# Integrated, Individualized, and Intelligent Prescribing (I3P) Clinical Trial Network

> **NIH NIH U01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $693,240

## Abstract

The promise of genomic medicine to transform healthcare and improve health will not be fully realized until
discoveries become relevant to and available for use by diverse populations and their clinicians. As part of the
IGNITE II network, we are proposing two prospective randomized pragmatic genotype-guided clinical trials
(GUARDD-US and ADOPT-PGx) to determine the impact of implementing genetic testing on hypertension,
depression, and pain therapies.
 GUARDD-US: Chronic kidney disease (CKD) is associated with hypertension. People with African ancestry
(AAs) have the highest risk of CKD and kidney failure, the highest prevalence of hypertension, and the lowest
rate of blood pressure (BP) control. While this disparity is in part due to social determinants, ancestry has
biological underpinnings and APOL1 high-risk genetic variants, nearly exclusive found in AAs, increase kidney
failure risk 10-fold. We propose a genotype-guided trial to determine the effect of early vs. delayed knowledge
of a positive APOL1 genotyping result on 3-month systolic blood pressure (SBP). The trial aims to recruit 5435
African Americans with hypertension, with or without CKD, randomized to immediate versus delayed return of
APOL1 genetic testing. In those who are APOL1 negative, we will also conduct a pilot study to test the impact
of pharmacogenetic (PGx) testing on SBP. Secondary outcomes include 6-month SBP, in CKD patients, on
medications ordered, renal diagnosis and testing patient psycho-behavioral outcomes, cost effectiveness, and
the effect of PGX guided hypertension management on SBP.
 ADOPT-PGx: Pain and depression are conditions that impact substantial proportions of the US population.
The treatment of acute and chronic pain is challenged by the difficulty of finding effective therapies while
minimizing the risk of adverse effects or opioid addiction. For depression, there are few clinically relevant
predictors of successful treatment, which results in inadequate therapy for many patients. Both opioid and
antidepressant prescriptions can be guided by PGx data based on existing guidelines from the Clinical
Pharmacogenetics Implementation Consortium (CPIC). We propose a prospective randomized pragmatic
genotype-guided clinical trial that tests the effect of genotype-guided therapy in three scenarios of patients:
acute post-surgical pain, chronic pain, and depression. For each scenario, participants will be randomized to
genotype-guided drug therapy versus usual approaches to drug therapy selection. Changes in patient reported
outcomes representing pain and depression control using standard PROMIS scales define the primary
endpoints. Secondary analyses include safety endpoints, changes in overall well-being, and economic impact
represented by differences in healthcare utilization.
 We expect the successful results from these clinical trials will provide critical evidence needed to drive the
implementation of genomic medicine across broad demographics of patient ...

## Key facts

- **NIH application ID:** 11069604
- **Project number:** 3U01HG010232-05S2
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Kerri Cavanaugh
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $693,240
- **Award type:** 3
- **Project period:** 2024-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11069604

## Citation

> US National Institutes of Health, RePORTER application 11069604, Integrated, Individualized, and Intelligent Prescribing (I3P) Clinical Trial Network (3U01HG010232-05S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11069604. Licensed CC0.

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