Phase II Study of Digitoxin to Treat Cystic Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients.
研究概览
简要总结
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
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •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
- •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.
研究组 & 干预措施
1
low dose 0.05mg digitoxin given once daily for 28 days
干预措施: digitoxin (Drug)
2
higher dose 0.1mg digitoxin daily for 28 days
干预措施: digitoxin (Drug)
3
placebo given daily for 28 days
干预措施: placebo (Other)
结局指标
主要结局
Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients.
时间窗: 42 days (Day 1 to Day 42)
The Il-8 measurements of sputum digitoxin levels for each group is shown for 5 days (Days 1, 14, 21, 28 and 42).
Change in Il-8 (Interleukin 8) Levels From Day 28 Minus Day 1 (Treatment Period).
时间窗: 28 days (Day 28 minus Day 1)
Change in Il-8 values are expressed as a change in log 10 Il-8 pg/mL from Day 28 minus Day 1.
Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients.
时间窗: 42 days (Day 1- Day 42)
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).
Change in Neutrophil Cell Count Day 28 Minus Day 1 (Treatment Period).
时间窗: 28 days (Day 28 minus Day 1)
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).
次要结局
- 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)
- Changes in C Reactive Protein (CRP) During Treatment.(Baseline and Day 28)
- Change in WBC (White Blood Cell) Count by Group During Treatment Period(Baseline and Day 28)
- Changes in Erythrocyte Sedimentation Rate (ESR) During Treatment Period.(Baseline and Day 28)
- Number of CF Subjects With Microarray Results From Nasal Epithelial Cells to Measure the Effect of Digitoxin on Gene Expression.(Day 0 and Day 28)
- Clinically Significant Alterations in ECG Readings(28 days)
- Clinically Significant Changes in the Microbiology of Sputum in Subjects(28 days)
研究者
Pam Zeitlin
Professor of Pediatrics
National Jewish Health