Evaluation of Intestinal Permeability in Cirrhotic Patients Before and After Treatment With Non-selective Beta Blocker (Propranolol)
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Intestinal permeability
研究概览
简要总结
This study seeks to investigate whether non-selective beta blocker treatment decreases intestinal permeability in cirrhotic patients by altering the expression of genes encoding intercellular junction proteins.
详细描述
There is evidence that the non-selective beta-blocker (NSBB) propranolol reduces intestinal permeability and decreases bacterial translocation in cirrhotic patients, independent of hemodynamic effects on portal pressure. The mechanism by which this decrease in intestinal permeability and bacterial translocation occurs has not been established. Among the proposed mechanisms are: modification of splanchnic hemodynamics, increased gastrointestinal motility, and immunological properties of nonselective beta blockade. It is not known, however, if beta-blocker treatment decreases intestinal permeability by altering the expression of genes encoding intercellular junction proteins. This study seeks to investigate this question to improve understanding of the mechanism by which beta-blockers work in primary and secondary prophylaxis of variceal hemorrhage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •> 18 years
- •Diagnosis of cirrhosis of any etiology or severity as established by the treating physician (biopsy, biochemical, imaging)
- •High risk gastroesophageal varices, that is those with medium/large varices or any size varices with red wale signs
- •Scheduled appointment for endoscopic ligation as previously ordered by the treating physician
- •Signed informed consent
- •Ability to keep return appointments
排除标准
- •Beta blocker treatment within 1 month prior to study period
- •Antibiotic treatment during or within 1 month prior to study period
- •Prebiotic or probiotic treatment during or within 1 month before study period
- •Current immunosuppressive treatment
- •Patients with active infectious process
- •Patients with portal thrombosis
- •Patients with hepatocellular carcinoma
- •Patients with intestinal surgical shunts
- •Patients with chronic diarrhea or documented celiac disease
- •Patients with chronic renal failure (KDOQI: ≤ 3)
- •Patients with allergy or absolute contraindication for the use of nonselective beta blockers (asthma, significant heart block, systolic BP <90 mm Hg, basal HR <55, refractory ascites)
研究组 & 干预措施
Propanolol
Patients will take the non-selective beta blocker propranolol for approximately 4 weeks starting immediately after endoscopy for esophageal variceal ligation. Patients will be initiated on a dose of 20mg by mouth every 12 hrs before titration to maximum tolerated dose. Patients will undergo testing before and after treatment for the variables listed in the outcomes section below.
干预措施: Propanolol (Drug)
结局指标
主要结局
Intestinal permeability
时间窗: Baseline and after 4 weeks of propranolol treatment
Evaluate and compare intestinal permeability using studies evaluating the absorption of three orally administered sugars (sucrose, mannitol and lactulose) in patients with cirrhosis before and after treatment with propranolol for 1 month.
次要结局
- Presence of intercellular junction proteins by immunohistochemistry(Baseline and after 4 weeks of propranolol treatment)
- Expression of genes related to intestinal mucosal integrity(Baseline and after 4 weeks of propranolol treatment)
- Serum inflammatory markers(Baseline and after 4 weeks of propranolol treatment)
研究者
ALDO TORRE DELGADILLO
MD
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran