LOLA in Hepatic Encephalopathy Brain Muscle Axis During Treatment of Hepatic Encephalopathy With L-ornithine L-aspartate A Phase iv Randomised Double Blind Placebo- Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Improvement in mental state on paper and pencil Hepatic Encephalopathy score (PHES) testing and Cogstate testing (computer based cognitive assessment research tool)
研究概览
简要总结
Patients with cirrhosis of the liver may suffer from a condition called hepatic encephalopathy which in its mildest form as mental slowing and impaired reaction times in driving and machinery operation. Left untreated it may lead to deep coma. The cause is not fully understood but is though to be related to the inability of a damaged liver to filter out toxins such as ammonia in the blood, which then accumulate within the brain and result in altered function and swelling within certain brain cells,astrocytes. These patients also suffer from muscle loss, which is associated with a poor outcome. L-ornithine L-aspartate(LOLA) is a licensed drug in Germany and has been shown to promote ammonia elimination from the body in the form of urea. Some experimental studies have suggested that LOLA also potentially attenuates muscle loss by incorporating ammonia into muscle in the form of glutamine. The aim of this study is to determine cognitive and nutritional effects of 12 weeks of LOLA administration and its effect on brain muscle structure and function in patients with cirrhosis.
详细描述
This is a Phase IV randomised double blind, placebo controlled study. Thirty four patients with cirrhosis will be studied with psychometric tests, clinical brain magnetic resonance imaging(MRI),including functional MRI) and magnetic resonance spectroscopy (MRS) and muscle MRI of leg muscle before (time 0)during (4weeks)and after LOLA or placebo treatment at 12 weeks. Samples will also be taken for ex vivo MRS of blood and urine to identify potential biomarkers. Histological analysis and MRS would also be performed on the muscle tissue at the same time points.
Hypotheses Primary objective
- Improvement in mental state by paper and pencil based Psychometric Hepatic Encephalopathy Score (PHES) and Cogstate Research test (computer based cognitive research assessment tool)
Secondary objectives
- Brain volume reduction due to reduction in brain swelling measured by MRI and improvement in the chemical structure of the brain due to (cerebral osmolytes)measured by in vivo MR Spectroscopy (MRS)scanning of the brain.
- Improvement in brain function
- Improvement in muscle function (muscle metabolome normalisation) and increased muscle size (fat free mass), measured in vivo by MRI scanning and by in vitro mass spectroscopy and NMR spectroscopy and histological analysis of muscle samples.
- Improvement in the chemical profile of key chemicals in the blood and urine, measured with in vitro NMR spectroscopy
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Ambulant patients of any Child-Pugh stage cirrhosi and PHEs defined MHe or grade 1 encephalopathy
排除标准
- •Previous episodes of overt HE without a clear precipitant
- •Recurrent excessive alcohol consumption (abstinence for those with alcoholic liver disease otherwise less than 28 units per week)
- •Severe coagulopathy (INR>2, platelets <60 000/uL, Fibrinogen <1mg/dl)
- •known myopathy or myositis, taruma to lower extremities within 3 months)
- •Renal dysfunction with a serum creatinine>3mg/dl (265micromol/L)
- •Ferromagnetic implants
- •Recent intestinal haemorrhage within 1 month
- •Claustrophobia
- •Weight >120kg
- •Major psychoactive medication such as antipsychotic agents
- •Known cerebrovascular disease or pre-existing neurological conditions
- •Age less than 18 or greater than 65.
研究组 & 干预措施
LOLA
Other Names:
Hepa-Merz Granulat 3000 Hepa-Merz granules 3g (Each 5g sachet contains 3g of L-ornithine L-aspartate) L-ornithine L-aspartate LOLA
Randomised to a daily dose 18g per day, two sachets of Hepa-Merz granules three times a day (or placebo)
干预措施: Nutritional assessment (Other)
LOLA
Other Names:
Hepa-Merz Granulat 3000 Hepa-Merz granules 3g (Each 5g sachet contains 3g of L-ornithine L-aspartate) L-ornithine L-aspartate LOLA
Randomised to a daily dose 18g per day, two sachets of Hepa-Merz granules three times a day (or placebo)
干预措施: Vastus Muscle Biopsy (Procedure)
LOLA
Other Names:
Hepa-Merz Granulat 3000 Hepa-Merz granules 3g (Each 5g sachet contains 3g of L-ornithine L-aspartate) L-ornithine L-aspartate LOLA
Randomised to a daily dose 18g per day, two sachets of Hepa-Merz granules three times a day (or placebo)
干预措施: LOLA or placebo (Drug)
LOLA
Other Names:
Hepa-Merz Granulat 3000 Hepa-Merz granules 3g (Each 5g sachet contains 3g of L-ornithine L-aspartate) L-ornithine L-aspartate LOLA
Randomised to a daily dose 18g per day, two sachets of Hepa-Merz granules three times a day (or placebo)
干预措施: Cognitive assessment (PHES) (Other)
LOLA
Other Names:
Hepa-Merz Granulat 3000 Hepa-Merz granules 3g (Each 5g sachet contains 3g of L-ornithine L-aspartate) L-ornithine L-aspartate LOLA
Randomised to a daily dose 18g per day, two sachets of Hepa-Merz granules three times a day (or placebo)
干预措施: Cognitive Assessement (Cogstate) (Other)
LOLA
Other Names:
Hepa-Merz Granulat 3000 Hepa-Merz granules 3g (Each 5g sachet contains 3g of L-ornithine L-aspartate) L-ornithine L-aspartate LOLA
Randomised to a daily dose 18g per day, two sachets of Hepa-Merz granules three times a day (or placebo)
干预措施: blood and urine sampling (Other)
LOLA
Other Names:
Hepa-Merz Granulat 3000 Hepa-Merz granules 3g (Each 5g sachet contains 3g of L-ornithine L-aspartate) L-ornithine L-aspartate LOLA
Randomised to a daily dose 18g per day, two sachets of Hepa-Merz granules three times a day (or placebo)
干预措施: MRI brain and spectroscopy (Other)
LOLA
Other Names:
Hepa-Merz Granulat 3000 Hepa-Merz granules 3g (Each 5g sachet contains 3g of L-ornithine L-aspartate) L-ornithine L-aspartate LOLA
Randomised to a daily dose 18g per day, two sachets of Hepa-Merz granules three times a day (or placebo)
干预措施: MRI leg cross section (Other)
LOLA
Other Names:
Hepa-Merz Granulat 3000 Hepa-Merz granules 3g (Each 5g sachet contains 3g of L-ornithine L-aspartate) L-ornithine L-aspartate LOLA
Randomised to a daily dose 18g per day, two sachets of Hepa-Merz granules three times a day (or placebo)
干预措施: Functional MRI (working memory and attention tasks) (Other)
Placebo
干预措施: Vastus Muscle Biopsy (Procedure)
Placebo
干预措施: LOLA or placebo (Drug)
Placebo
干预措施: Cognitive assessment (PHES) (Other)
Placebo
干预措施: Cognitive Assessement (Cogstate) (Other)
Placebo
干预措施: blood and urine sampling (Other)
Placebo
干预措施: Nutritional assessment (Other)
Placebo
干预措施: MRI brain and spectroscopy (Other)
Placebo
干预措施: MRI leg cross section (Other)
Placebo
干预措施: Functional MRI (working memory and attention tasks) (Other)
结局指标
主要结局
Improvement in mental state on paper and pencil Hepatic Encephalopathy score (PHES) testing and Cogstate testing (computer based cognitive assessment research tool)
时间窗: At 0, 4 and 12 weeks
次要结局
- Brain Volume(At 0 , 4 and 12 weeks)
- Brain chemical structure(0, 4, 12 weeks)
- Improvement in brain function measured by functional MRI(0, 4, 12 weeks)
- Improvement in Muscle Function and increase in muscle size(0, 4 and 12 weeks)
- Improvement of plasma and urine metabolome(0, 4 and 12 weeks)