Randomized, Controlled Trial of S-adenosylmethionine in Alcoholic Liver Disease (RCT SAMe)
2010年9月9日 更新者:Loma Linda University
Effect of Oral S-Adenosylmethionine Administration on Abnormalities of Hepatic Methionine Metabolism and Disease Progression in Alcoholic Liver Disease. A Randomized, Double Blind, Placebo-controlled Trial
Background: Alcoholic liver disease is one of the most important causes of chronic liver disease in this country.
There is currently no treatment for chronic alcoholic liver disease other than abstinence.
Hepatic methionine metabolism is abnormal in these patients and one of the consequences is depletion of S-adenosylmethionine (SAMe) levels, which can affect numerous important cellular processes.
SAMe has been increasingly utilized for the treatment of liver diseases although the protective mechanisms remain unclear.
A recent randomized double-blind trial using SAMe in patients with alcoholic liver disease and found improvement in 2-year survival in those with less advanced liver disease.
However, important changes in methionine metabolism and histological changes were not included in the study.
Aim: The goal of this study is to determine the effect of SAMe administration on key metabolic abnormalities of the methionine cycle and on the recovery from alcoholic liver disease.
研究概览
详细说明
Methods: This is a randomized, double blind, placebo-controlled trial.
Thirty patients with stable alcoholic hepatitis (Maddrey Score < 32) without cirrhosis who meet entry criteria will receive either 400 mg of SAMe (n=15) or placebo (n=15) three times a day for the duration of one year.
History, physical assessment, various blood tests and a liver biopsy will be performed prior to treatment.
Patients will have repeat blood tests on subsequent follow-up visits every month for the first two months, then every two months thereafter.
They will also be encouraged to abstain from alcohol during these visits.
A post-treatment liver biopsy will be obtained at the end of the trial.
The primary outcome parameters include serum homocysteine, SAMe and TNFalpha levels, and the expression of key hepatic enzymes of the methionine cycle and of hepatic SAMe and glutathione levels.
Histological progression of alcoholic liver disease, clinical and biochemical indices of liver disease, and quality of life assessment will also be examined.
研究类型
介入性
注册 (预期的)
60
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
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California
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Loma Linda、California、美国、92354
- Loma Linda University
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Patients must be chronic alcohol users, defined by a history of ethanol consumption on average > 40g/day for women and 60g/day for men for at least 1 year before inclusion.
- The presumptive diagnosis for alcoholic hepatitis will be: recent binge drinking; compatible physical findings (one or more: jaundice, enlarged liver, hepatic bruit, abdominal pain, loss of appetite, nausea); and a compatible biochemical profile (moderate elevation of AST over ALT, elevated total serum bilirubin); or a liver-spleen colloid scan suggestive of reticulo-endothelial redistribution and hepatic arterialization.
- The diagnosis of alcoholic hepatitis must be confirmed on liver biopsy, showing typical features of acute sclerosing hyaline necrosis 70.
- The degree of portal fibrosis as determined on liver biopsy, graded according to the Knodell score-modified by Ishak 71 must be less than or equal to 5 out of a possible score of 6, 6 indicating cirrhosis.
- The alcoholic hepatitis must be "stable", i.e. not requiring treatment by either pentoxifylline 72 or prednisone, with a Maddrey Score 73 {(PTpatient - PTcontrol) x 4.6 + TBmg/dL} < 32.
- Patients must be willing to participate in the trial, remain abstinent to alcohol, and compliant to the treatment regimen, and undergo a post-treatment liver biopsy.
Exclusion Criteria:
- Patients who have either compensated cirrhosis (biopsy proven) or a clinical picture of severe cirrhosis defined as Child's class C and/or with a recent history (within one month) of decompensated liver disease (history of ascites, encephalopathy or variceal bleeding within one month of trial entry). These patients have reduced life expectancy below one year and are most often severely coagulopathic and cannot be biopsied.
- Patients who have severe acute alcoholic hepatitis of poor prognosis defined as a Maddrey Score > 32. These patients have a mortality rate of 50% during their hospitalization period when untreated by either prednisone or pentoxifylline.
- Patients who are receiving hepatotropic treatments such as colchicine, penicillamine, corticosteroids, ursodeoxycholic acid, and pentoxifylline.
- Patients who are receiving known hepatotoxic long-term treatments such as NSAIDs, statins, neuroleptics, certain anti-convulsive medications, or high-dose acetaminophen.
- Patients suspected of having hepatocellular carcinoma.
- Patients who have contra-indications to liver biopsy.
- Patients who have a liver biopsy that does not yield sufficient specimen for analyses.
- Patients who have untreated deficiencies of folic acid, vitamin B6 or B12.
- Patients who have chronic active Hepatitis B or C, hemochromatosis, autoimmune hepatitis, or a cholangiopathy.
- Patients with psychotic disorders, and in particular manic depression (contra indication to SAMe treatment).
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:三倍
武器和干预
参与者组/臂 |
干预/治疗 |
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安慰剂比较:1个
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TID
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有源比较器:SAMe
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300 mg TID
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Change in plasma homocysteine, hepatic GSH and SAMe levels and hepatic expression of TNF,MAT1A,MAT2A,MS,CBS and BHMT.
大体时间:1 year
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1 year
|
次要结果测量
结果测量 |
大体时间 |
---|---|
Changes in routine liver pathology,c-myc expression and markers of apoptosis, stellate cell activation and hepatocyte proliferation.
大体时间:1 year
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1 year
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员:Michel H Mendler, M.D.、Loma Linda Univeristy
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2008年10月1日
初级完成 (实际的)
2010年5月1日
研究完成 (实际的)
2010年5月1日
研究注册日期
首次提交
2009年2月24日
首先提交符合 QC 标准的
2009年2月24日
首次发布 (估计)
2009年2月26日
研究记录更新
最后更新发布 (估计)
2010年9月13日
上次提交的符合 QC 标准的更新
2010年9月9日
最后验证
2010年9月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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Mila (bMotion Technologies)完全的
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Universidad Autonoma de MadridCentro Universitario La Salle完全的