Hepatic Encephalopathy MedDRA version: 14.1 Level: PT Classification code 10019660 Term: Hepatic encephalopathy System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Hepa-Merz® Granulat 3000
Product Name: Hepa-Merz® Granulat 3000
Pharmaceutical Form: Granules for oral solution
INN or Proposed INN: L-ornit
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with established cirrhosis and previously documented minimal hepatic encephalopathy, either untreated or treated with standard of care, lactulose. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 34 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Current excess alcohol use or within 1 month, 2. Recent use of psychiatric medication within 1 month 3. Affective disorder 4. Severe coagulopathy (INR greater than 2, platelet count less than 60,000) 5. Known myopathy or myositis 6. Trauma to the lower extremities within 3 months 7. Recent intestinal haemorrhage within 1 month 8. Ferromagnetic implant or foreign body 9. Claustophobia or previous inability to tolerate MRI scanning. 10. Age over 65
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: Improvement in mental state by paper-and-pencil-based Psychometric Hepatic Encephalopathy Score (PHES) and Cogstate Research test(computer-based cognitive assessment research tool) ; Secondary Objective: 1. Brain volume reduction (reduction in brain swelling) measured by magnetic resonance imaging (MRI) of the brain and improvement in the chemical structure of the brain (cerebral osmolytes) measured by in vivo MR spectroscopy (MRS) scanning of the brain 2. Improvement in brain function through assessment of key areas of the brain involved in attention and memory (the default mode network [DMN] measured by functional MRI of the Brain (fMRI) 3. Improvement in muscle function (muscle metabolome normalisation) and increase muscle size (fat free mass), measured by in vivo MRS scanning and MR imaging scans of the leg and by vitro NMR spectroscopy, mass spectroscopy, histology on muscle biopsy samples. 4. Improvement in the profile of key chemicals in the blood and urine (plasma and urinary metabolome), measured with in vitro NMR spectroscopy to assess for biomarkers of treatment response and to determine the amino acids changed in hepatic encephalopathy. ;Primary end point(s): Improvement in mental state of patients with hepatic encephalopathy measured by paper-and-pencil-based Psychometric Hepatic Encephalopathy Score (PHES) and Cogstate Research computer-based psychometric battery after 12 weeks treatment with L-ornithine L-aspartate;Timepoint(s) of evaluation of this end point: After 12 weeks of treatment with L-ornithine L-aspartate | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Detection of small changes in brain size following alterations in degree of encephalopathy in patients during and after LOLA administration using in vivo T1-weighted magnetic resonance imaging (MRI). 2. Detection of improvement in cerebral osmolytes (creatinine, choline, N-acetylaspartate, myoinosotol, glutamine/glutamate, lactate) in patients during and after LOLA administration using in vivo 1H MR spectroscopy (MRS). 3. Detection of improvement in brain function in patients during and after LOLA administration through assessment of the default mode network (DMN) on functional MRI of the brain (fMRI). 4. Detection of improvement in health-related quality of life (HRQoL) as measured by CLDQ and SF-36 in patients during and after LOLA administration. 5. Detection of normalisation of the muscle metabolome, function (detected by in vitro NMR spectroscopy, and mass spectroscopy), mass (detected by in vivo imaging of muscle) and increase in fat free histology on muscle biopsy samples can be measured in patients during and after LOLA administration. 6. Correlation of the histological, NMR spectroscopic and energetic functions of muscle with the ammonia levels and degree of hepatic encephalopathy. 7. Improvement in the plasma and urinary metabolome (measured with in vitro NMR spectroscopy) for biomarkers of response and amino acids changed in hepatic encephalopathy in patients during and after LOLA therapy. ;Timepoint(s) of evaluation of this end point: After 12 weeks of treatment with L-ornithine L-aspartate | — |
Countries
United Kingdom
Contacts
Public ContactProfessor Simon Taylor-Robinson
Imperial College London
Outcome results
None listed