Clinical trial NCT04623619: Efficacy and Safety of Acetyl L-Carnitine in COVID-19 Patients With Mild-to-Moderate Disease
Official title: Use of Acetyl L-Carnitine in Patients With Covid-19 Pneumonia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Covid19
Keywords: acetyl L-Carnitine
Lead sponsor: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
Sponsor class: OTHER
First posted: 2020-11-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, open-label, controlled study
Primary purpose: TREATMENT

Brief summary: Different studies showed that acetyl L-Carnitine (LC) positively affects the development and maturation of T lymphocytes, involved in the immune response to viral agents. It also contributes to the inhibition of ROS production and to the remodulation of the cytokine network typical of the systemic inflammatory syndrome.

Given the potential protective effects of LC, it is suggested as a supportive and therapeutic option in patients with coronavirus infection. Given this background, in the light of the current COVID-19 emergency, it is the intention of the investigators to conduct a prospective, randomized, open-label, controlled study in the cohort of hospitalized patients with covid-19 pneumonia, administering 2 gr of LC orally in addition to the standard of care therapy (SOC).

The investigators hypothesize that the use of LC will be associated with an earlier improvement of clinical and biohumoral parameters after 14 days of LC treatment when compared to the group of patients provided with standard care.

Detailed description: Different studies showed that acetyl L-Carnitine (LC) positively affects the development and maturation of T lymphocytes, involved in the immune response to viral agents. It also contributes to the inhibition of ROS production and to the remodulation of the cytokine network typical of the systemic inflammatory syndrome.

SARS-CoV-2 virus activates the human cell ACE2 receptor, triggering a series of deleterious events. In COVID19, renin-angiotensin is upregulated and the pathway is overexpressed and a progressive cytokine storm is always observed. In all these pathogenic processes, LC could play a modifier function to enhance condition. LC can be beneficial to the antioxidant effects of Angiotensin II by inhibiting NF-kB and down-regulating NOX1and NOX2. For LC, an anti-apoptotic and genome-stabilizer role was estimated by inhibiting pro-apoptotic caspases and activating PARP-1. LC is an immunomodulator that downregulates pro-inflammatory cytokines including TNF-α, IL-6, and IL-1 that could extinguish the cytokine storm. LC can also serve as a protective agent against COVID19 cardiotoxicity due to disruption in the ACE2-mediated signaling pathway, cytokine storm, pulmonary dysfunction, and side effects of medications.

In patients with coronavirus infection, provided LC's possible protective effects, it is suggested as a supportive and therapeutic alternative.

Given this background, in the light of the current COVID-19 emergency, it is the intention of the investigators to conduct a prospective, randomized, open-label, controlled study in the cohort of hospitalized patients with covid-19 pneumonia, administering 2 gr of LC orally in addition to the standard of care therapy (SOC).

The investigators hypothesize that the use of LC will be associated with an earlier improvement of clinical and humoral parameters after 14 days of LC treatment when compared to the group of patients provided with standard care.

Eligibility criteria: Inclusion Criteria:

* Positive swab test of SARS-CoV-2
* Pneumonia related to SARS-CoV-2
* Signature of informed consent

Exclusion Criteria:

* Unsigned informed consent
* Negative swab test of SARS-CoV-2

Primary outcomes:
measure: In-hospital mortality
timeFrame: 72 hours
Secondary outcomes:
measure: C reactive protein (CRP) levels
timeFrame: 72 hours
measure: IL-6 levels
timeFrame: 72 hours
measure: D-dimer levels
timeFrame: 72 hours
measure: Hospital stay
timeFrame: up to 24 weeks
measure: Duration of positive PCR swab
timeFrame: 5 days
Other outcomes:
Locations:
Study officials:
affiliation: University of Palermo, Italy
name: Antonio Cascio, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Blanca AJ, Ruiz-Armenta MV, Zambrano S, Miguel-Carrasco JL, Gonzalez-Roncero FM, Fortuno A, Revilla E, Mate A, Vazquez CM. l-Carnitine ameliorates the oxidative stress response to angiotensin II by modulating NADPH oxidase through a reduction in protein kinase c activity and NF-kappaB translocation to the nucleus. Food Chem. 2017 Aug 1;228:356-366. doi: 10.1016/j.foodchem.2017.02.011. Epub 2017 Feb 6.
citation: Puskarich MA, Kline JA, Krabill V, Claremont H, Jones AE. Preliminary safety and efficacy of L-carnitine infusion for the treatment of vasopressor-dependent septic shock: a randomized control trial. JPEN J Parenter Enteral Nutr. 2014 Aug;38(6):736-43. doi: 10.1177/0148607113495414. Epub 2013 Jul 12.
citation: Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, Chen L, Li M, Liu Y, Wang G, Yuan Z, Feng Z, Zhang Y, Wu Y, Chen Y. Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol. 2020 May 1;11:827. doi: 10.3389/fimmu.2020.00827. eCollection 2020.
citation: Moretti S, Alesse E, Di Marzio L, Zazzeroni F, Ruggeri B, Marcellini S, Famularo G, Steinberg SM, Boschini A, Cifone MG, De Simone C. Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study. Blood. 1998 May 15;91(10):3817-24.
citation: Wang ZY, Liu YY, Liu GH, Lu HB, Mao CY. l-Carnitine and heart disease. Life Sci. 2018 Feb 1;194:88-97. doi: 10.1016/j.lfs.2017.12.015. Epub 2017 Dec 11.
citation: Mohammadi M, Hajhossein Talasaz A, Alidoosti M. Preventive effect of l-carnitine and its derivatives on endothelial dysfunction and platelet aggregation. Clin Nutr ESPEN. 2016 Oct;15:1-10. doi: 10.1016/j.clnesp.2016.06.009. Epub 2016 Jun 27.
citation: Gorlinger K, Dirkmann D, Gandhi A, Simioni P. COVID-19-Associated Coagulopathy and Inflammatory Response: What Do We Know Already and What Are the Knowledge Gaps? Anesth Analg. 2020 Nov;131(5):1324-1333. doi: 10.1213/ANE.0000000000005147.