Hepatic EncephalopathyPhase 1NCT05700695

Intravenous BCAA for HE in ACLF (BCAA-HE-ACLF)

A Phase 1 study testing Branch Chain Amino Acid and Lactulose in people with Hepatic Encephalopathy and Acute-On-Chronic Liver Failure, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This multi-centric study analyses the effect of intravenous branched-chain amino acids (BCAA) on overt HE in patients with ACLF. The investigators aim to study the efficacy of combining intravenous BCAA with lactulose versus lactulose alone, ammonia measures, endotoxin, metabolomics, and cerebral edema in the medical… Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Hepatic Encephalopathy, Acute-On-Chronic Liver Failure
What is being tested?: Branch Chain Amino Acid and Lactulose
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 114 participants
Where: 1 siteIndia
Study dates: 17 Jan 2023to 5 Jun 2025
Phase: Phase 1
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

Age 18-75 years
Either gender
Patients with ACLF (CANONIC definition) of any etiology with HE ≥grade 2 as per West-Haven Criteria

Who cannot join

Those who do not consent to participate in the study
Patients with structural brain lesions or stroke
Inability to obtain informed consent from patient or relatives
Severe preexisting cardiopulmonary disease
Renal dysfunction (S. Creatinine ≥ 2mg/dL)
Pregnancy/Lactation

Show all 10Show fewer

Post liver transplant patients
HIV infection
Patients who are on psychoactive drugs, like sedatives or antidepressants
Patients who are too sick to carry out the protocol.

Trial locations and contacts

1 site in 1 country.

India1 site

Dr. Madhumita Premkumar
Chandigarh, Chandigarh, 160012

Other trials in India

About this study

Official title: Intravenous Branched-chain Amino Acids for Overt Hepatic Encephalopathy in Patients With Acute on Chronic Liver Failure - A Multi-centric Double-blind Randomized Controlled Trial

Read the detailed description

Treatment of HE in ACLF is based on extrapolation of data available from cirrhotic patients with HE. The mainstay of treatment remains Lactulose. Rifaximin is added on to therapy who have a breakthrough episode of HE on lactulose. BCAA is used as an add-on therapy if patients have minimal/covert encephalopathy, are protein intolerant or have recurrent HE. No studies are available assessing the adjuvant effect of intravenous BCAA on ammonia reduction in HE in patients with ACLF. So, this study has been designed to analyze the effect of intravenous BCAA on hepatic encephalopathy in patients with ACLF. This study will also analyze the systemic and neuronal inflammation, metabolomics, and cerebral edema under the effect of intravenous BCAA in HE patients with ACLF.

Conditions: Hepatic Encephalopathy, Acute-On-Chronic Liver Failure
Being tested: Branch Chain Amino Acid, Lactulose
Keywords: Hepatic Encephalopathy, Acute-On-Chronic Liver Failure, Neurological Dysfunction, Metabolomics, Systemic Inflammations, Branch Chain Amino Acid, bispectral index, Cerebral edema, Lactulose
Medical subject headings: Hepatic Encephalopathy, Acute-On-Chronic Liver Failure, Brain Edema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Branch Chain Amino AcidDrug
Intravenous branched chain amino acids will be given for 3 days to patients in experimental arm
LactuloseDrug
Oral lactulose will be given to patients in both arms

Study groups in NCT05700695
Study group	Role	What they receive
Experiential Arm	Experimental	Drug: iv Branch Chain Amino Acid + Lactulose Intravenous Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose Receives: Drug: Branch Chain Amino Acid; Drug: Lactulose
Comparator Arm	Active comparator	Drug: Lactulose + Placebo of IV BCAA solution Receives: Drug: Lactulose

What is being measured

The primary outcome is the main question the study is designed to answer.

Survival
Survival assessment will be made by recording all deaths
Measured: Day 28

Secondary outcomes (10)

Reduction of arterial ammonia Level
Level of ammonia will be measured by Point of care device
Measured: Day 3
Reduction of arterial ammonia Level
Level of ammonia will be measured by Point of care device
Measured: Day 7
Assessment of cerebral edema
Cerebral edema will be assessed by Magnetic Resonance Imaging+ Magnetic Resonance Spectroscopy
Measured: Discharge form Hospital and 3 month of episode of HE
Prevention/reduction of cerebral edema based on optic nerve sheath diameter (ONSD)
ONSD measurement will be done by Ultrasound
Measured: 72 Hours
Reduction of consciousness recovery time among survivors
Consciousness will be assessed by cognitive battery tests
Measured: Day 28
Survival
Survival assessment will be done with recording all cause mortality
Measured: Day 28
Survival
Survival assessment will be done with recording all cause mortality
Measured: Day 90
Improvement of encephalopathy by one or more grade
Improvement in scoring of hepatic Encephalopathy
Measured: Day 7
Assessment of metabolomics following BCAA + Lactulose and Lactulose alone
Metabolomics will be performed by LC/GC-MS
Measured: Day 7
Dynamic Assessment of systemic inflammation (Cytokines: IL-1b, IL-6, INF-g, TNF-a, IL-15, IL-17, IL-18) at presentation and after Specific management.
Systemic inflammation will be accessed by Cytometric Bead Array
Measured: Day 0

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Jan 20235 Jun 2025

First posted26 Jan 2023
Study start17 Jan 2023
Primary completion5 Jun 2025
Study completion5 Jun 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (11)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 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Prospective interventional cohort study
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 114 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05700695
Sponsor's protocol ID: IEC/04/2022-2385
Status last verified: Jun 2025
First submitted: 6 Dec 2022
Last updated: 8 Jun 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Shawcross DL, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, Taylor NJ, Auzinger G, Bernal W, Wendon JA. Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis. J Hepatol. 2011 Apr;54(4):640-9. doi: 10.1016/j.jhep.2010.07.045. Epub 2010 Dec 1.
PubMed 21163546
Norenberg MD, Martinez-Hernandez A. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 1979 Feb 2;161(2):303-10. doi: 10.1016/0006-8993(79)90071-4.
PubMed 31966
Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology. 2006 Oct;44(4):788-94. doi: 10.1002/hep.21357.
PubMed 17006913
Donovan JP, Schafer DF, Shaw BW Jr, Sorrell MF. Cerebral oedema and increased intracranial pressure in chronic liver disease. Lancet. 1998 Mar 7;351(9104):719-21. doi: 10.1016/S0140-6736(97)07373-X.
PubMed 9504517
Laake JH, Takumi Y, Eidet J, Torgner IA, Roberg B, Kvamme E, Ottersen OP. Postembedding immunogold labelling reveals subcellular localization and pathway-specific enrichment of phosphate activated glutaminase in rat cerebellum. Neuroscience. 1999;88(4):1137-51. doi: 10.1016/s0306-4522(98)00298-x.
PubMed 10336125
Fischer JE, Rosen HM, Ebeid AM, James JH, Keane JM, Soeters PB. The effect of normalization of plasma amino acids on hepatic encephalopathy in man. Surgery. 1976 Jul;80(1):77-91.
PubMed 818729
Rossi-Fanelli F, Riggio O, Cangiano C, Cascino A, De Conciliis D, Merli M, Stortoni M, Giunchi G. Branched-chain amino acids vs lactulose in the treatment of hepatic coma: a controlled study. Dig Dis Sci. 1982 Oct;27(10):929-35. doi: 10.1007/BF01316578.
PubMed 6749458
Cordoba J, Ventura-Cots M, Simon-Talero M, Amoros A, Pavesi M, Vilstrup H, Angeli P, Domenicali M, Gines P, Bernardi M, Arroyo V; CANONIC Study Investigators of EASL-CLIF Consortium. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF). J Hepatol. 2014 Feb;60(2):275-81. doi: 10.1016/j.jhep.2013.10.004. Epub 2013 Oct 12.
PubMed 24128414
Dam G, Aamann L, Vistrup H, Gluud LL. The role of Branched Chain Amino Acids in the treatment of hepatic Encephalopathy. J Clin Exp Hepatol. 2018 Dec;8(4):448-451. doi: 10.1016/j.jceh.2018.06.004. Epub 2018 Jun 27.
PubMed 30568347
Gluud LL, Dam G, Les I, Cordoba J, Marchesini G, Borre M, Aagaard NK, Vilstrup H. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2015 Feb 25;(2):CD001939. doi: 10.1002/14651858.CD001939.pub2.
PubMed 25715177
Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatology. 2009 Dec;50(6):2014-21. doi: 10.1002/hep.23216. No abstract available.
PubMed 19787808

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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

All Hepatic Encephalopathy trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Intravenous Branched-chain Amino Acids for Overt Hepatic Encephalopathy in Patients With Acute on Chronic Liver Failure - A Multi-centric Double-blind Randomized Controlled Trial
ClinicalTrials.gov ID: NCT05700695
Acronym / sponsor ID: IEC/04/2022-2385
Conditions: Hepatic Encephalopathy, Acute-On-Chronic Liver Failure
Keywords: Hepatic Encephalopathy, Acute-On-Chronic Liver Failure, Neurological Dysfunction, Metabolomics, Systemic Inflammations, Branch Chain Amino Acid, bispectral index, Cerebral edema
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 114 participants (actual)
Lead sponsor: Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
Collaborators: Amrita Institute of Medical Sciences & Research Center, Asian Institute of Gastroenterology, India, All India Institute of Medical Sciences, Bhubaneswar, Kalinga Institute of Medical Sciences, Bhubaneswar
Study start: 17 Jan 2023 (actual)
Primary completion: 5 Jun 2025 (actual)
Study completion: 5 Jun 2025 (actual)
First posted: 26 Jan 2023 (actual)
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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Prospective interventional cohort study

Arm	Type	Receives
Experiential Arm	Experimental	Drug: Branch Chain Amino Acid, Drug: LactuloseDrug: iv Branch Chain Amino Acid + Lactulose Intravenous Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose
Comparator Arm	Active comparator	Drug: LactuloseDrug: Lactulose + Placebo of IV BCAA solution

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Age 18-75 years
Either gender
Patients with ACLF (CANONIC definition) of any etiology with HE ≥grade 2 as per West-Haven Criteria

Key exclusion criteria (10 listed)

Those who do not consent to participate in the study
Patients with structural brain lesions or stroke
Inability to obtain informed consent from patient or relatives
Severe preexisting cardiopulmonary disease
Renal dysfunction (S. Creatinine ≥ 2mg/dL)

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
Branch Chain Amino AcidIntravenous branched chain amino acids will be given for 3 days to patients in experimental arm	Drug	Experiential Arm
LactuloseOral lactulose will be given to patients in both arms	Drug	Comparator Arm, Experiential Arm

Primary outcome

Survival
Time frame: Day 28
Survival assessment will be made by recording all deaths

10 secondary outcomes

Reduction of arterial ammonia Level
Time frame: Day 3
Reduction of arterial ammonia Level
Time frame: Day 7
Assessment of cerebral edema
Time frame: Discharge form Hospital and 3 month of episode of HE
Prevention/reduction of cerebral edema based on optic nerve sheath diameter (ONSD)
Time frame: 72 Hours
Reduction of consciousness recovery time among survivors
Time frame: Day 28
Survival
Time frame: Day 28
Survival
Time frame: Day 90
Improvement of encephalopathy by one or more grade
Time frame: Day 7
Assessment of metabolomics following BCAA + Lactulose and Lactulose alone
Time frame: Day 7
Dynamic Assessment of systemic inflammation (Cytokines: IL-1b, IL-6, INF-g, TNF-a, IL-15, IL-17, IL-18) at presentation and after Specific management.
Time frame: Day 0

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 8 Jun 2025.
Background: PubMed 21163546Shawcross DL, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, Taylor NJ, Auzinger G, Bernal W, Wendon JA. Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis. J Hepatol. 2011 Apr;54(4):640-9. doi: 10.1016/j.jhep.2010.07.045. Epub 2010 Dec 1.
Background: PubMed 31966Norenberg MD, Martinez-Hernandez A. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 1979 Feb 2;161(2):303-10. doi: 10.1016/0006-8993(79)90071-4.
Background: PubMed 17006913Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology. 2006 Oct;44(4):788-94. doi: 10.1002/hep.21357.
Background: PubMed 9504517Donovan JP, Schafer DF, Shaw BW Jr, Sorrell MF. Cerebral oedema and increased intracranial pressure in chronic liver disease. Lancet. 1998 Mar 7;351(9104):719-21. doi: 10.1016/S0140-6736(97)07373-X.
Background: PubMed 10336125Laake JH, Takumi Y, Eidet J, Torgner IA, Roberg B, Kvamme E, Ottersen OP. Postembedding immunogold labelling reveals subcellular localization and pathway-specific enrichment of phosphate activated glutaminase in rat cerebellum. Neuroscience. 1999;88(4):1137-51. doi: 10.1016/s0306-4522(98)00298-x.
Background: PubMed 818729Fischer JE, Rosen HM, Ebeid AM, James JH, Keane JM, Soeters PB. The effect of normalization of plasma amino acids on hepatic encephalopathy in man. Surgery. 1976 Jul;80(1):77-91.
Background: PubMed 6749458Rossi-Fanelli F, Riggio O, Cangiano C, Cascino A, De Conciliis D, Merli M, Stortoni M, Giunchi G. Branched-chain amino acids vs lactulose in the treatment of hepatic coma: a controlled study. Dig Dis Sci. 1982 Oct;27(10):929-35. doi: 10.1007/BF01316578.
Background: PubMed 24128414Cordoba J, Ventura-Cots M, Simon-Talero M, Amoros A, Pavesi M, Vilstrup H, Angeli P, Domenicali M, Gines P, Bernardi M, Arroyo V; CANONIC Study Investigators of EASL-CLIF Consortium. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF). J Hepatol. 2014 Feb;60(2):275-81. doi: 10.1016/j.jhep.2013.10.004. Epub 2013 Oct 12.
Background: PubMed 30568347Dam G, Aamann L, Vistrup H, Gluud LL. The role of Branched Chain Amino Acids in the treatment of hepatic Encephalopathy. J Clin Exp Hepatol. 2018 Dec;8(4):448-451. doi: 10.1016/j.jceh.2018.06.004. Epub 2018 Jun 27.
Background: PubMed 25715177Gluud LL, Dam G, Les I, Cordoba J, Marchesini G, Borre M, Aagaard NK, Vilstrup H. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2015 Feb 25;(2):CD001939. doi: 10.1002/14651858.CD001939.pub2.
Background: PubMed 19787808Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatology. 2009 Dec;50(6):2014-21. doi: 10.1002/hep.23216. No abstract available.
Individual participant dataSharing planned: No

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.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 3 inclusion and 10 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 8 Jun 2025. 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 India. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Survival (time frame: Day 28). 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 NCT05700695, which also lists 11 linked publications.

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 8 Jun 2025.