A Preliminary Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE) With or Without a Connective Tissue Disorder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 3
- 主要终点
- Change From Baseline in Peak Eosinophil Count
研究概览
简要总结
The purpose of this study is to test the safety and effectiveness of Losartan potassium in subjects with eosinophilic esophagitis (EoE) including those with a connective tissue disorder (CTD) and those without a CTD.
详细描述
The purpose of this research study is to test the safety and effects (good and bad) of Losartan potassium on participants with eosinophilic esophagitis (EoE). If a participant has a connective tissue disorder (CTD) the researchers want to see what effects (good or bad) Losartan has on EoE.
EoE is an inflammatory disease of the esophagus that is typically triggered by exposure to food. Connective tissue disorders (CTDs) are disorders that affect the connective tissues in the body such as tendons and ligaments.
A protein called transforming growth factor (TGF)-beta is associated with both EoE and CTD. Losartan may decrease the amount of TGF-beta and therefore help EoE and CTD.
Losartan is a drug that is approved by the United States Food and Drug Administration (FDA) for use in adults and children over 6 years of age who have high blood pressure. This medication has not been studied in people with EoE.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent/assent
- •Confirmed, active EoE (at Screening or within 12 weeks prior to enrollment)
- •Does or does not have diagnosis of a connective tissue disorder (CTD)
- •Has been on a high dose of proton pump inhibitor (PPI) for at least 8 weeks prior to a diagnostic endoscopy of EoE without histologic resolution (i.e., ≥ 15 eosinophils/HPF).
- •Maintain the same diet, swallowed steroid and PPI therapies throughout the duration of the study
- •Female participants must be either:
- •Of non-childbearing potential (pre-menarchal or surgically sterile with documentation). OR
- •Have a negative urine pregnancy test at screening and at each monthly study visit.
排除标准
- •Any past or planned cardiac surgery.
- •An aortic root Z-score ≥ 3.0 on a previous echocardiogram.
- •Intolerance to Losartan
- •A mean blood pressure measurement (both systolic and diastolic) at screening that is below the 2nd percentile for his/her age
- •Renal dysfunction
- •Another disorder that causes esophageal eosinophilia (e.g., hypereosinophilic syndrome, Churg Strauss vasculitis, eosinophilic granuloma, or a parasitic infection).
- •A diagnosis of hepatic insufficiency (e.g., liver failure, history of liver transplantation or persistent liver transaminase elevation).
- •A history of abnormal gastric or duodenal biopsy or documented gastrointestinal disorders (e.g., Celiac Disease, Crohn's disease or Helicobacter pylori infection), not including chronic gastritis, chronic duodenitis, mucosal eosinophilia or other eosinophilic gastrointestinal disorders (EGIDs).
- •Use of anti-immunoglobulin (Ig)E monoclonal antibody (mAb), anti-tumor necrosis factor (TNF) mAb, anti-IL-5 agents, or anti-IL-13 within 6 months prior to study entry
- •Use of methotrexate, cyclosporine, interferon α, or other systemic immunosuppressive or immunomodulating agents within 3 months prior to the screening visit.
- •A stricture during endoscopy procedure that prevents passage of the endoscope
- •Taking or is planning to take an angiotensin receptor blocker (ARB), angiotensin-converting enzyme inhibitor (ACEI), beta blocker (BB), or calcium-channel blocker therapy at the screening visit or at any time during the study or has been taking any of these medications for 3 months prior to the screening visit.
- •Taking or planning to take hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, rifampin, or fluconazole.
- •Taking or planning to take potassium supplements or salt substitutes containing potassium.
- •A female participant who is pregnant or nursing or, if of childbearing potential, is not using a medically accepted, effective method of birth control (e.g., condom, oral/injectable/subcutaneous contraceptive, intrauterine device, or sexual abstinence).
- •Participated/participating in any investigative drug or device study within 30 days prior to study entry.
- •Participated/participating in any investigative biologics study within 3 months prior to study entry.
- •Unable to be confirmed, active EoE (at Screening or within 12 weeks prior to enrollment)
研究组 & 干预措施
EoE +/- CTD
Participants with EoE with and without CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks
干预措施: Losartan Potassium (Drug)
EoE + CTD
Participants with EoE with CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks
干预措施: Losartan Potassium (Drug)
EoE - CTD
Participants with EoE without CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks
干预措施: Losartan Potassium (Drug)
结局指标
主要结局
Change From Baseline in Peak Eosinophil Count
时间窗: Baseline, 16 weeks
Peak esophageal eosinophil counts were obtained at baseline and 16 weeks. Change in peak eosinophil count is defined as peak count at 16 weeks minus peak count at baseline. A reduction (negative change) in peak count indicates improvement. Peak count is defined as the highest count between the distal and proximal esophageal eosinophil counts.
Number of Serious and Grade 3 or Higher Adverse Events
时间窗: 20 weeks after the start of treatment (16 weeks treatment and 4 weeks follow-up)
The occurrence of serious adverse events and Grade 3 and higher adverse events from Week 0 to Week 20
次要结局
- Percent of Participants in Complete and Partial Histologic Remission at 16 Weeks(16 weeks)
- Change From Baseline in Total Histology Scoring System(Baseline, 16 weeks)
- Change From Baseline in Total Endoscopic Reference Score(Baseline, 16 weeks)
- Change From Baseline in PEESS V2.0(Baseline,16 weeks)
- Change From Baseline in PedsQL EoE(Baseline, 16 weeks)