Hepatic EncephalopathyPhase 3NCT00433368
Efficacy of L-Ornithine-L-Aspartate in Cirrhotics With Hepatic Encephalopathy
A Phase 3 study testing L-Ornithine L-Aspartate in people with Hepatic Encephalopathy, run by Aga Khan University at 1 site in Pakistan.
Trial summary
The purpose of this study is to determine whether L-Ornithine L-Aspartate is effective for the improvement of Overt Hepatic Encephalopathy. Read more about this study
- Who is it for?
- Ages 14 to 65 years
- Conditions the study is for
- Hepatic Encephalopathy
- What is being tested?
- L-Ornithine L-Aspartate
- How many people
- 108 participants
- Where
- 1 sitePakistan
- Study dates
- Oct 2003to Sep 2004
- Phase
- Phase 3
- 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 14 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Cirrhosis, diagnosed on the basis of clinical findings, sonographic, and/or histologic basis,
- Patients >14 years, with HE grades 1 to 4 according to West Haven Criteria,
- Hyperammonemia (fasting venous blood ammonia level >60 µmol/l), and
- Patients with a single reversible precipitating factor of HE such as constipation, hypokalemia, urinary tract infection, respiratory tract infection, spontaneous bacterial peritonitis (SBP), dehydration, or none.
Who cannot join
- hepatocellular carcinoma,
- severe septicemia,
- active gastrointestinal bleeding,
- hepatorenal syndrome,
- acute superimposed liver injury,
- advanced cardiac or pulmonary disease and end stage renal failure,
Show all 9Show fewer
- patients with minimal HE
- patients taking sedatives, antidepressants, or benzodiazepines and
- patients with chronic HE on metronidazole or lactulose prior to admission.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of a Three Days' Infusion of L-Ornithine-L-Aspartate as an Adjuvant Therapy in Cirrhotic Patients With Overt Hepatic Encephalopathy: A Placebo Controlled Study
The purpose of this study is to determine whether L-Ornithine L-Aspartate is effective for the improvement of Overt Hepatic Encephalopathy.
Read the detailed description
There is no effective treatment available for hepatic encephalopathy at the moment; therefore we aimed to check the efficacy and safety of L-ornithine L-aspartate(LOLA). It provides critical substrates for ureagenesis and glutamine synthesis, the two primary mechanisms by which the body rids itself of excess ammonia. Ornithine is a specific activator of ornithine carbamyl transferase and carbamylphosphate synthetase, and, in addition, is a substrate for ureagenesis. These reactions are carried out mainly in the periportal portion of the hepatic lobules. Aspartate and ornithine, after conversion to alfa-ketoglutarate, are substrates for glutamine synthesis, which is performed exclusively by a small population of perivenous hepatocytes, the so-called perivenous scavenger cells. The ammonia lowering effect resulting from the stimulation of these two basic mechanisms of ammonia detoxification has been studied in animals and was confirmed in humans in clinical trials.
- Conditions
- Hepatic Encephalopathy
- Being tested
- L-Ornithine L-Aspartate
- Keywords
- L-ornithine-L-aspartate,, porto-systemic encephalopathy,, hepatic encephalopathy,, liver cirrhosis,, mental state
- Medical subject headings
- Hepatic Encephalopathy, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-Ornithine L-AspartateDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in HE grade.
deterioration in HE grade.
Secondary outcomes (3)
Length of hospital stay
fasting ammonia level and
mortality rate
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2007 (estimated)
- Study startOct 2003
- Study completionSep 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 108 participants
Sponsor and investigators
- Lead sponsor
- Aga Khan University
- Sponsor type
- University, hospital or other
- Investigators
- Wasim Jafri, MD; FRCP, Study chair, Chairman Department of Medicine, Aga Khan University HospitalShahab Abid, MD, Principal investigator, Associate Professor, Department of Medicine, Aga Khan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00433368
- Sponsor's protocol ID
- OA001
- Status last verified
- Feb 2007
- First submitted
- 8 Feb 2007
- Last updated
- 9 Feb 2007
- Results posted
- No
Publications
[1] ] STAEDT U, LEWELING H, GLADISCH R, KORTSIK C, HAGMULLER E, HOLM E. Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. J Hepatol 1993;19(3): 424-430. [2] KIRCHEIS G, NILIUS R, HELD C, BERNDT H, BUCHNER M, GÖRTELMEYER R, et al. Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study. Hepatology 1997;25(6):1351-1360. [3] FEHÉR J, LÁNG I, GÓGL A, VARGA L, TOMPOS G, PRÓNAI L. Effect of ornithine-aspartate infusion on elevated serum ammonia concentration in cirrhotic patients - results of a randomized, placebo-controlled double-blind multicentre trial. Med Sci Monit 1997; 3(5):669-673. [4] KIRCHEIS G, WETTSTEIN M, VOM DAHL S, HÄUSSINGER D. Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy. Met Brain Dis 2002;17(4): 453-462. [5] REES CJ, OPPONG K, AL MARDINI H, HUDSON M, RECORD CO. Effect of L- ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: a double blind, placebo controlled trial. Gut 2000; 47(4): 571-574.
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of a Three Days' Infusion of L-Ornithine-L-Aspartate as an Adjuvant Therapy in Cirrhotic Patients With Overt Hepatic Encephalopathy: A Placebo Controlled Study
- ClinicalTrials.gov ID
- NCT00433368
- Acronym / sponsor ID
- OA001
- Conditions
- Hepatic Encephalopathy
- Keywords
- L-ornithine-L-aspartate,, porto-systemic encephalopathy,, hepatic encephalopathy,, liver cirrhosis,, mental state
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants
- Lead sponsor
- Aga Khan UniversityUniversity, hospital or other
- Study start
- Oct 2003
- Study completion
- Sep 2004
- First posted
- 9 Feb 2007 (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.
The purpose of this study is to determine whether L-Ornithine L-Aspartate is effective for the improvement of Overt Hepatic Encephalopathy.
Detailed description
There is no effective treatment available for hepatic encephalopathy at the moment; therefore we aimed to check the efficacy and safety of L-ornithine L-aspartate(LOLA). It provides critical substrates for ureagenesis and glutamine synthesis, the two primary mechanisms by which the body rids itself of excess ammonia. Ornithine is a specific activator of ornithine carbamyl transferase and carbamylphosphate synthetase, and, in addition, is a substrate for ureagenesis. These reactions are carried out mainly in the periportal portion of the hepatic lobules. Aspartate and ornithine, after conversion to alfa-ketoglutarate, are substrates for glutamine synthesis, which is performed exclusively by a small population of perivenous hepatocytes, the so-called perivenous scavenger cells. The ammonia lowering effect resulting from the stimulation of these two basic mechanisms of ammonia detoxification has been studied in animals and was confirmed in humans in clinical trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 14 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Cirrhosis, diagnosed on the basis of clinical findings, sonographic, and/or histologic basis,
- Patients >14 years, with HE grades 1 to 4 according to West Haven Criteria,
- Hyperammonemia (fasting venous blood ammonia level >60 µmol/l), and
- Patients with a single reversible precipitating factor of HE such as constipation, hypokalemia, urinary tract infection, respiratory tract infection, spontaneous bacterial peritonitis (SBP), dehydration, or none.
Key exclusion criteria (9 listed)
- hepatocellular carcinoma,
- severe septicemia,
- active gastrointestinal bleeding,
- hepatorenal syndrome,
- acute superimposed liver injury,
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-Aspartate | Drug | – |
Primary outcome
Improvement in HE grade.
deterioration in HE grade.
3 secondary outcomes
Length of hospital stay
fasting ammonia level and
mortality rate
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 9 Feb 2007.
- Results publication[1] ] STAEDT U, LEWELING H, GLADISCH R, KORTSIK C, HAGMULLER E, HOLM E. Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. J Hepatol 1993;19(3): 424-430. [2] KIRCHEIS G, NILIUS R, HELD C, BERNDT H, BUCHNER M, GÖRTELMEYER R, et al. Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study. Hepatology 1997;25(6):1351-1360. [3] FEHÉR J, LÁNG I, GÓGL A, VARGA L, TOMPOS G, PRÓNAI L. Effect of ornithine-aspartate infusion on elevated serum ammonia concentration in cirrhotic patients - results of a randomized, placebo-controlled double-blind multicentre trial. Med Sci Monit 1997; 3(5):669-673. [4] KIRCHEIS G, WETTSTEIN M, VOM DAHL S, HÄUSSINGER D. Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy. Met Brain Dis 2002;17(4): 453-462. [5] REES CJ, OPPONG K, AL MARDINI H, HUDSON M, RECORD CO. Effect of L- ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: a double blind, placebo controlled trial. Gut 2000; 47(4): 571-574.
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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.
Wasim Jafri, MD; FRCP study chair
Chairman Department of Medicine, Aga Khan University Hospital
Shahab Abid, MD principal investigator
Associate Professor, Department of Medicine, Aga Khan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing L-Ornithine L-Aspartate in people with Hepatic Encephalopathy, run by Aga Khan University at 1 site in Pakistan.
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 9 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 9 Feb 2007. 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 Pakistan. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 in HE grade.. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00433368, which also lists 1 linked publication.
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 9 Feb 2007.