Hepatic EncephalopathyPhase 1BCAA-ACLFNCT04238416

Intravenous Branched Chain Amino Acids for Hepatic Encephalopathy in ACLF

A Phase 1 study testing Branched 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

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Trial summary

This study analyses the effect of intravenous branched chain amino acids (BCAA) on overt HE in patients with ACLF. The investigators plan to study the efficacy of combining intravenous BCAA with lactulose versus lactulose alone in the medical management of overt HE in patients with ACLF and its impact on overall… 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?: Branched 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: 70 participants
Where: 1 siteIndia
Study dates: 1 Nov 2019to 30 Dec 2021
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 aetiology with HE ≥grade 2 as per West-Haven Criteria or Hepatic encephalopathy scoring algorithm (HESA)

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 11Show 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
As the study was carried out during the peak of the COVID-19, patients who developed COVID-19 after randomization were excluded from the analysis as they were shifted to dedicated COVID-19 ICU's.

Trial locations and contacts

1 site in 1 country.

India1 site

PGIMER
Chandigarh, 160012

Other trials in India

About this study

Official title: Efficacy of Lactulose Plus Intravenous Branched Chain Amino Acids Versus Lactulose Alone in Patients of Acute on Chronic Liver Failure With Overt Hepatic Encephalopathy: A Prospective Randomized Clinical Trial

Read the detailed description

Acute on chronic liver failure (ACLF) is a distinct clinical entity in the spectrum of chronic liver disease associated with high short term mortality. Hepatic encephalopathy (HE) is commonly seen in patients with ACLF and its treatment mainly involves non-absorbable disaccharides (lactulose/lactitol).Treatment of HE in ACLF is based on extrapolation of data available from cirrhotic patients. No studies have compared different treatment options for HE in patients with ACLF.

Conditions: Hepatic Encephalopathy, Acute-On-Chronic Liver Failure
Being tested: Branched chain amino acid, Lactulose
Keywords: branched chain amino acids, hepatic encephalopathy, lactulose, acute on chronic liver failure, bispectral index
Medical subject headings: Hepatic Encephalopathy, Acute-On-Chronic Liver Failure

What participants receive

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

Branched 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 NCT04238416
Study group	Role	What they receive
IV BCAA + Lactulose	Experimental	IV Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose Receives: Drug: Branched chain amino acid; Drug: Lactulose
Lactulose alone	Active comparator	Oral Lactulose alone Receives: Drug: Lactulose

What is being measured

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

Improvement of Survival
All cause Mortality assessment
Measured: At day day 28
Improvement of encephalopathy by ≥ 1 grade
Improvement in hepatic encephalopathy
Measured: 72 hours

Secondary outcomes (4)

Reduction in level of ammonia
Measured: 48 and 72 hours
Reduction of consciousness recovery time among survivors
Measured: 30 days
Prolongation of time to death among non-survivors
Measured: 30 days
Prevention/reduction of cerebral edema based on optic nerve sheath diameter
Measured: 72 hours

Timeline

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

1 Nov 201930 Dec 2021

First posted23 Jan 2020
Study start1 Nov 2019
Primary completion30 Dec 2021
Study completion30 Dec 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (12)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: None (open label)
Enrolment: 70 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04238416
Sponsor's protocol ID: IEC-08/2019-1336
Acronym: BCAA-ACLF
Status last verified: Aug 2022
First submitted: 28 Sep 2019
Last updated: 16 Aug 2022
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
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
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
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, Dolinska M, Hilgier W, Lipkowski AW, Nowacki J. Modulation of glutamine uptake and phosphate-activated glutaminase activity in rat brain mitochondria by amino acids and their synthetic analogues. Neurochem Int. 2000 Apr;36(4-5):341-7. doi: 10.1016/s0197-0186(99)00142-4.
PubMed 10733001
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
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
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
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
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
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
Mehtani R, Premkumar M, Garg S, Kajal K, Kulkarni AV, Duseja AK, Dhiman RK, De A, Verma N, Taneja S, Rathi S, Singh V, Chakma J, Soni SL, Kakkar A, Kapila AT, Ahuja CK, Divyaveer S, Praharaj D. Intravenous BCAA Infusion Does Not Lead to a Sustained Recovery From Overt HE in ACLF - An Open Label Randomized Clinical Trial. J Clin Exp Hepatol. 2023 Nov-Dec;13(6):977-988. doi: 10.1016/j.jceh.2023.05.015. Epub 2023 Jun 1.
PubMed 37975059

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?

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All Hepatic Encephalopathy trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy of Lactulose Plus Intravenous Branched Chain Amino Acids Versus Lactulose Alone in Patients of Acute on Chronic Liver Failure With Overt Hepatic Encephalopathy: A Prospective Randomized Clinical Trial
ClinicalTrials.gov ID: NCT04238416
Acronym / sponsor ID: BCAA-ACLF / IEC-08/2019-1336
Conditions: Hepatic Encephalopathy, Acute-On-Chronic Liver Failure
Keywords: branched chain amino acids, hepatic encephalopathy, lactulose, acute on chronic liver failure, bispectral index
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 70 participants (actual)
Lead sponsor: Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
Study start: 1 Nov 2019 (actual)
Primary completion: 30 Dec 2021 (actual)
Study completion: 30 Dec 2021 (actual)
First posted: 23 Jan 2020 (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: None (open label)
Number of arms: 2
Model description: Prospective interventional cohort study

Arm	Type	Receives
IV BCAA + Lactulose	Experimental	Drug: Branched chain amino acid, Drug: LactuloseIV Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose
Lactulose alone	Active comparator	Drug: LactuloseOral Lactulose alone

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 aetiology with HE ≥grade 2 as per West-Haven Criteria or Hepatic encephalopathy scoring algorithm (HESA)

Key exclusion criteria (11 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
Branched chain amino acidIntravenous branched chain amino acids will be given for 3 days to patients in experimental arm	Drug	IV BCAA + Lactulose
LactuloseOral lactulose will be given to patients in both arms	Drug	IV BCAA + Lactulose, Lactulose alone

Primary outcome

Improvement of Survival
Time frame: At day day 28
All cause Mortality assessment
Improvement of encephalopathy by ≥ 1 grade
Time frame: 72 hours
Improvement in hepatic encephalopathy

4 secondary outcomes

Reduction in level of ammonia
Time frame: 48 and 72 hours
Reduction of consciousness recovery time among survivors
Time frame: 30 days
Prolongation of time to death among non-survivors
Time frame: 30 days
Prevention/reduction of cerebral edema based on optic nerve sheath diameter
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 16 Aug 2022.
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 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 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 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 10733001Albrecht J, Dolinska M, Hilgier W, Lipkowski AW, Nowacki J. Modulation of glutamine uptake and phosphate-activated glutaminase activity in rat brain mitochondria by amino acids and their synthetic analogues. Neurochem Int. 2000 Apr;36(4-5):341-7. doi: 10.1016/s0197-0186(99)00142-4.
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 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.
Results publication: 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.
Results publication: 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.
Results publication: 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.
Results publication: 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.
Derived from this study: PubMed 37975059Mehtani R, Premkumar M, Garg S, Kajal K, Kulkarni AV, Duseja AK, Dhiman RK, De A, Verma N, Taneja S, Rathi S, Singh V, Chakma J, Soni SL, Kakkar A, Kapila AT, Ahuja CK, Divyaveer S, Praharaj D. Intravenous BCAA Infusion Does Not Lead to a Sustained Recovery From Overt HE in ACLF - An Open Label Randomized Clinical Trial. J Clin Exp Hepatol. 2023 Nov-Dec;13(6):977-988. doi: 10.1016/j.jceh.2023.05.015. Epub 2023 Jun 1.
Individual participant dataSharing planned: No

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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.

Madhumita Premkumar, MD, DM principal investigator

Post Graduate Institute of Medical Education and Research, Chandigarh

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 11 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 16 Aug 2022. 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?

Improvement of Survival (time frame: At day day 28). 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 NCT04238416, which also lists 12 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 16 Aug 2022.