NCT03585257

HEAL STUDY (Hepatic Encephalopathy and Albumin Study)

HEAL STUDY (Hepatic Encephalopathy and Albumin Study): A Double-Blind Randomized Controlled Trial Of Albumin In Hepatic Encephalopathy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (actual)
• Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center · Federal
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Hepatic encephalopathy (HE) is a highly prevalent neuro-cognitive complication of cirrhosis characterized by cognitive dysfunction, and high rate of subsequent mortality and recurrence. HE also places a tremendous burden with a relentless increase in inpatient stay duration with charges topping $7244.7 million in 2009. There were almost 23,000 hospitalizations for HE in 2009 and far more patients with HE who are being managed as an outpatient in the US. In the NACSELD (North American Consortium for the Study of End-Stage Liver Disease) experience supported by Grifols, HE in inpatients is an independent risk factor for mortality and also the leading cause of readmissions in patients with cirrhosis. HE has two major phases, an acute inpatient phase, where patients undergo evaluation for precipitating factors and HE treatment, and the post-discharge phase after HE resolution where the patient has a normal mental status but may be cognitively impaired. Furthermore, it is being increasingly recognized that even after the resolution of an acute HE episode with normal mental status and ability to understand and consent, patients do not regain their pre-HE cognitive function despite maximal therapy with the current standard of care. As many as 70% of patients with HE, despite standard of care, have residual significant cognitive impairments. Studies show that patients with HE, despite being on these medications which are standard of care, continue to have significant cognitive impairment translating into poor health-related quality of life (HRQOL), poor employment status, and very poor socio-economic status. This residual cognitive impairment is proportional to the number of HE episodes and places a heavy medical and socio-economic burden on patients, caregivers and society. In some cases, this approximates a dementia-like situation and makes this situation very difficult to manage. These patients have three options in the current therapeutic situation which can improve brain function. However all of these options have problems in widespread acceptance or eligibility. First, if the patients are hyponatremic, correction of hyponatremia using tolvaptan can help but tolvaptan is now not FDA-approved for cirrhosis. Second a selected group of patients can undergo porto-systemic shunt embolization if their MELD score is \<11 and they have a double shunt, which is the minority of individuals. Lastly a small trial done by our group showed improvement with fecal transplant but this requires several more years of study before this becomes mainstream. Therefore, there is a major need for treating this continued cognitive impairment for which there are currently no widely-available therapeutic agents available but which can improve in selected cases. A medication or strategy that shows improvement in this functioning will be rapidly assimilated into the therapeutic algorithm and will potentially affect several thousand patients and their caregivers who continue to suffer from this issue. There is strong evidence that this persistent cognitive impairment is accompanied by a sustained pro-inflammatory state that is not quenched by our current standard of care15. Ammonia, inflammation, endotoxemia, oxidative stress and endothelial dysfunction play an important role in the pathogenesis of HE. There is also evidence that in patients with advanced cirrhosis, i.e. those who are predisposed to HE, of reduction in albumin concentration and capacity to bind to these metabolites that precipitate HE.

Conditions

• Cirrhosis
• Hepatic Encephalopathy
• Minimal Hepatic Encephalopathy
• Covert Hepatic Encephalopathy

Interventions

Type	Name	Description
BIOLOGICAL	25% IV albumin	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.
OTHER	Placebo	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.

Timeline

• Start date: 2018-06-20
• Primary completion: 2022-02-20
• Completion: 2022-03-30
• First posted: 2018-07-12
• Last updated: 2022-05-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study