# Brain-based and clinical phenotyping of pain pharmacotherapy in knee OA

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $677,252

## Abstract

ABSTRACT
This proposal is in response to the funding opportunity Research Project Grant (Parent R01 Clinical Trial
Required), FOA number PAR-20-183. This proposal aims to identify specific biomarkers in individual people
with osteoarthritis (OA) pain that will allow definition of responder phenotypes distinct for different therapeutic
interventions. A mechanistic, prospective randomized trial will be undertaken, treating people having moderate
to severe OA pain with either naproxen (a non-steroidal anti-inflammatory agent (NSAID)), duloxetine (a selective
serotonin-norepinephrine reuptake inhibitor) or placebo in a 1:1:1 ratio. Randomization will be stratified by sex
and prior opioid use. Naproxen, duloxetine and placebo are known to have different mechanisms of action and
work at different sites in the pain pathway. Hence, it would be expected that these distinctions would be reflected
in differences in individuals who would respond to each of these interventions. To this end, during the study we
will collect a wide variety of biomarkers including demographics (sex, age), clinical outcome measures,
questionnaires of patient-reported outcomes, neurosensory status (quantitative sensory testing indices), serum-
based biomarkers, and joint and brain imaging. The treatment for each participant and collection of biomarkers
will occur during an initial 6-week period and then be repeated after a 4-week washout to account for the known
within-patient variability. The results obtained will permit the identification of responders (defined by 30% or
greater improvement in pain from baseline with other thresholds also evaluated), and the correlation of biomarker
status at baseline to response. We will then build a model to define the responder phenotype for each
intervention, first using only clinical data and secondly using both clinical and MRI-based brain data. The latter
will permit a further understanding of the mechanisms involved in modulation of the pain pathways by each of
the agents. Particular attention will be given to treatment by sex interactions. The characterization of responder
phenotypes to NSAID, duloxetine and placebo will allow for the practice of personalized medicine, providing the
right drug to the right patient, enhancing therapeutic success, and reducing the risks involved with being treated
with ineffective drugs having serious potential side effects. In addition, this approach will allow for more targeted
and more efficient development of potential new therapeutic agents to treat OA pain.

## Key facts

- **NIH application ID:** 10906980
- **Project number:** 5R01AR081854-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Apkar Vania Apkarian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $677,252
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906980

## Citation

> US National Institutes of Health, RePORTER application 10906980, Brain-based and clinical phenotyping of pain pharmacotherapy in knee OA (5R01AR081854-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10906980. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*