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

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.

Conditions

• Hepatic Encephalopathy
• Minimal Hepatic Encephalopathy
• Cirrhosis

Interventions

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

Sponsors & Collaborators

• Imperial College London

  lead OTHER

Principal Investigators

• Simon D Taylor-Robinson, MD FRCP · Imperial College London

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-08-31

Primary Completion

2015-06-30

Completion

2015-06-30

Countries

• United Kingdom

Study Locations