Citicoline for Coronavirus-related Lung Injury

(SCARLET Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Ohio State University

Must not be taking: L-Dopa, Centrophenoxine, Meclofenoxate

Disqualifiers: ECMO, Hypertonia, Pregnancy, others

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if citicoline, given through a vein, is safe and helpful for adults with severe COVID-19 who have trouble breathing. The study aims to see if citicoline can improve oxygen levels and reduce illness severity. Patients will receive either citicoline or another treatment, and their oxygen levels will be monitored regularly.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, specifically those containing L-Dopa, centrophenoxine, or meclofenoxate, as they are listed in the exclusion criteria. For other medications, the protocol does not specify, so it's best to discuss with the study team.

What evidence supports the effectiveness of the drug citicoline for coronavirus-related lung injury?

Research shows that citicoline has beneficial effects in conditions involving low oxygen levels, such as in animal studies where it prolonged survival under extreme hypoxia (low oxygen). It also supports brain cell function and repair, which might indirectly suggest potential benefits for lung injury recovery. ^{1 2 3 4 5}

Is citicoline generally safe for human use?

Citicoline has been shown to be generally safe in humans, with a large study reporting side effects in only 5% of patients, mostly mild digestive issues. In healthy volunteers, transient headaches were the only side effect noted during short-term use. ^{1 3 6 7 8}

How does the drug citicoline differ from other treatments for coronavirus-related lung injury?

Citicoline is unique because it is primarily known for its neuroprotective properties, helping with brain injuries and cognitive issues, but it is being explored for lung injury due to its potential to improve respiratory mechanics and repair lung tissue. Unlike typical lung treatments, citicoline may offer benefits by enhancing brain function and reducing inflammation, which could indirectly support lung recovery. ^{1 2 9 10 11}

Research Team

Eligibility Criteria

Adults with confirmed COVID-19 and acute respiratory failure needing oxygen therapy can join this trial. They must understand the study, not be pregnant or breastfeeding, have no allergies to citicoline, and not take certain medications like L-Dopa. Critically ill patients likely to die soon or on ECMO are excluded.

Inclusion Criteria

I can understand and agree to the study's requirements.

I am 18 years old or older.

Adequate i.v. access available (either peripheral or central venous access)

Exclusion Criteria

I am currently taking medication that contains L-Dopa, centrophenoxine, or meclofenoxate.

Subjects with past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the principal investigator (PI), may pose additional risks from participation in the study or that may impact the quality or interpretation of the data obtained from the study.

I am pregnant or planning to become pregnant.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive i.v. citicoline or saline twice daily for 5 consecutive days

5 days

Daily monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment until hospital discharge or up to 29 days

Up to 29 days

Treatment Details

Interventions

• Supplemental Citicoline Administration (Other)

Trial Overview The SCARLET trial is testing if i.v. citicoline helps adults with severe COVID-19 breathe better compared to a saline placebo. It's double-blinded (neither doctors nor patients know who gets what), randomized (assigned by chance), and checks for safety and improvement in oxygen levels.

Participant Groups

Group I: IV 5 mg/kg/day Citicoline Experimental Treatment 1 Intervention

i.v. bolus of 10 ml normal saline containing 5 mg/kg citicoline, administered twice daily for 5 days.

Group II: IV 10 mg/kg/day Citicoline Experimental Treatment 1 Intervention

i.v. bolus of 10 ml normal saline containing 10 mg/kg citicoline, administered twice daily for 5 days.

Group III: IV 1 mg/kg/day Citicoline Experimental Treatment 1 Intervention

i.v. bolus of 10 ml normal saline containing citicoline 1 mg/kg, administered twice daily for 5 days.

Group IV: IV 10 ml normal saline Placebo Group 1 Intervention

i.v. bolus of 10 ml normal saline (without active ingredient) administered i.v., twice daily for 5 days.

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Dr. John J. Warner

Ohio State University

Chief Executive Officer since 2023

MD, MBA

Dr. Peter Mohler

Ohio State University

Chief Medical Officer since 2023

PhD in Molecular Biology

Findings from Research

A systematic review of 11 clinical studies involving 2771 patients found that citicoline significantly increases the rate of independence in individuals with traumatic brain injury (TBI), with a relative risk of 1.18.

The analysis showed no significant effects on mortality or safety concerns related to citicoline, suggesting it is a safe treatment option for TBI when administered in the acute phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citicoline for the Management of Patients with Traumatic Brain Injury in the Acute Phase: A Systematic Review and Meta-Analysis. Secades, JJ., Trimmel, H., Salazar, B., et al.[2023]

Citicoline shows potential clinical benefits for elderly patients with cognitive deficits and early-stage Alzheimer's disease, acting as a choline donor that supports the production of acetylcholine and neuronal membrane components.

Research indicates that citicoline has cholinergic and neuroprotective effects, which may help improve neuronal membrane integrity and functionality, although its efficacy in stroke patients remains inconclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature. Conant, R., Schauss, AG.[2013]

In a study involving 2817 patients, primarily aged 60 to 80, oral CDP-choline (citicoline) significantly improved symptoms of dizziness (48.4% improvement), headaches (46.5%), and insomnia (38.6%) over treatment periods of 15 days to 2 months.

The safety profile of CDP-choline was excellent, with only 5.01% of patients experiencing side effects, mainly mild digestive issues in 3.6% of cases, indicating it is a well-tolerated treatment option for neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral CDP-choline. Drug surveillance study in 2817 cases. Lozano Fernández, R.[2013]

In a study involving 72 Wistar rats exposed to chronic hypoxia for 6 months, those treated with CDP-choline showed significantly less severe pathological symptoms and a longer survival time compared to untreated rats.

CDP-choline demonstrated a life-prolonging effect under extreme hypoxic conditions, suggesting its potential as a protective intervention in low-oxygen environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increase of survival time in experimental hypoxia by cytidine diphosphate choline. Hamdorf, G., Cervós-Navarro, J., Müller, R.[2016]

The study assessed the acute toxicity of a single dose of CDP-choline (citicoline) in mice and rats, determining the lethal dose (LD50) values to understand its safety profile.

Different administration routes were evaluated, providing insights into how the method of delivery may affect the toxicity of CDP-choline, which is important for its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDP-choline: acute toxicity study. Grau, T., Romero, A., Sacristán, A., et al.[2013]

In a study involving 12 healthy adult volunteers, CDP-choline (citicoline) was administered in two different doses (600 mg and 1 g per day) over 5 days, showing that it is generally well-tolerated with minimal side effects.

The only reported adverse effects were transient headaches in a few participants, indicating that CDP-choline has a favorable safety profile compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDP-choline: repeated oral dose tolerance studies in adult healthy volunteers. Dinsdale, JR., Griffiths, GK., Castelló, J., et al.[2013]

Citicoline may help manage cognitive decline and neurological complications related to COVID-19 due to its properties that support brain cell structure and function, as well as its anti-inflammatory and neuroprotective effects.

The review suggests that citicoline could serve as an adjunctive therapy for post-COVID-19 cognitive issues, highlighting the need for future clinical trials to explore its efficacy in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citicoline and COVID-19-Related Cognitive and Other Neurologic Complications. Turana, Y., Nathaniel, M., Shen, R., et al.[2022]

Citicoline is currently approved in Europe and Japan for treating stroke and other neurological disorders, and is undergoing phase II/III trials in the U.S., indicating its potential as a therapeutic option.

The mechanism of action for citicoline involves providing essential substrates for neuronal membrane repair and enhancing acetylcholine synthesis, which may help in recovery from stroke and reduce toxicity from ischemic damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citicoline (CDP-choline): mechanisms of action and effects in ischemic brain injury. D'Orlando, KJ., Sandage, BW.[2019]

Citicolin shows potential benefits in pulmonology, including preventing acute respiratory distress syndrome in neonates and improving chronic respiratory insufficiency.

It may also enhance respiratory mechanics in conditions with hyperelastic lungs and aid in recovering gas exchange in the alveolo-capillary barrier, suggesting a multifaceted role in respiratory therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The place of citicolin in pulmonological therapy (author's transl)]. Cornia, G., Gramiccioni, E.[2013]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Citicoline for the Management of Patients with Traumatic Brain Injury in the Acute Phase: A Systematic Review and Meta-Analysis. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature. [2013]

3. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral CDP-choline. Drug surveillance study in 2817 cases. [2013]

4. Germany pubmed.ncbi.nlm.nih.gov

Increase of survival time in experimental hypoxia by cytidine diphosphate choline. [2016]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Cardiovascular effects of intracerebroventricularly injected CDP-choline in normotensive and hypotensive animals: the involvement of cholinergic system. [2014]

7. Germany pubmed.ncbi.nlm.nih.gov

CDP-choline: acute toxicity study. [2013]

8. Germany pubmed.ncbi.nlm.nih.gov

CDP-choline: repeated oral dose tolerance studies in adult healthy volunteers. [2013]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Citicoline and COVID-19-Related Cognitive and Other Neurologic Complications. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Citicoline (CDP-choline): mechanisms of action and effects in ischemic brain injury. [2019]

11. Germany pubmed.ncbi.nlm.nih.gov

[The place of citicolin in pulmonological therapy (author's transl)]. [2013]