A Phase 4 interventional study of Vastus Muscle Biopsy and LOLA or placebo in Hepatic Encephalopathy, Minimal Hepatic Encephalopathy and Cirrhosis, sponsored by Imperial College London. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2015-10-22.
Sponsored by Imperial College London · Phase 4, Interventional, and Treatment
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.
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
222 studies on the registry are indexed under Hepatic Encephalopathy; 49 are open to participants now.
This study's enrollment of 42 is below the median of 60 across 151 interventional studies indexed under Hepatic Encephalopathy.
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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)
Procedure: Vastus Muscle Biopsy · Drug: LOLA or placebo · Other: Cognitive assessment (PHES) · Other: Cognitive Assessement (Cogstate) · Other: blood and urine sampling · Other: Nutritional assessment · Other: MRI brain and spectroscopy · Other: MRI leg cross section · Other: Functional MRI (working memory and attention tasks)
Procedure: Vastus Muscle Biopsy · Drug: LOLA or placebo · Other: Cognitive assessment (PHES) · Other: Cognitive Assessement (Cogstate) · Other: blood and urine sampling · Other: Nutritional assessment · Other: MRI brain and spectroscopy · Other: MRI leg cross section · Other: Functional MRI (working memory and attention tasks)
Both Arms, all 3 visits at 0, 4 and 12 weeks
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
Both Arms, all 3 visits at 0, 4 and 12 weeks
Both Arms, all 3 visits at 0, 4 and 12 weeks
Both Arms, all 3 visits at 0, 4 and 12 weeks
Both Arms, all 3 visits at 0, 4 and 12 weeks
Both Arms, all 3 visits at 0, 4 and 12 weeks
Both Arms, all 3 visits at 0, 4 and 12 weeks
Both Arms, all 3 visits at 0, 4 and 12 weeks
Improvement in mental state on paper and pencil Hepatic Encephalopathy score (PHES) testing and Cogstate testing (computer based cognitive assessment research tool)
Time frame: At 0, 4 and 12 weeks
Brain Volume
The effect of brain volume reduction due to reduction of brain swelling will be measured by serial brain MRI (at 0, 4 and 12 weeks)
Time frame: At 0 , 4 and 12 weeks
Brain chemical structure
Improvement in brain chemical structure (by measuring cerebral osmolytes) will be assessed by in-vivo MR spectroscopy
Time frame: 0, 4, 12 weeks
Improvement in brain function measured by functional MRI
Key brain functions such as attention and working memory (the default mode network) will be assessed through fMRI
Time frame: 0, 4, 12 weeks
Improvement in Muscle Function and increase in muscle size
Increase in muscle size(fat free mass) will be measured on by MR imaging of the thigh, in-vitro NMR spectroscopy, mass spectroscopy and histological analysis of muscle biopsy samples.
Time frame: 0, 4 and 12 weeks
Improvement of plasma and urine metabolome
Improvement in blood and urine profiles will be measured with in vitro NMR spectroscopy to assess for biomarkers of treatment response and to determine the amino acids altered by treatment of HE.
Time frame: 0, 4 and 12 weeks
The record gives a start of Aug 2013, a primary completion of Jun 2015 and a completion of Jun 2015. It does not say whether these dates are actual or estimated.
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This study is completed, as verified in May 2013. You cannot join it, but the record below documents what was studied.
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