Losartan as Anti-inflammatory Therapy to Augment F508del Cystic Fibrosis Transmembrane (CFTR) Recovery
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 4
- 主要终点
- Change in Nasal Potential Difference (NPD) to Assess CFTR Activity
研究概览
简要总结
The purpose of the study is to examine if a specific drug called losartan (Cozaar ®), generally used to treat high blood pressure and to protect kidneys from damage in patients suffering from Diabetes Mellitus, will have any effect on the nasal inflammation in patients with cystic fibrosis (CF). The study will be performed at the Pulmonary Division at the University of Miami, Cincinnati Children's Medical Hospital Center, University of Kansas Medical Center and University of Alabama-Birmingham.
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CF patients homozygous for F508del and on current treatment with Orkambi™ for at least 3 months
- •Age >12 years
- •Forced expiratory volume at one second (FEV1) >/= 40% of predicted
排除标准
- •Female patients not willing to adhere to strict birth control (combination of two methods)
- •Pregnancy
- •History of intolerance to angiotensin receptor blockers (ARBs)
- •Treatment with angiotensin converting enzyme (ACE) inhibitor
- •NPD response to zero chloride (0Cl)/isoproterenol of > - 6.6 mV at screening (evidence of detectable CFTR activity at baseline)
- •Regular use of NSAIDs or potassium supplementation, treatment with aliskiren, on anticoagulation
- •Oral corticosteroid use within 6 weeks
- •Exacerbation requiring treatment within 6 weeks
- •Active treatment for mycobacterial infections
- •Significant hypoxemia (oxygen saturation <90% on room air and rest or use of continuous oxygen treatment), chronic respiratory failure by history (pCO2 > 45 mmHg), clinical evidence of cor pulmonale
- •Untreated arterial hypertension (systolic blood pressure >140 mm Hg, diastolic blood pressure > 90 mmHg)
- •Blood pressure less than 90 mm Hg systolic while standing
- •Cardiac, renal (creatinine 1.5 times normal limit), hepatic (LFTs > 3x normal upper limit), neurological, psychiatric, endocrine or neoplastic diseases that are judged to interfere with participation in study
- •Known renal artery stenosis
- •Concomitant airway disorders other than CF, such as allergic bronchopulmonary aspergillosis (ABPA).
- •Subjects with prior thoracic surgery
研究组 & 干预措施
Losartan group
Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).
干预措施: Losartan (Drug)
Placebo group
Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
干预措施: placebo (Drug)
结局指标
主要结局
Change in Nasal Potential Difference (NPD) to Assess CFTR Activity
时间窗: Baseline, 12 weeks
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activity will be measured as the change in NPD in response to apical perfusion with 0 Cl-/isoproterenol. NPD will be measured at the nasal epithelium via a voltmeter.
次要结局
- Change in GM-CSF Values(Baseline, 12 weeks)
- Change in NPD to Assess BK Activity(Baseline, 12 weeks)
- Change in Sweat Chloride Concentration(Baseline, 12 weeks)
- Change in Quality of Life (QoL) Scores as Assessed by the CFQ-R(Baseline, 12 weeks)
- Change in hsCRP(Baseline, 12 weeks)
- Change in Losartan Metabolites Levels(Baseline, 12 weeks)
- Change in NPD to Assess CaCC Activity(Baseline, 12 weeks)
- Change in Blood Count Values(Baseline, 12 weeks)
- Change in %PMN Values(Baseline, 12 weeks)
- Change in SAA Values(Baseline, 12 weeks)
- Change in Calprotectin Values(Baseline, 12 weeks)
- Change in TGF-beta Values(Baseline, 12 weeks)
- Change in mRNA Expression(Baseline, 12 weeks)
- Change in FEV1(Baseline, 12 weeks)
- Change in Cytokine Levels(Baseline, 12 weeks)
研究者
Matthias Salathe
Emeritus Professor
University of Miami