64 to 4.89)
5.17
(4.66 to 5.42)
IL-8 Day 28
4.66
(4.49 to 5.38)
4.79
(4.49 to 4.91)
5.20
(4.68 to 5.34)
IL-8 Day 42
4.59
(4.22 to 5.06)
4.74
(4.62 to 5.04)
4.97
(4.43 to 5.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Low Dose 0.05 mg Digitoxin, Higher Dose 0.1mg Digitoxin
Comments Measures were compared between Baseline, Treatment & Recovery periods to determine if changes from baseline differed between placebo and the two digitoxin dose levels. Kruskal-Wallis equity of population rank test was performed on the changes Day 28 minus Day 1. To compare the change from baseline to treatment period between the two arms, a Wilcoxon rank sum test was performed. To determine whether induced sputum Il-8 returned to baseline at the final visit, a one sample sign test was performed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Primary Outcome
Title Change in Il-8 (Interleukin 8) Levels From Day 28 Minus Day 1 (Treatment Period).
Hide Description Change in Il-8 values are expressed as a change in log 10 Il-8 pg/mL from Day 28 minus Day 1.
Time Frame 28 days (Day 28 minus Day 1)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
For change in Il-8 from Day 28 minus Day 1, a Kruskal-Wallis equality of populations rank was performed.
Arm/Group Title Placebo Low Dose 0.05mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 8 8
Median (Inter-Quartile Range)
Unit of Measure: log10 (pg/mL)
0.13
(0.06 to 0.40)
-0.13
(-0.23 to 0.16)
0.04
(-0.24 to 0.41)
3.Primary Outcome
Title Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients.
Hide Description 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).
Time Frame 42 days (Day 1- Day 42)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Neutrophil cell counts were compared between Baseline, Treatment and Recovery periods to determine if changes from baseline differed between the placebo and the two digitoxin dose levels.
Arm/Group Title Placebo Low Dose 0.05 mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 7 7
Median (Inter-Quartile Range)
Unit of Measure: log 10 (neutrophil cells/mL)
Day 1
2.58
(1.89 to 3.00)
2.82
(1.88 to 3.08)
2.93
(2.35 to 3.04)
Day 14
2.89
(2.18 to 2.92)
2.26
(1.35 to 2.91)
2.71
(2.26 to 3.10)
Day 21
2.86
(2.44 to 3.35)
2.23
(1.52 to 2.62)
2.88
(1.90 to 3.14)
Day 28
2.71
(2.16 to 3.06)
2.16
(0.83 to 2.64)
2.77
(1.97 to 3.01)
Day 42
2.55
(2.27 to 2.81)
2.06
(1.58 to 2.35)
2.82
(2.00 to 2.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Low Dose 0.05 mg Digitoxin, Higher Dose 0.1mg Digitoxin
Comments Baseline,Treatment and Recovery periods were compared to determine if changes from baseline differed between placebo and the two digitoxin doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Primary Outcome
Title Change in Neutrophil Cell Count Day 28 Minus Day 1 (Treatment Period).
Hide Description 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).
Time Frame 28 days (Day 28 minus Day 1)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The change in neutrophil cell count from Day 1 to Day 28 was performed using a Kruskal-Wallis equality of populations rank test. The cells counts are expressed as log 10 (neutrophil cell/mL).
Arm/Group Title Placebo Low Dose 0.05mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 7 7
Median (Inter-Quartile Range)
Unit of Measure: log 10 (neutrophil cell/mL)
0.19
(-0.24 to 0.82)
-0.26
(-0.41 to 0.29)
-0.02
(-0.33 to 0.26)
5.Secondary Outcome
Title Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients.
Hide Description Digitoxin serum levels were drawn on Days 1 (pre-dose), 7, 14, 21 and 42. The range of digitoxin levels for each visit is listed and the number of subjects who had that level are marked by group (placebo, low dose and high dose).
Time Frame Serum PK on Days 1 (pre-dose), 7, 14, 21 and 42
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Subjects had serum digitoxin levels drawn at Day 1 (pre-dose) with no levels observed, as expected. Digitoxin was drawn on Day 7, 14, 21 and 42 to determine the number of subjects with a detectable level of digitoxin (ng/mL) in serum by group.
Arm/Group Title Placebo Low Dose 0.05mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 8 8
Measure Type: Number
Unit of Measure: participants
Day 7, digitoxin level 5.6 ng/mL 0 0 1
Day 7, digitoxin level 6 ng/mL 0 1 1
Day 7, digitoxin level 6.4 ng/mL 0 0 1
Day 7, digitoxin level 6.9 ng/mL 0 0 1
Day 7, digitoxin level 7.8 ng/mL 0 0 1
Day 7, digitoxin level none detected 8 7 3
Day 14, digitoxin level 10 ng/mL 0 0 1
Day 14, digitoxin level 11 ng/mL 0 1 0
Day 14, digitoxin level 13 ng/mL 0 0 1
Day 14, digitoxin level 6.8 ng/mL 0 0 1
Day 14, digitoxin level 6.9 ng/mL 0 1 0
Day 14, digitoxin level 7.3 ng/mL 0 1 0
Day 14, digitoxin level 7.5 ng/mL 0 0 1
Day 14, digitoxin level 8.1 ng/mL 0 0 1
Day 14, digitoxin level 9.3 ng/mL 0 0 1
Day 14, digitoxin level 9.4 ng/mL 0 0 1
Day 14, digitoxin level none detected 8 5 1
Day 21, digitoxin level 10 ng/mL 0 0 1
Day 21, digitoxin level 11 ng/mL 0 0 1
Day 21, digitoxin level 12 ng/mL 0 0 1
Day 21, digitoxin level 13 ng/mL 0 0 1
Day 21, digitoxin level 14 ng/mL 0 0 1
Day 21, digitoxin level 15 ng/mL 0 1 0
Day 21, digitoxin level 4 ng/mL 0 1 0
Day 21, digitoxin level 5 ng/mL 0 1 0
Day 21, digitoxin level 6 ng/mL 0 1 0
Day 21, digitoxin level 6.4 ng/mL 0 1 0
Day 21, digitoxin level 6.5 ng/mL 0 0 1
Day 21, digitoxin level 6.9 ng/mL 0 0 1
Day 21, digitoxin level 7.5 ng/mL 0 0 1
Day 21, digitoxin level none detected 8 3 0
Day 42, digitoxin level 5 ng/mL 0 1 0
Day 42, digitoxin level none detected 8 7 8
6.Secondary Outcome
Title Safety Indices Including Change in FEV1 in Stable CF Patients.
Hide Description Safety indices included changes in FEV1 (forced expiratory volume in 1 second), changes in WBC (white blood cell count), alterations in ECG and sputum microbiology. The median changes in FEV1 are reported.
Time Frame Baseline and Day 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Median changes in FEV1 in L by group for the 28 days of treatment.
Arm/Group Title Placebo Low Dose 0.05mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 8 8
Median (Inter-Quartile Range)
Unit of Measure: liters
-0.00
(-0.37 to 0.22)
0.10
(0.05 to 0.13)
-0.02
(-0.14 to 0.07)
7.Secondary Outcome
Title Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R).
Hide Description

CFQ-R is a disease-specific instrument designed to measure impact on overall health, daily life, perceived well-being and symptoms. Developed specifically for use in patients with a diagnosis of cystic fibrosis. There are 9 Quality of life domains: physical, role/school, vitality, emotion, social, body image, eating, treatment burden, health perceptions and 3 symptom scales: weight, respiratory, and digestion.

Scaling of items is done via 5 distinct 4-point Likert scales. Scores for each domain; after recoding, each item is summed to generate a domain score and standardized. Scores range from 0 to 100, with higher scores indicating better health. Based on clinician judgment of global clinical change, a moderate change was a standardized effect size of 0.50 units and an important change was a standardized effect size of 0.80 units evaluating pre- and post-treatment for CF exacerbation. Mean changes in CFQ-R Scores by Group were evaluated between Visit 6 and Visit 1, by Domain.

Time Frame Baseline and Day 42
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Mean change in CFQ-R scores from Visit 1 to Visit 6, by domain.
Arm/Group Title Placebo Low Dose 0.05mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 8 8
Mean (Standard Deviation)
Unit of Measure: mean change of scores on a scale
Physical Domain -5.21  (8.55) -14.58  (17.11) -2.60  (11.34)
Role Domain 0.00  (7.72) -1.04  (5.34) 1.04  (8.26)
Vitality Domain -2.08  (5.89) 4.17  (6.30) 1.04  (20.62)
Emotional Domain -5.83  (12.57) -5.00  (17.73) 4.17  (13.30)
Social Domain -2.08  (9.36) -5.56  (6.64) -4.17  (15.92)
Body Domain 6.94  (14.47) -4.17  (22.17) 8.33  (11.50)
Eating Domain -1.39  (11.01) -1.39  (3.93) -1.39  (3.93)
Treatment Domain 1.39  (9.27) 6.94  (11.79) 5.56  (8.40)
Health Domain 1.39  (9.27) 4.17  (5.75) -4.17  (11.79)
Weight Domain 0.00  (0.00) 12.50  (17.25) -0.00  (17.82)
Respiratory Domain -2.78  (13.61) 2.78  (13.28) -6.94  (22.17)
Digestion Domain -9.72  (12.51) 4.17  (10.18) -5.56  (16.80)
8.Secondary Outcome
Title Change in WBC (White Blood Cell) Count by Group During Treatment Period
Hide Description Safety indices included changes in FEV1 (lung function), changes in WBC, alterations in ECG and sputum microbiology. There were no significant alterations in the ECG in any subjects over the course of the study. There were no subjects who acquired multiple resistant changes in microbiology of sputum and no acquisition of B. cepacia in any subjects. Therefore, these data were not analyzed. The median changes in FEV1 and median changes in WBC, ESR and CRP are reported.
Time Frame Baseline and Day 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety indices included changes in WBC during treatment for each group.
Arm/Group Title Placebo Low Dose 0.05mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 8 8
Median (Inter-Quartile Range)
Unit of Measure: K/cu mm
-510.28
(-2775.00 to 350.92)
-0.98
(-680.00 to 930.00)
-0.13
(-2130.63 to 1.87)
9.Secondary Outcome
Title Changes in C Reactive Protein (CRP) During Treatment.
Hide Description Median changes in CRP and IQR were assessed from serum samples collected at Visits 1,3, 4 and 5.
Time Frame Baseline and Day 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects had blood labs for CRP drawn on Visits 1,3,4 and 5. The changes in median CRP were calculated during the Treatment Period (28 days).
Arm/Group Title Placebo Low Dose 0.05mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 8 8
Median (Inter-Quartile Range)
Unit of Measure: mg/dL
-0.20
(-0.50 to 0.15)
0.05
(0.00 to 0.40)
-0.05
(-0.20 to 0.05)
10.Secondary Outcome
Title Changes in Erythrocyte Sedimentation Rate (ESR) During Treatment Period.
Hide Description Median change in serum ESR (mm/hr) and IQR was calculated from Treatment Period (28 days).
Time Frame Baseline and Day 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects had blood labs for ESR drawn on Visits 1,3,4 and 5. The changes in median ESR were calculated during the Treatment Period (28 days).
Arm/Group Title Placebo Low Dose 0.05mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 8 8
Median (Inter-Quartile Range)
Unit of Measure: mm/hr
-1.00
(-5.50 to 0.50)
3.50
(0.05 to 11.50)
0.00
(-3.50 to 5.00)
11.Secondary Outcome
Title Number of CF Subjects With Microarray Results From Nasal Epithelial Cells to Measure the Effect of Digitoxin on Gene Expression.
Hide Description Rhinoprobe was used to collect nasal epithelial cells. The cells were collected pre and post-treatment and placed in Trizol for RNA isolation then used to measure the effect of digitoxin on gene expression. The full set of microarray data has been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). The accession number for that data is GSE76347 (data available Dec 2018).
Time Frame Day 0 and Day 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full set of microarray data has been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). Results can be found under the accession number GSE76347. One subject's pair of specimens in the placebo group was not collected.
Arm/Group Title All Participants
Hide Arm/Group Description:
All study participants had nasal cells collected pre and post treatment during the study. Because the data set is extremely large, the full set of microarray data has been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) this information can be obtained under the accession number.
Overall Number of Participants Analyzed 23
Measure Type: Number
Unit of Measure: participants
23
12.Secondary Outcome
Title Clinically Significant Alterations in ECG Readings
Hide Description Safety indices included an assessment for the number of clinically significant alterations in the subjects ECG readings from Day 1 to Day 28.
Time Frame 28 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Count of clinically significant alterations in the ECG in all subjects during the Treatment Phase of the study.
Arm/Group Title Placebo Low Dose 0.05mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 8 8
Measure Type: Number
Unit of Measure: participants
0 0 0
13.Secondary Outcome
Title Clinically Significant Changes in the Microbiology of Sputum in Subjects
Hide Description Count of clinically significant changes in sputum microbiology during the Treatment phase (Day 1 to Day 28) to include any new acquisition of B. cepacia or new acquisition of any multiple resistant organism.
Time Frame 28 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
There were no significant changes in the microbiology of sputum in any subjects over the course of treatment.
Arm/Group Title Placebo Low Dose 0.05mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description:

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

Overall Number of Participants Analyzed 8 8 8
Measure Type: Number
Unit of Measure: participants
0 0 0
Time Frame Adverse events were collected from Screening through Day 42 or the Early Withdraw Visit.
Adverse Event Reporting Description Physical exams by study physician at each visit and documented in the subject case report forms. All Adverse Events were subsequently followed up until resolution.
 
Arm/Group Title Placebo Low Dose 0.05 mg Digitoxin Higher Dose 0.1mg Digitoxin
Hide Arm/Group Description

placebo given daily for 28 days

placebo: pill taken once daily for 28 days

low dose 0.05mg digitoxin given once daily for 28 days

digitoxin: 0.05mg tabs, once daily for 28 days

higher dose 0.1mg digitoxin daily for 28 days

digitoxin: 0.1mg pills, once daily for 28 days.

All-Cause Mortality
Placebo Low Dose 0.05 mg Digitoxin Higher Dose 0.1mg Digitoxin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Low Dose 0.05 mg Digitoxin Higher Dose 0.1mg Digitoxin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/8 (0.00%)      0/8 (0.00%)      0/8 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Low Dose 0.05 mg Digitoxin Higher Dose 0.1mg Digitoxin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/8 (87.50%)      5/8 (62.50%)      6/8 (75.00%)    
Gastrointestinal disorders       
abdominal pain * 1  2/8 (25.00%)  4 1/8 (12.50%)  1 1/8 (12.50%)  1
diarrhea * 1  0/8 (0.00%)  0 1/8 (12.50%)  1 1/8 (12.50%)  2
GERD * 1  1/8 (12.50%)  1 1/8 (12.50%)  2 1/8 (12.50%)  1
nausea * 1  2/8 (25.00%)  3 1/8 (12.50%)  1 1/8 (12.50%)  1
General disorders       
fatigue * 1  0/8 (0.00%)  0 1/8 (12.50%)  1 1/8 (12.50%)  2
headache * 1  3/8 (37.50%)  3 4/8 (50.00%)  8 3/8 (37.50%)  3
weight loss  1  0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0
Infections and infestations       
chills * 1  1/8 (12.50%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0
fever * 1  1/8 (12.50%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0
night sweats * 1  1/8 (12.50%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0
sore throat * 1  1/8 (12.50%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0
vaginal yeast infection * 1  0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0
Injury, poisoning and procedural complications       
epistaxis  1  1/8 (12.50%)  1 2/8 (25.00%)  2 0/8 (0.00%)  0
erythema, nares  1  1/8 (12.50%)  1 1/8 (12.50%)  1 0/8 (0.00%)  0
hemoptysis * 1  1/8 (12.50%)  1 1/8 (12.50%)  1 0/8 (0.00%)  0
pain, nares  1  0/8 (0.00%)  0 1/8 (12.50%)  2 0/8 (0.00%)  0
Musculoskeletal and connective tissue disorders       
muscle pain * 1  0/8 (0.00%)  0 4/8 (50.00%)  4 1/8 (12.50%)  1
sprain * 1  0/8 (0.00%)  0 1/8 (12.50%)  1 1/8 (12.50%)  1
Nervous system disorders       
anxiety * 1  0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0
syncope * 1  0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1
tonic clonic seizure  1  1/8 (12.50%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0
Renal and urinary disorders       
increased urination * 1  0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1
urinary tract infection  1  1/8 (12.50%)  1 1/8 (12.50%)  1 0/8 (0.00%)  0
Reproductive system and breast disorders       
menstrual cramps * 1  0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0
upper respiratory infection  1  0/8 (0.00%)  0 0/8 (0.00%)  0 2/8 (25.00%)  2
Respiratory, thoracic and mediastinal disorders       
cough * 1  2/8 (25.00%)  2 2/8 (25.00%)  2 2/8 (25.00%)  2
crackles  1  1/8 (12.50%)  1 1/8 (12.50%)  2 0/8 (0.00%)  0
decrease breath sounds  1  0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0
decreased lung function  1  0/8 (0.00%)  0 1/8 (12.50%)  1 1/8 (12.50%)  1
increased sputum * 1  1/8 (12.50%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0
pulmonary exacerbation  1  2/8 (25.00%)  2 1/8 (12.50%)  1 0/8 (0.00%)  0
rhinitis * 1  2/8 (25.00%)  2 0/8 (0.00%)  0 1/8 (12.50%)  1
rhonchi  1  1/8 (12.50%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0
shortness of breath  1  1/8 (12.50%)  1 1/8 (12.50%)  1 0/8 (0.00%)  0
sinusitis  1  3/8 (37.50%)  3 0/8 (0.00%)  0 0/8 (0.00%)  0
wheeze  1  0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0
Skin and subcutaneous tissue disorders       
rash * 1  0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE v3.0
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.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Pamela L. Zeitlin, M.D., Ph.D., Professor and Director of SOM Pediatric Pulmonary
Organization: Johns Hopkins University
Phone: 443-287-8981
Responsible Party: Pam Zeitlin, National Jewish Health
ClinicalTrials.gov Identifier: NCT00782288     History of Changes
Other Study ID Numbers: FD-R-003456-01
First Submitted: October 29, 2008
First Posted: October 31, 2008
Results First Submitted: October 14, 2015
Results First Posted: January 22, 2016
Last Update Posted: September 14, 2017