NCT01847651

Brain Muscle Axis During Treatment of Hepatic Encephalopathy With L-ornithine L-aspartate

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

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 42 (actual)
• Sponsor: Imperial College London · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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 1\) 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 1. 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. 2. Improvement in brain function 3. 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. 4. Improvement in the chemical profile of key chemicals in the blood and urine, measured with in vitro NMR spectroscopy

Conditions

• Hepatic Encephalopathy
• Minimal Hepatic Encephalopathy
• Cirrhosis

Interventions

Type	Name	Description
PROCEDURE	Vastus Muscle Biopsy	Both Arms, all 3 visits at 0, 4 and 12 weeks
DRUG	LOLA or placebo	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)for 12 weeks
OTHER	Cognitive assessment (PHES)	Both Arms, all 3 visits at 0, 4 and 12 weeks
OTHER	Cognitive Assessement (Cogstate)	Both Arms, all 3 visits at 0, 4 and 12 weeks
OTHER	blood and urine sampling	Both Arms, all 3 visits at 0, 4 and 12 weeks
OTHER	Nutritional assessment	Both Arms, all 3 visits at 0, 4 and 12 weeks
OTHER	MRI brain and spectroscopy	Both Arms, all 3 visits at 0, 4 and 12 weeks
OTHER	MRI leg cross section	Both Arms, all 3 visits at 0, 4 and 12 weeks
OTHER	Functional MRI (working memory and attention tasks)	Both Arms, all 3 visits at 0, 4 and 12 weeks

Timeline

• Start date: 2013-08-01
• Primary completion: 2015-06-01
• Completion: 2015-06-01
• First posted: 2013-05-07
• Last updated: 2015-10-22

Locations

1 site across 1 country: United Kingdom