Hepatic EncephalopathyPhase 4NCT01041755
Efficacy of L-Ornithine L-Aspartate in Acute Hepatic Encephalopathy.
A Phase 4 study testing L-ornithine-L-aspartate and Lactose in people with Hepatic Encephalopathy, run by Centro Regional para el Estudio de las Enfermedades Digestivas at 1 site in Mexico.
Trial summary
Hepatic encephalopathy is caused by the effects on the brain of substances that under normal circumstances are efficiently metabolized in the liver. The hyperammonemia is the main factor responsible for the development of hepatic encephalopathy. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatic Encephalopathy
- What is being tested?
- L-ornithine-L-aspartate and Lactose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteMexico
- Study dates
- Nov 2009to Jun 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with cirrhosis of any etiology, diagnosed by ultrasound,clinical and / or histologic criteria
- Patients over 18 years and under 75
- Patients with hepatic encephalopathy grade 3-4 according to the criteria of West Haven
- Patients with hyperammonemia >10 µmol/l
Who cannot join
- Evidence of neurological or psychiatric illness
- Use of drugs affecting the central nervous system
- Withdrawal Syndrome
- Anorectal disease that interferes with the administration of enemas
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Hospital Universitario "José Eleuterio González"
Monterrey, Nuevo León, 64460
About this study
Official title: The Infusion of L-Ornithine L-aspart is as Effective as Nonabsorbable Disaccharides in the Management of Acute Hepatic Encephalopathy.
Hepatic encephalopathy is caused by the effects on the brain of substances that under normal circumstances are efficiently metabolized in the liver. The hyperammonemia is the main factor responsible for the development of hepatic encephalopathy. In patients with cirrhosis, the reduction in hepatocellular function and generation of portosystemic shunts contribute to increase serum ammonium. The current therapeutic approaches, are aimed at reducing blood ammonium levels.
Administration of the non-absorbable disaccharides, have become standard treatment of hepatic encephalopathy.There are no adequate clinical trials comparing the efficacy of L-Ornithine-L-Aspartate (LOLA) infusion against lactose enemas in the treatment of acute hepatic encephalopathy.
Read the detailed description
The main impact of hepatic encephalopathy in patients with cirrhosis is not related to costs, but its association with decreased survival and quality of life and should therefore clearly established the effectiveness of therapeutic interventions used in this disorder.
At the end of the nineteenth century to the ammonium was identified as the main agent responsible for the development of the syndrome of hepatic encephalopathy. Since then, reduced nitrogen compounds from the intestine are considered the main therapeutic measure. On this conceptual base, nonabsorbable disaccharides are the first line therapy in hepatic encephalopathy.
Current knowledge indicates that other organs such as muscle, brain and kidney are involved in the generation of ammonium, which has set the pace for the development of new treatments, able to act systemically in metabolism and elimination of ammonia . L-ornithine L-aspartate (LOLA) lowers ammonium concentrations in animal and humans models with hyperammonemia. There are no adequate clinical trials comparing the efficacy of LOLA infusion against lactose enemas in the treatment of acute hepatic encephalopathy.
- Conditions
- Hepatic Encephalopathy
- Being tested
- L-ornithine-L-aspartate, Lactose
- Keywords
- Encephalopathy, Cirrhosis
- Medical subject headings
- Hepatic Encephalopathy, Brain Diseases, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-ornithine-L-aspartateDrug
Also called LOLA
- Intravenous infusion of 20 g L-ornithine-L-aspartate (4 ampules of 10 mL each) in 250 mL sodium chloride solution administered daily in 4 hours for 3 consecutive days, plus the placebo b) Water enemas, 1000 mL of water and given as retention enema every 12 hours for 3 consecutive days.
LactoseDrug
- 20% Lactose enemas, 200 g Lactose diluted with 700 mL of water and given as retention enema every 12 hours for 3 consecutive days, plus intravenous placebo b)250 mL sodium chloride solution, infusion for 4 hours for 3 consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous infusion of L- Ornithine L- Aspartate | Experimental | a) 20 g L-ornithine-L-aspartate Receives: Drug: L-ornithine-L-aspartate |
| Lactose enemas | Active comparator | b) 20% Lactose enemas Receives: Drug: Lactose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement of at least one grade in mental state based on the West Haven Criteria
Improvement was assessed at 0, 24, 48 and 72 hours. The mental state was scored from trivial lack of awareness to deep coma from grade 1 to grade 4.
Measured: 72 hours
Secondary outcomes (7)
Improvement of at least one grade in mental state assessed by the Glasgow Coma Scale
Improvement was assessed at 0, 24, 48 and 72 hours. The Glasgow Coma Scale assesses three aspects of responsiveness: eye-opening, motor, and verbal responses. The eye-opening was quantified from 1 to 4 points, the motor response from 1 to 6 points and the verbal response from 1 to 5 points.
Measured: 72 hours
Improvement of at least one grade in mental state assessed by the Clinical Hepatic Encephalopathy Staging Scale (CHESS)
Improvement was assessed at 0, 24, 48 and 72 hours. The CHESS scale has 9 dichotomous questions that assess mental state, intellectual function, behavior, verbal and motor response and orientation. It was quantified from 0 to 9 points.
Measured: 72 hours
Improvement of asterixis grade
Improvement was assessed at 0, 24, 48 and 72 hours. Asterixis was graded as follows: Grade 0 = without flapping motion, Grade 1 ≤ 5 flaps per minute, Grade 2 = 6 to 10 flaps per minute, Grade 3 = 11 to 20 flaps per minute and Grade 4, continuous flap or patient in coma unable to maintain wrist dorsiflexion. Asterixis grade was evaluated at 0. 24, 48 and 72 hours.
Measured: 72 hours
Improvement in electroencephalographic tracing grade
Improvement was assessed at 0 and 72 hours. EEG tracing was graduated from 0 to 4: Grade 0 = normal alpha rhythm, Grade 1 =7 to 8 cycles per second, Grade 2= 5 to 6 cycles per second, Grade 3 = 3 to 4.5 cycles per second and Grade 4 < than 3 cycles per second or delta rhythm. EEG was assessed at 0 and 72 hours.
Measured: 72 hours
Improvement in serum ammonia
Ammonia determination was performed at 0, 24, 48 and 72 hours.
Measured: 72 hours
Improvement in Number connection tests
The mental state of the patients included in the study did not allow them to perform the number connection test, therefore, they were all assigned to the worst score (Grade 4)
Measured: 72 hours
Improvement in Portosystemic Encephalopathy Index.
Improvement was assessed at 0 and 72 hours. The PSE Index was calculated by multiplying the grade of mental state by a factor of 3; and the grades of asterixis, number connection tests, serum ammonia and EEG were multiplied times a factor of 1. The results were divided by the maximal possible PSE sum.
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2010 (estimated)
- Study startNov 2009
- Primary completionJun 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centro Regional para el Estudio de las Enfermedades Digestivas
- Sponsor type
- University, hospital or other
- Collaborators
- MERZ PHARMA
- Responsible party
- Principal investigator, Dr. Claudia Isabel Blanco Vela, Centro Regional para el Estudio de las Enfermedades Digestivas
- Investigators
- Francisco J Bosques, MD, PhD, Study director, Centro Regional para el Estudio de las Enfermedades DigestivasClaudia Isabel Blanco Vela, MD, Principal investigator, Hospital Juárez de México
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01041755
- Sponsor's protocol ID
- MI09-002
- Status last verified
- May 2021
- First submitted
- 31 Dec 2009
- Last updated
- 10 May 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Infusion of L-Ornithine L-aspart is as Effective as Nonabsorbable Disaccharides in the Management of Acute Hepatic Encephalopathy.
- ClinicalTrials.gov ID
- NCT01041755
- Acronym / sponsor ID
- MI09-002
- Conditions
- Hepatic Encephalopathy
- Keywords
- Encephalopathy, Cirrhosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Centro Regional para el Estudio de las Enfermedades DigestivasUniversity, hospital or other
- Collaborators
- MERZ PHARMA
- Study start
- Nov 2009 (actual)
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 1 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hepatic encephalopathy is caused by the effects on the brain of substances that under normal circumstances are efficiently metabolized in the liver. The hyperammonemia is the main factor responsible for the development of hepatic encephalopathy. In patients with cirrhosis, the reduction in hepatocellular function and generation of portosystemic shunts contribute to increase serum ammonium. The current therapeutic approaches, are aimed at reducing blood ammonium levels.
Administration of the non-absorbable disaccharides, have become standard treatment of hepatic encephalopathy.There are no adequate clinical trials comparing the efficacy of L-Ornithine-L-Aspartate (LOLA) infusion against lactose enemas in the treatment of acute hepatic encephalopathy.
Detailed description
The main impact of hepatic encephalopathy in patients with cirrhosis is not related to costs, but its association with decreased survival and quality of life and should therefore clearly established the effectiveness of therapeutic interventions used in this disorder.
At the end of the nineteenth century to the ammonium was identified as the main agent responsible for the development of the syndrome of hepatic encephalopathy. Since then, reduced nitrogen compounds from the intestine are considered the main therapeutic measure. On this conceptual base, nonabsorbable disaccharides are the first line therapy in hepatic encephalopathy.
Current knowledge indicates that other organs such as muscle, brain and kidney are involved in the generation of ammonium, which has set the pace for the development of new treatments, able to act systemically in metabolism and elimination of ammonia . L-ornithine L-aspartate (LOLA) lowers ammonium concentrations in animal and humans models with hyperammonemia. There are no adequate clinical trials comparing the efficacy of LOLA infusion against lactose enemas in the treatment of acute hepatic encephalopathy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous infusion of L- Ornithine L- Aspartate | Experimental | Drug: L-ornithine-L-aspartatea) 20 g L-ornithine-L-aspartate |
| Lactose enemas | Active comparator | Drug: Lactoseb) 20% Lactose enemas |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with cirrhosis of any etiology, diagnosed by ultrasound,clinical and / or histologic criteria
- Patients over 18 years and under 75
- Patients with hepatic encephalopathy grade 3-4 according to the criteria of West Haven
- Patients with hyperammonemia >10 µmol/l
Key exclusion criteria (4 listed)
- Evidence of neurological or psychiatric illness
- Use of drugs affecting the central nervous system
- Withdrawal Syndrome
- Anorectal disease that interferes with the administration of enemas
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-ornithine-L-aspartateAlso: LOLAa) Intravenous infusion of 20 g L-ornithine-L-aspartate (4 ampules of 10 mL each) in 250 mL sodium chloride solution administered daily in 4 hours for 3 consecutive days, plus the placebo b) Water enemas, 1000 mL of water and given as retention enema every 12 hours for 3 consecutive days. | Drug | Intravenous infusion of L- Ornithine L- Aspartate |
| Lactosea) 20% Lactose enemas, 200 g Lactose diluted with 700 mL of water and given as retention enema every 12 hours for 3 consecutive days, plus intravenous placebo b)250 mL sodium chloride solution, infusion for 4 hours for 3 consecutive days. | Drug | Lactose enemas |
Primary outcome
Improvement of at least one grade in mental state based on the West Haven Criteria
Time frame: 72 hours
Improvement was assessed at 0, 24, 48 and 72 hours. The mental state was scored from trivial lack of awareness to deep coma from grade 1 to grade 4.
7 secondary outcomes
Improvement of at least one grade in mental state assessed by the Glasgow Coma Scale
Time frame: 72 hours
Improvement of at least one grade in mental state assessed by the Clinical Hepatic Encephalopathy Staging Scale (CHESS)
Time frame: 72 hours
Improvement of asterixis grade
Time frame: 72 hours
Improvement in electroencephalographic tracing grade
Time frame: 72 hours
Improvement in serum ammonia
Time frame: 72 hours
Improvement in Number connection tests
Time frame: 72 hours
Improvement in Portosystemic Encephalopathy Index.
Time frame: 72 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2021.
Related trials for Hepatic Encephalopathy
Not yet recruiting
Effect of Mini-Program Monitoring on Hepatic Encephalopathy in Post-TIPS Patients
Hepatic Encephalopathy, Liver Cirrhosis
Not yet recruitingPhase 4
Daridorexant for Sleep Disturbance in Adults With Liver Cirrhosis
Liver Cirrhosis, Sleep Disturbance
Not yet recruiting
Equivalence of Electronic vs Paper-based PHES in Diagnosing Hepatic Encephalopathy
Liver Cirrhosis, Hepatic Encephalopathy (HE)
Recruiting
4D-Flow MRI Assessment of Portal Hypertension and TIPS Outcomes in Cirrhosis
Cirrhosis, Portal Hypertension
Active, not recruitingPhase 1/2
RTX001 Autologous Engineered Macrophages for Liver Cirrhosis
End-stage Liver Disease (ESLD), Cirrhosis, Liver
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francisco J Bosques, MD, PhD study director
Centro Regional para el Estudio de las Enfermedades Digestivas
Claudia Isabel Blanco Vela, MD principal investigator
Hospital Juárez de México
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing L-ornithine-L-aspartate and Lactose in people with Hepatic Encephalopathy, run by Centro Regional para el Estudio de las Enfermedades Digestivas at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement of at least one grade in mental state based on the West Haven Criteria (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2021.