# Novel Therapies for Alcoholic Hepatitis with Sepsis and for Relapse Prevention

> **NIH NIH U01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $63,314

## Abstract

Alcoholic Hepatitis (AH) is a major cause of liver-related morbidity and mortality. There are currently no approved
therapies for severe AH. Two key barriers to drug development for severe AH are: (i) the high frequency of
infection and sepsis which exclude most patients from clinical trials and is yet a major cause of mortality in this
population, and (ii) the high rates of continued alcohol consumption after recovery from the acute illness that
drives long-term mortality and re-hospitalization rates. In response to RFA-AA-18-005, we propose two pilot
studies to begin to tackle these barriers. This will be accomplished by two sequentially performed trials as
follows: Aim 1: To provide “proof of concept” that high-dose ascorbic acid (AscA) administered intravenously
along with antibiotics to subjects with AH who have active infection and sepsis is well-tolerated, safe, reduces
systemic inflammation and is potentially effective for the treatment of AH. This is based on strong preliminary
data indicating that AscA reduces inflammation and progression to multi-organ dysfunction in those with severe
sepsis. Given that AH is associated with severe inflammation, we will test the possibility that AscA may provide
common therapy for both AH and sepsis. We will test a fixed dose established to be safe and potentially effective
in severe sepsis, a comparably sick population to those with AH and sepsis to evaluate its safety, tolerability,
ability to reduce systemic inflammation and to generate preliminary data on its ability to reduce progression to
multi-organ failure, as assessed by a 2-point worsening of the SOFA score. These studies will innovate by
repurposing AscA from its use in severe sepsis to AH with infection, a condition excluded from virtually all AH
clinical trials. Aim 2: To provide “proof of concept” that lorcaserin, a 5HT2CR agonist, is well tolerated, reduces
behavioral laboratory measured impulsivity, and enhances brain connectivity related to response inhibition and
alcohol cue reactivity, and these changes correlate with reduction in alcohol use in survivors of AH. We will
generate data on the safety, tolerability and efficacy of lorcaserin to reduce impulse control and related brain
connectivity in those recovering from AH. We will also generate data on any effects of lorcaserin on alcohol
consumption. This leverages our early data indicating that the 5HT2CR regulates impulsivity and associated
alcohol consumption. Subjects recovering from a bout of AH requiring hospitalization will be enrolled 30-90 days
after initial admission from AH. Thirty AH participants will be randomized to lorcaserin (10 mg twice a day by
mouth) or placebo for four weeks. All participants will undergo two MR imaging sessions, one at baseline and
one after four weeks of treatment with lorcaserin or placebo. Alcohol consumption will be measured at baseline,
during treatment, and followed for one month after withdrawal from treatment to obtain preliminary data o...

## Key facts

- **NIH application ID:** 9987414
- **Project number:** 5U01AA026966-03
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** ARUN J SANYAL
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $63,314
- **Award type:** 5
- **Project period:** 2018-09-22 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987414

## Citation

> US National Institutes of Health, RePORTER application 9987414, Novel Therapies for Alcoholic Hepatitis with Sepsis and for Relapse Prevention (5U01AA026966-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9987414. Licensed CC0.

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