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

Primary Purpose

Covid19

Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Acetyl L-Carnitine
Sponsored by
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid19 focused on measuring acetyl L-Carnitine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    No Intervention

    Arm Label

    Acetyl L-Carnitine

    Standard of care

    Arm Description

    Acetyl L-Carnitine

    Standard of care

    Outcomes

    Primary Outcome Measures

    In-hospital mortality
    Change of hospital mortality

    Secondary Outcome Measures

    C reactive protein (CRP) levels
    Reduction of CRP levels > 50% in comparison with CRP levels at the admission, within 72 hours after the administration
    IL-6 levels
    Reduction of IL-6 levels > 50% in comparison with IL-6 at the admission, within 72 hours after the administration
    D-dimer levels
    Reduction of D-dimer levels > 50% in comparison with D-dimer at the admission, within 72 hours after the administration
    Hospital stay
    Length of hospital stay
    Duration of positive PCR swab
    Time length of negativization of PCR molecular swab

    Full Information

    First Posted
    November 9, 2020
    Last Updated
    November 15, 2020
    Sponsor
    Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04623619
    Brief Title
    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

    2. Study Status

    Record Verification Date
    November 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    December 15, 2020 (Anticipated)
    Primary Completion Date
    April 29, 2021 (Anticipated)
    Study Completion Date
    July 31, 2021 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Covid19
    Keywords
    acetyl L-Carnitine

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    Prospective, randomized, open-label, controlled study
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Acetyl L-Carnitine
    Arm Type
    Experimental
    Arm Description
    Acetyl L-Carnitine
    Arm Title
    Standard of care
    Arm Type
    No Intervention
    Arm Description
    Standard of care
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Acetyl L-Carnitine
    Intervention Description
    Administering 2 gr of Acetyl L-Carnitine orally in addition to the standard of care therapy for 14 days
    Primary Outcome Measure Information:
    Title
    In-hospital mortality
    Description
    Change of hospital mortality
    Time Frame
    72 hours
    Secondary Outcome Measure Information:
    Title
    C reactive protein (CRP) levels
    Description
    Reduction of CRP levels > 50% in comparison with CRP levels at the admission, within 72 hours after the administration
    Time Frame
    72 hours
    Title
    IL-6 levels
    Description
    Reduction of IL-6 levels > 50% in comparison with IL-6 at the admission, within 72 hours after the administration
    Time Frame
    72 hours
    Title
    D-dimer levels
    Description
    Reduction of D-dimer levels > 50% in comparison with D-dimer at the admission, within 72 hours after the administration
    Time Frame
    72 hours
    Title
    Hospital stay
    Description
    Length of hospital stay
    Time Frame
    up to 24 weeks
    Title
    Duration of positive PCR swab
    Description
    Time length of negativization of PCR molecular swab
    Time Frame
    5 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Antonio Cascio, MD, PhD
    Phone
    3389912198
    Email
    antonio.cascio03@unipa.it
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Antonio Cascio, MD, PhD
    Organizational Affiliation
    University of Palermo, Italy
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    28317735
    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.
    Results Reference
    background
    PubMed Identifier
    23851424
    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.
    Results Reference
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    PubMed Identifier
    32425950
    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.
    Results Reference
    background
    PubMed Identifier
    9573019
    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.
    Results Reference
    background
    PubMed Identifier
    29241711
    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.
    Results Reference
    background
    PubMed Identifier
    28531771
    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.
    Results Reference
    background
    PubMed Identifier
    33079850
    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.
    Results Reference
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    Efficacy and Safety of Acetyl L-Carnitine in COVID-19 Patients With Mild-to-Moderate Disease

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