HEAL STUDY (Hepatic Encephalopathy and Albumin Study)

NCT03585257 | Completed Phase 2 FDA Drug

• 1 other identifier: BAJAJ023
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with continued cognitive impairment after episodes of HE have few options beyond lactulose and rifaximin in the US. Therefore using IV albumin in a randomized, double-blind, placebo-controlled trial, which could beneficially impact inflammation, could be an additional approach to improve cognition. This 6 week trial will study changes in cognition, HRQOL and inflammation in patients with covert HE after prior overt HE using multiple IV albumin infusions vs. placebo.

Conditions

Cirrhosis; Hepatic Encephalopathy; Minimal Hepatic Encephalopathy; Covert Hepatic Encephalopathy

Keywords

covert hepatic encephalopathy; inflammation; cognition; quality of life

Outcome Measures

Primary Outcomes (2)

• Improvement in psychometric hepatic encephalopathy score (PHES) from baseline vs end in albumin vs placebo group

  Cognitive improvement on PHES

  5 weeks

• Minimal Hepatic Encephalopathy (MHE) reversal

  change proportion of patients with MHE over time

  5 weeks

Secondary Outcomes (8)

• Change in SIckness Impact Profile (SIP) Questionnaire results from baseline vs end in albumin vs placebo group

  5 weeks

• Change of PHES score to baseline in albumin group after discontinuation

  1 week

• Change of EncephalApp Stroop OffTime+OnTime to baseline in albumin group after discontinuation

  1 week

• Change of CFF results to baseline in albumin group after discontinuation

  1 week

• Change of SIP score to baseline in albumin group after discontinuation

  1 week

Study Arms (2)

IV albumin

EXPERIMENTAL

25% IV albutein (albumin) formulation will be infused 1.0g/kg IV over one hour weekly for 5 weeks

Biological: 25% IV albumin

Placebo

PLACEBO COMPARATOR

Normal saline will be infused 1.0g/kg IV over one hour weekly for 5 weeks

Other: Placebo

Interventions

25% IV albumin BIOLOGICAL

Intravenous 25% albumin infusion 1.0 g/kg body weight (maximum 100gm) once a week for five weeks for a maximum of 5 infusions. These infusions will be administered over sixty minutes per clinical treatment protocols for this population. Patients and investigators will be blinded as to the characteristic of the infusion. Pre-infusion serum albumin will be checked and if \>4.0gm/dl, then normal saline will be given instead as mentioned in the blinding section above. Samples will be collected before and one hour after the infusion for all patients. The total grams of albumin infused over the 4 weeks during and outside the study will be collected and compared between groups.

IV albumin

Placebo OTHER

Normal saline infusion 1.0g/kg body weight once a week for five weeks for a maximum of 5 infusions. These infusions will be administered over sixty minutes per clinical treatment protocols for this population. Patients and investigators will be blinded as to the characteristic of the infusion. Pre-infusion serum albumin will be checked and if \>4.0gm/dl, then normal saline will be given instead as mentioned in the blinding section above. Samples will be collected before and one hour after the infusion for all patients. The total grams of albumin infused over the 4 weeks during and outside the study will be collected and compared between groups.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years
• Cirrhosis defined by any one of the following
• Cirrhosis on liver biopsy or transient wave elastography
• Nodular liver on imaging
• Endoscopic or radiological evidence of varices in a patient with chronic liver disease
• Platelet count \<150,000/mm3 and AST/ALT ratio \>1 in a patient with chronic liver disease
• Patients with frank decompensation (ascites, HE, variceal bleeding, hepato-pulmonary syndrome)
• Prior HE controlled on standard of care therapy defined as lactulose or rifaximin for at least 2 months prior to enrollment.
• Serum albumin \<4 gm/dl
• Cognitive impairment on any of the three testing strategies for HE including Psychometric hepatic encephalopathy score (PHES), Stroop test and Critical Flicker Frequency
• PHES aggregate score \<-4SD based on norms published in Allampati et al located at the website www.encephalapp.com
• Stroop OffTime+OnTime values greater than norms published in Allampati et al located at the website www.encephalapp.com
• Critical Flicker Frequency value \<39 Hz

You may not qualify if:

• Unclear diagnosis of cirrhosis (does not meet the criteria outlined above)
• No prior overt HE episodes
• HE uncontrolled on standard of care defined as a mini-mental status exam\<25
• On regular IV albumin infusions due to scheduled paracentesis within the last 3 months
• Recent alcohol abuse (within 3 months)
• Unable to give consent
• Current or recent invasive bacterial or fungal infections (\<1 month)
• Allergic reactions to IV albumin
• Current or recent congestive heart failure (Systolic ejection fraction \<25%) within the last year
• Pregnancy (positive urine pregnancy test at screening)
• In the opinion of the PI, those who are unlikely to survive 6 weeks or be able to adhere to the trial activities.

Sponsors & Collaborators

• Hunter Holmes Mcguire Veteran Affairs Medical Center: lead
• McGuire Research Institute: collaborator
• Instituto Grifols, S.A.: collaborator

Study Sites (1)

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Related Publications (1)

• Fagan A, Gavis EA, Gallagher ML, Mousel T, Davis B, Puri P, Sterling RK, Luketic VA, Lee H, Matherly SC, Sanyal AJ, Stravitz RT, Patel V, Siddiqui MS, Asgharpour A, Fuchs M, Thacker L, Bajaj JS. A double-blind randomized placebo-controlled trial of albumin in outpatients with hepatic encephalopathy: HEAL study. J Hepatol. 2023 Feb;78(2):312-321. doi: 10.1016/j.jhep.2022.09.009. Epub 2022 Sep 22.

  PMID: 36152764 DERIVED

MeSH Terms

Conditions

Fibrosis; Hepatic Encephalopathy; Inflammation

Interventions

Albumins

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Jasmohan Bajaj, MD

  Hunter Holmes MVAMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Patients will be randomized into receiving IV albumin vs placebo

Study Record Dates

• First Submitted: June 29, 2018
• First Posted: July 12, 2018
• Study Start: June 20, 2018
• Primary Completion: February 20, 2022
• Study Completion: March 30, 2022
• Last Updated: May 31, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)