LOLA in Hepatic Encephalopathy

• Research type

  Research Study

• Full title

  Brain muscle axis during treatment of hepatic encephalopathy with L-ornithine L-aspartate

• IRAS ID

  113951

• Contact name

  Simon Taylor-Robinson

• Sponsor organisation

  Imperial College London and Imperial College Healthcare NHS Trust

• Eudract number

  2012-003817-32

• Research summary

  Patients with cirrhosis may suffer from a condition called hepatic encephalopathy which manifests in its mildest form as mental slowing and impaired reaction times in driving and operating machinery, and may lead untreated to deep coma in some individuals. The cause is not fully understood, but it is thought to be related to an inability of the damaged liver to filter out toxins in the blood, such as ammonia, which then accumulate in the brain and causes altered function and varying degrees of brain swelling. These patients also suffer from muscle loss, which is associated with poor outcome. L-ornithine L-aspartate (LOLA) is a licenced drug in Germany for many years and has been shown to kick-start the liver to eliminate ammonia in the form of urea. Experimental studies have suggested that it also promotes the incorporation of ammonia into muscle in the form of glutamine, thereby potentially reducing muscle loss. The aim of the study is to determine the cognitive and nutritional effects of 12 weeks of LOLA administration and its effect on brain and muscle structure and function in patients with cirrhosis. 34 patients will be studied with psychometric tests, clinical brain MRI (including functional MRI and magnetic resonance spectroscopy [MRS]) and muscle MRI (of the leg muscles) before (time 0), during (time 4 weeks) and after LOLA treatment or placebo (time 12 weeks). Samples will also be taken for MRS of blood and urine for development of new disease biomarkers. A muscle biopsy for both histology and MRS to determine the physiological effects of treatment on brain and muscle structure and function will also be taken at each of the three time points.

• REC name

  London - Fulham Research Ethics Committee

• REC reference

  12/LO/1937

• Date of REC Opinion

  7 Jan 2013

• REC opinion

  Further Information Favourable Opinion