Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06538077
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-04-23
Brief Title:
BCAA vs Rifaximin in Patients With Cirrhosis for Secondary Prophylaxis of HE
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Branch Chain Amino Acids vs Rifaximin in Patients With Cirrhosis for Secondary Prophylaxis of Hepatic Encephalopathy Double-blind Placebo-controlled Multicentric Randomized Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HERB
Brief Summary:
Rationale
Patients who recover from an episode of overt HEOHE are at risk of recurrent episodes of HE and persistent minimal hepatic encephalopathy impacting their daily functioning and mental health
A multicentric pan-India team will evaluate the role of oral branched-chain amino acids BCAA vs Rifaximin as secondary prophylaxis following overt HE as compared with improvement in cognitive function
Novelty
This study is intended to investigate the role of BCAA vs rifaximin as the ideal second-line therapy for HE management recurrence and overall health including cognitive function depression and anxiety
The head-to-head comparison of BCAAlactulose pill-placebo vs rifaximin lactulose powder-placebo ensures minimization of bias and has adequate power to determine rates of recurrence
Objectives
To assess the 1st breakthrough episode of HE during 6months in BCAA vs rifaximin groups as ideal secondary prophylaxis in HE Methodology
Double-blind placebo-controlled double-dummy randomized trial of BCAA supplementation vs rifaximin as the ideal second-line therapy in patients with cirrhosis who have recovered from an episode of OHE Expected Outcome
Ideal second line agent HE prophylaxis rifaximin or BCAA following 1st line lactulose is unclear in an Indian context where dysbiosis and sarcopenia are prevalent and cost of therapy needs to be optimized
Optimal HE management prevents recurrence episodes of HE and improves prognosis neurocognitive function and overall health-related quality of lifeHRQOL
Creation of a management algorithm based deductive models incorporating etiology and severity of liver disease cognitive performance sarcopenia and ammonia and neuropsychiatric impact of using BCAA vs Rifaximin will be created
Patients who recover from an episode of overt HEOHE are at risk of recurrent episodes of HE and persistent minimal hepatic encephalopathy impacting their daily functioning and mental health
A multicentric pan-India team will evaluate the role of oral branched-chain amino acids BCAA vs Rifaximin as secondary prophylaxis following overt HE as compared with improvement in cognitive function
Novelty
This study is intended to investigate the role of BCAA vs rifaximin as the ideal second-line therapy for HE management recurrence and overall health including cognitive function depression and anxiety
The head-to-head comparison of BCAAlactulose pill-placebo vs rifaximin lactulose powder-placebo ensures minimization of bias and has adequate power to determine rates of recurrence
Objectives
To assess the 1st breakthrough episode of HE during 6months in BCAA vs rifaximin groups as ideal secondary prophylaxis in HE Methodology
Double-blind placebo-controlled double-dummy randomized trial of BCAA supplementation vs rifaximin as the ideal second-line therapy in patients with cirrhosis who have recovered from an episode of OHE Expected Outcome
Ideal second line agent HE prophylaxis rifaximin or BCAA following 1st line lactulose is unclear in an Indian context where dysbiosis and sarcopenia are prevalent and cost of therapy needs to be optimized
Optimal HE management prevents recurrence episodes of HE and improves prognosis neurocognitive function and overall health-related quality of lifeHRQOL
Creation of a management algorithm based deductive models incorporating etiology and severity of liver disease cognitive performance sarcopenia and ammonia and neuropsychiatric impact of using BCAA vs Rifaximin will be created
Detailed Description:
Hepatic encephalopathy HE a complex neuropsychiatric syndrome arising from liver dysfunction and the establishment of portosystemic shunts PSS presents a significant clinical challenge marked by a spectrum of cognitive emotional and motor disturbances These conditions necessitate precise diagnostic and therapeutic approaches to mitigate its impact on patient well-being and quality of life
The prevalence of OHE at the time of diagnosis of cirrhosis is 10-14 in general 16-21 in those with decompensated cirrhosis The cumulated numbers indicate that OHE will occur in 30-40 of those with cirrhosis at some time during their clinical course and in the survivors in most cases repeatedly Minimal HE MHE or covert HE CHE occurs in 20-80 of patients with cirrhosis This high incidence rate calls for effective accessible and cost-efficient treatment modalities to improve patient outcomes and quality of life
Indian patients have sarcopenia and reduced muscle strength impairing peripheral ammonia metabolism and also have gut dysbiosis which can predispose to another episode of HE A critical initial step in addressing HE involves the identification of precipitating factors with evidence suggesting that reversible elements contribute to over 80 of HE cases
Current therapeutic interventions primarily target the reduction of blood ammonia levels yet the effectiveness of these treatments varies underscoring the necessity for ongoing research and innovation in HE management
Patients recovering from OHE are at risk of recurrent episodes and may suffer from persistent MHE a condition often undiagnosed due to its subtle cognitive manifestations Such individuals may have cognitive impairment that affect patients daily functioning and mental health necessitating the development of standardized diagnostic psychometric tests protocols tailored to diverse populations
Mainstay for treatment of HE has been lactulose or lactitol How lactulose acts in HE has been a matter of debate and various hypotheses have been postulated Inglefenger et al suggested it to be due to proliferation of Lactobacillus with inhibition of Bacteroides and other organisms 28 Lactulose has pleiotropic effects and reduction of ammonia is only one of the ways in which it acts on HE
Rifaximin is an oral antibiotic having 04 of systemic absorption It acts against coliforms like Escherichia coli and plays a role in the reduction of ammonia levels and prevention of recurrence of HE Several trials have compared Rifaximin as a therapy of HE with placebo neomycin and non-absorbable disaccharides Rifaximin emerged as a promising alternative showing comparable efficacy in managing OHE and preventing its recurrence
This is a double-blind randomized placebo-controlled trial of branched-chain amino acid supplementation vs rifaximin as the ideal second-line therapy in patients with cirrhosis who have recovered from an episode of overt hepatic encephalopathy with either drug given over 24 weeks with endpoints being prevention of recurrence of another episode of HE efficacy safety and improvement in neurocognitive function
The prevalence of OHE at the time of diagnosis of cirrhosis is 10-14 in general 16-21 in those with decompensated cirrhosis The cumulated numbers indicate that OHE will occur in 30-40 of those with cirrhosis at some time during their clinical course and in the survivors in most cases repeatedly Minimal HE MHE or covert HE CHE occurs in 20-80 of patients with cirrhosis This high incidence rate calls for effective accessible and cost-efficient treatment modalities to improve patient outcomes and quality of life
Indian patients have sarcopenia and reduced muscle strength impairing peripheral ammonia metabolism and also have gut dysbiosis which can predispose to another episode of HE A critical initial step in addressing HE involves the identification of precipitating factors with evidence suggesting that reversible elements contribute to over 80 of HE cases
Current therapeutic interventions primarily target the reduction of blood ammonia levels yet the effectiveness of these treatments varies underscoring the necessity for ongoing research and innovation in HE management
Patients recovering from OHE are at risk of recurrent episodes and may suffer from persistent MHE a condition often undiagnosed due to its subtle cognitive manifestations Such individuals may have cognitive impairment that affect patients daily functioning and mental health necessitating the development of standardized diagnostic psychometric tests protocols tailored to diverse populations
Mainstay for treatment of HE has been lactulose or lactitol How lactulose acts in HE has been a matter of debate and various hypotheses have been postulated Inglefenger et al suggested it to be due to proliferation of Lactobacillus with inhibition of Bacteroides and other organisms 28 Lactulose has pleiotropic effects and reduction of ammonia is only one of the ways in which it acts on HE
Rifaximin is an oral antibiotic having 04 of systemic absorption It acts against coliforms like Escherichia coli and plays a role in the reduction of ammonia levels and prevention of recurrence of HE Several trials have compared Rifaximin as a therapy of HE with placebo neomycin and non-absorbable disaccharides Rifaximin emerged as a promising alternative showing comparable efficacy in managing OHE and preventing its recurrence
This is a double-blind randomized placebo-controlled trial of branched-chain amino acid supplementation vs rifaximin as the ideal second-line therapy in patients with cirrhosis who have recovered from an episode of overt hepatic encephalopathy with either drug given over 24 weeks with endpoints being prevention of recurrence of another episode of HE efficacy safety and improvement in neurocognitive function
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None