Efficacy and Safety of Acetyl L-Carnitine in COVID-19 Patients With Mild-to-Moderate Disease

Covid19 Clinical Trial

Official title:

Use of Acetyl L-Carnitine in Patients With Covid-19 Pneumonia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04623619
• Other study ID #: 20201109
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 15, 2020
• Est. completion date: July 31, 2021

Study information

• Verified date: November 2020
• Source: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
• Contact: Antonio Cascio, MD, PhD
• Phone: 3389912198
• Email: antonio.cascio03[@]unipa.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: July 31, 2021
• Est. primary completion date: April 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Covid19

Intervention

Dietary Supplement:
• Acetyl L-Carnitine
Administering 2 gr of Acetyl L-Carnitine orally in addition to the standard of care therapy for 14 days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo

References & Publications (7)

Blanca AJ, Ruiz-Armenta MV, Zambrano S, Miguel-Carrasco JL, González-Roncero FM, Fortuño A, Revilla E, Mate A, Vázquez 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-?B translocation to the nucleus. Food Chem. 2017 Aug 1;228:356-366. doi: 10.1016/j.foodchem.2017.02.011. Epub 2017 Feb 6. — View 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. — View Citation

Görlinger 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. Review. — View 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. Review. — View 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. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In-hospital mortality	Change of hospital mortality	72 hours
Secondary	C reactive protein (CRP) levels	Reduction of CRP levels > 50% in comparison with CRP levels at the admission, within 72 hours after the administration	72 hours
Secondary	IL-6 levels	Reduction of IL-6 levels > 50% in comparison with IL-6 at the admission, within 72 hours after the administration	72 hours
Secondary	D-dimer levels	Reduction of D-dimer levels > 50% in comparison with D-dimer at the admission, within 72 hours after the administration	72 hours
Secondary	Hospital stay	Length of hospital stay	up to 24 weeks
Secondary	Duration of positive PCR swab	Time length of negativization of PCR molecular swab	5 days