# Implementing genomic medicine through pragmatic trials in diverse and underserved populations across Indiana.

> **NIH NIH U01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $1,479,266

## Abstract

The goals of this project are 1) to recruit minority and underserved patients to the IGNITE II pragmatic clinical
trials (PCT) network; and 2) to test the effects of genotype-guided opioid therapy on pain control and opioid-
related adverse events. Indiana University and the current investigators have previously developed research
infrastructure and protocols for efficiently recruiting study participants from diverse clinical settings across
Indiana. State-wide geocoded electronic health care records and community-related data allow us to identify
and recruit minority study participants and those who live in federally-designated underserved areas. In
coordination with our healthcare institutional partners, our multi-disciplinary team is ideally positioned to apply
lessons learned from IGNITE I to implement a wide range of genomic medicine protocols, contribute to
network-wide analyses, collaborate with other clinical groups, and help influence genomic clinical practice and
policy. Recognizing that abuse of opioid prescriptions has become a national crisis, we propose a PCT of
pharmacogenetic-guided opioid selection and dosing with a goal of optimizing pain control and increasing the
safety of using opioids in clinical practice. Indiana is 9th in the nation in terms of opioid prescriptions per capita
and 17th in overdose deaths. Rural and medically underserved areas found in Indiana are amongst the most
affected. Despite the associated risks, however, opioids are still invaluable to managing many cases of severe
pain. The most commonly prescribed opioids (oxycodone, hydrocodone, codeine, or tramadol) are converted
to pharmacologically active metabolites by the liver enzyme, CYP2D6. However, nearly 10% of patients have
alleles encoding either extremely low or extremely high CYP2D6 activity, warranting altered opioid dosing or
selection. Despite strong evidence and clinical guidelines for using CYP2D6 genetic testing to guide opioid
therapy, it is implemented in very few clinics. Leveraging our expertise in opioid pharmacogenetics, as well as
the ability to identify opioid prescriptions across Indiana and perform clinical CYP2D6 genotyping, we propose
the OPTIMIZE study (Opioid Pharmacogenetics-guided Therapy Implementation to MaximIZe Effectiveness), a
pragmatic, prospective, randomized, clinical trial designed to test the hypothesis that implementing CYP2D6
genotyping improves opioid effectiveness and reduces associated toxicities. Using a cluster randomization
study design (by clinic), study participants (n=1333) will be enrolled into one of two study arms, CYP2D6-
guided opioid selection and dosing (intervention) or standard of care (control). We will recruit individuals who
are either (1) scheduled for surgeries typically requiring post-operative opioids, or (2) prescribed a CYP2D6-
metabolized opioid with evidence of uncontrolled chronic pain based on escalating opioid dose. Primary
outcomes will be self-reported pain control and opioid-relate...

## Key facts

- **NIH application ID:** 10442371
- **Project number:** 5U01HG010245-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Paul Dexter
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,479,266
- **Award type:** 5
- **Project period:** 2018-09-19 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10442371

## Citation

> US National Institutes of Health, RePORTER application 10442371, Implementing genomic medicine through pragmatic trials in diverse and underserved populations across Indiana. (5U01HG010245-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10442371. Licensed CC0.

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