# Supplemental Citicoline Administration for Reduction of Lung Injury Efficacy Trial (SCARLET)

> **NIH NIH U01** · OHIO STATE UNIVERSITY · 2024 · $494,210

## Abstract

The SARS CoV-2 pandemic has resulted in >550,000 deaths in the USA alone. Therapeutic options for critically
ill patients with COVID-19 are limited. Prior studies showed that development of severe hypoxemia and lung
inflammation in influenza A virus-infected mice is associated with inhibition of de novo phospholipid synthesis in
alveolar type II (ATII) cells. Post-infection treatment of influenza A virus-infected mice with the liponucleotide
CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improves gas exchange
and reduces pulmonary inflammation without altering viral replication. In addition, treatment of SARS CoV-2-
infected K18-hACE2-transgenic mice with CDP-choline prevents development of hypoxemia and attenuates lung
inflammation. Finally, treatment of both influenza A-infected and SARS CoV-2-infected human precision cut lung
slices with CDP-choline reduces production of inflammatory mediators. These findings suggest that impaired
ATII cell de novo phospholipid synthesis is a common feature of viral lung injury that contributes significantly to
development of hypoxemia and pulmonary inflammation. It is hypothesized that administration of citicoline (the
pharmaceutical form of CDP-choline, which is approved for human use in Europe) will be safe in critically ill
patients with COVID-19 and that preliminary evidence of clinical benefit to support a larger Phase 2 trial will be
obtained for one or more citicoline doses. These hypotheses will be tested in a milestone-driven, blinded,
placebo-controlled, and randomized Phase 1 dose-ranging and safety study of citicoline in consented adults of
any sex, gender, age, or ethnicity admitted to the ICU with COVID-19. The trial is named “SCARLET”
(Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). SCARLET will show that i.v.
citicoline is safe at one or more of three doses in critically ill COVID-19 patients (20 per dose) and provide
preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy
outcome will be the ratio of blood oxygen saturation to inspired oxygen concentration ( SpO2:FiO2) on Study Day
3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation
index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also
be determined. The study population will consist primarily of COVID-19 patients from underserved minorities in
Columbus and central Appalachia and contingency plans are in place to enroll patients from the University of
Cincinnati should a local decrease in COVID-19 incidence necessitate this. If successful, a Phase 2 trial of
citicoline, incorporating SMART design and with survival as the primary outcome measure, will be conducted to
confirm citicoline efficacy, which could facilitate rapid transition of citicoline to the clinic and potentially transform
the management of crit...

## Key facts

- **NIH application ID:** 10819512
- **Project number:** 5U01AI167784-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** ELLIOTT D CROUSER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $494,210
- **Award type:** 5
- **Project period:** 2022-07-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10819512

## Citation

> US National Institutes of Health, RePORTER application 10819512, Supplemental Citicoline Administration for Reduction of Lung Injury Efficacy Trial (SCARLET) (5U01AI167784-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10819512. Licensed CC0.

---

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