The Role of Ursodeoxycholic Acid in Treatment of Gallstones in Hemolytic Disorders
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Lack of sonographic, clinical or biochemical evidence of progression of cholelithiasis or biliary sludge.
研究概览
简要总结
It is well established that hemolytic diseases predispose patients to the development of pigment gallstones. Gallstones are noted in at least 5% of children under the age of 10 years, increasing to 40-50% in the second to fifth decades. The co-inheritance of Gilbert's syndrome increases the risk of cholelithiasis four to five-fold.
In patients with chronic hemolysis, total bile lipid concentration is decreased and the total bilirubin to total lipid ratio is increased. This suggests that the conjugating capacity of hepatocytes is surpassed by the excessive amount of bilirubin resulting from hemolysis. Increased bilirubin monoconjugate and unconjugated bilirubin can precipitate in bile and form complexes with inorganic ions, mostly calcium, and develop into stones.
Patients with hemolytic disorders can also develop biliary sludge, a suspension of precipitated particulate matter in bile dispersed in a viscous, mucin-rich liquid phase . The chemical composition of the precipitates correlates well with the composition of the associated stone and sludge often stands as a harbinger of future stone development.
There is strong data suggesting a benefit in treating cholelithiasis with UDCA and also in preventing gallstone development in various high risk scenarios.
There are several proposed mechanisms for the positive effect of UDCA in primary prevention of pigment stones. Mucoglycoproteins are present in significant amounts in black pigment stones and contribute to the matrix of gallstones. UDCA suppresses the secretion of protein and decreases the levels of various proteins in bile . It has also been suggested that increased colonic bile salt may solubilize unconjugated bilirubin and may prevent calcium complexing.
There is no published data at present on the role of UDCA in prevention and treatment of cholelithiasis in hemolytic diseases. The investigators hypothesise that UDCA can be of benefit to patients with hemolytic disorders in the primary prevention of pigment stones, possible resolution of biliary sludge and existent stones, and reduction of symptomatic episodes of cholelithiasis.
详细描述
The research protocol extends for up to 12 months, during which the participant will attend 3 clinic visits at Shaare Zedek Medical Centre; one at study enrollment, one at 6 months and one at 12 months.
All patients identified will have their medical records reviewed for previous clinical, biochemical or sonographic evidence of gallstones.
Patients will undergo a baseline abdominal ultrasound to assess for biliary sludge, gallstones, or evidence of previous cholecystitis (eg. Thickened gallbladder wall).
All patients will also have blood tested for liver biochemistry, complete blood count, hemolytic screen and fasting lipids.
Participants will be commenced on UDCA 15mg/kg/day (maximum dose 900mg/day) in 2-3 divided doses for 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of a hemolytic disorder including spherocytosis, G6PD deficiency, thalassemia or sickle cell disease.
- •Patients with cholelithiasis or bile sludge.
- •Age greater than or equal to 4 years.
- •Ability to consent to and participate in the study and follow study procedures.
排除标准
- •Previous splenectomy (complete or partial)
- •Evidence of hemolytic crisis at the time of research enrollment
- •Patients with highly symptomatic gallstones who have planned surgical intervention
- •Known allergy or intolerance to UDCA
- •Existence of concurrent hepatic disease
- •Any other laboratory or clinical condition that the investigator considers clinically significant that could impact the outcome of the study or the safety of the patient.
研究组 & 干预措施
Open Label
32 patients with hemolytic disorders meeting the inclusion and exclusion criteria will be commenced on Ursodeoxycholic acid (UDCA).
干预措施: Ursodeoxycholic Acid (Drug)
结局指标
主要结局
Lack of sonographic, clinical or biochemical evidence of progression of cholelithiasis or biliary sludge.
时间窗: 12 months
次要结局
- Sonographic improvement (size and number of gallstones, presence of bile sludge, gallbladder wall thickness).(12 months)
- Improvement in number and severity of episodes of symptomatic gallstones.(12 months)
- Rate of surgical intervention for gallstones disease.(12 months)
- Evaluate tolerability and adverse effects of UDCA therapy in hemolytic disorders.(12 months)
- Improved biochemical evidence of gallstone disease(12m)