# Genomic Predictors of Placebo response in Phase II AUD trials

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $602,932

## Abstract

PROJECT SUMMARY
Placebo response is an important and poorly understood phenomenon of treatment response. A large and
variable placebo response has been evident in decade’s long placebo-controlled double blind clinical trials that
tested various treatments for alcohol use disorders (AUD). Large placebo effects complicate detection of
quantifiable treatment effects for investigational medications, especially for the modestly effective psychiatric
drugs. Placebo response arise from a complex interaction of patient, clinical trial staff, and treatment
environment factors. Because the placebo response is intricate, complex and variable among individuals, it is
challenging to identify these individuals prior to enrollment in a clinical trial. The proposed project seeks to
explore the utility of genomics to identify placebo responders in phase ІІ AUD treatment trials. To date, to the
best of our knowledge, comprehensive genomic studies have not been conducted to assess genetic variation in
relation to outcomes of AUD treatment or placebo response. Genomic analyses require large sample sizes that
are not easy to gather in small to medium scale clinical trials conducted with treatment seeking individuals
with an AUD or other drug use disorder. To address this issue, we will leverage the resources from six
completed and two ongoing NIAAA-funded phase ІІ AUD treatment trials. We will first examine changes in
patterns of drinking among the enrolled treatment-seeking individuals with AUD, during treatment with a
placebo (Aim І). We will then explore how these changes in drinking affect expression of genes, perusing the
entire genome of each individual (Aim ІІ). The genes whose expression levels are found to be changed according
to a person’s drinking behavior or how frequent the person was able to abstain from alcohol, will be fine-
combed to identify DNA sequence (genetic) variations that rendered them susceptible to varying amounts of
alcohol (Aim ІІІ). Next, we will explore whether these genetic variations and the expression patterns of their
genes, can predict placebo response (as measured by abstinence rates) in populations with AUD together with
other psychiatric conditions (cocaine addiction and PTSD; Exploratory Aim І). Finally, we will explore whether
the identified genetic variants and genes are expressed in the same manner in those who have received an
active medication (ondansetron/topiramate/naltrexone) for the treatment of their AUD (Exploratory Aim ІІ),
which may help us understand the placebo component embedded within response to an active medication, at a
molecular level. In summary, our proposed project is conceptually and methodologically innovative in
exploring genetic variations by examining gene expression differences associated with amounts of drinking
during placebo treatment. As the first study to characterize genomics of placebo response in phase ІІ AUD
trials, findings will provide a wealth of information for future translational re...

## Key facts

- **NIH application ID:** 9853704
- **Project number:** 5R01AA026291-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Chamindi Seneviratne
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $602,932
- **Award type:** 5
- **Project period:** 2018-02-10 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853704

## Citation

> US National Institutes of Health, RePORTER application 9853704, Genomic Predictors of Placebo response in Phase II AUD trials (5R01AA026291-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9853704. Licensed CC0.

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