Clinical Study to Evaluate the Effect of Food Supplement in People Infected With Coronavirus

Pilot Phase II Randomized, Placebo-Controlled Clinical Trial for the Prevention and Progression of SARS-CoV-2 Infection of Subjects and Patients Using a Supplement Treatment With Carnipure Tartrate ( LCLT)

The purpose of the study is to assess safety and efficacy of Carnipure tartrate (L-Carnitine and L-tartaric acid - LCLT) supplementation for SARS-Cov-2 infection

Study Overview

• Status: Completed
• Conditions: COVID-19 Virus Infection
• Intervention / Treatment: Dietary supplement: LCLT : 68% elemental L-carnitine and 32 % Tartric acid; Drug: Placebo

Detailed Description

After being informed about the study and potential risks, all patients given written informed consent will be divided em two cohorts according to inclusion criteria.One group with patients with diagnosed mild SARS-Cov-2 infection and another with healthy contacts of patients with diagnosed mild SARS-Cov-2.

Both groups will be randomized to receive either LCLT supplementation or placebo during 21 days. After this period primary endpoints of efficacy will be assessed.

Clinical follow up evaluations will be monitored (Cohort 1 and 2), and chest tomography will be monitored in cohort 2 as well. Subjects will be followed for safety through 8 weeks (cohort 1) and 6 weeks (cohort 2) after being included into the study.

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 41650-010
      • SENAI CIMATEC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Cohort 1:

   • males and females between 55 years and 85 years of age;
   • history of close contact (cohabit) with a Family member or a person newly diagnosed with SARS-CoV-2 infection;
   • negative RT-PCR COVID-19 test on the screening immediately after contact and prior to start treatment of the study.

2. Cohort 2:

   • males and females between 18 years and 85 years of age;
   • positive RT-PCR COVID-19 test and medical history and physical exam compatible with asymptomatic or mild COVID-19 pneumonia. Evaluation of clinical outcomes: oxygen requirements, hospitalization breathless and others;

   • Female subjects of childbearing potential must :

     • have a negative serum pregnancy test at screening and a negative urine pregnancy test on the day of each study supplementation;
     • no breast-feeding;
     • agree to use one of the following methods of contraception from enrollment in study until 30 days after last supplementation (only if in sexual relationships with men): hormonal (e.g. oral, transdermal, intravaginal, implant, or injection); double barrier (i.e., condom, diaphragm, or cervical cap with spermicide); intrauterine device (IUD) or system (IUS); vasectomized partner (6 months minimum); or abstinence; bilateral tubal ligation (if no conception post-procedure); tubal occlusion; or bilateral salpingectomy. Women are considered non-child-bearing potential if they are post-menopausal (defined as at least 12 months spontaneous amenorrhea and confirmed with FSH > 40 mIU/ml) or have had documented hysterectomy and/or oophorectomy. system (IUS); vasectomized partner (6 months minimum); or abstinence; bilateral tubal ligation (if no conception post-procedure); tubal occlusion; or bilateral salpingectomy;
   • Normal laboratory values of sodium, potassium, ALT, AST, total bilirubin, alcaline phosphatase, creatinine, fasting glucose, total WBC count, hemoglobina and platelet count;
   • No medical history of alcohol or drug abuse

Exclusion Criteria:

• Hormonal replacement therapy;
• Severe COVID-19 pneumonia according to CDC criteria;
• Positive test for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies;
• Participation in another experimental protocol and/or receipt of any investigational products within the past 3 months prior to Screening;
• Immunosuppressive cytotoxic therapies (e.g., chemotherapy drugs or radiation) in the past 6 months prior to Screening;
• Subjects unable to sign the inform consent to participate into the study;
• History of any other acute or uncontrolled chronic illness (including, hypertension, cardiovascular, pulmonary, neurological, hepatic, rheumatic, hematological, metabolic or renal disorders) that is not on medication regimen for at least the past 6 months;
• Medication or supplements that may interfere with the evaluation of the safety and tolerability of the study drug such as ACE Inhibitors, Angiotensin II Receptor Blockers (ARBs) (e.g. vitamin B3 and L-carnitine/acetyl-carnitine).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: covid 19 LCLT supplement; LCLT is made out of 68% elemental L-carnitine and 32 % Tartric acid and therefore the EFSA (European Food Safety Authority) stated that it is safety up to at least 3 g. Each 3 g of LCLT delivers 2 g of elemental L-carnitine L-carnitine and Tartric acid, 3g oral capsules daily use for 21 days	Dietary supplement: LCLT : 68% elemental L-carnitine and 32 % Tartric acid; 3 g orally capsules; Other Names: Carnipure™ Tartrate (LCLT) formulation
Placebo Comparator: covid 19 placebo; The formulation will contain all salt ingredients v/v without LCLT (made out of 68% elemental L-carnitine and 32 % Tartric acid) and is replaced by Maltodextrin in the placebo capsules Placebo capsules daily for 21 days	Drug: Placebo; orally capsules
Active Comparator: Healthy LCLT supplement; LCLT is made out of 68% elemental L-carnitine and 32 % Tartric acid and therefore the EFSA (European Food Safety Authority) stated that it is safety up to at least 3 g. Each 3 g of LCLT delivers 2 g of elemental L-carnitine L-carnitine and Tartric acid, 3g oral capsules daily use for 21 days	Dietary supplement: LCLT : 68% elemental L-carnitine and 32 % Tartric acid; 3 g orally capsules; Other Names: Carnipure™ Tartrate (LCLT) formulation
Placebo Comparator: Healthy Placebo; The formulation will contain all salt ingredients v/v without LCLT (made out of 68% elemental L-carnitine and 32 % Tartric acid) and is replaced by Maltodextrin in the placebo capsules Placebo capsules daily for 21 days	Drug: Placebo; orally capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number new SARS-CoV-2 cases at 21 days assessed by RT-PCR	Number new SARS-CoV-2 cases at 21 days assessed by RT-PCR	21 days
Number of participants with severe COVID pneumonia measured by the presence of ground-glass opacity, consolidations, parenchymal bands, and crazy-paving pattern in chest tomography	Number of participants with severe COVID pneumonia measured by the presence of ground-glass opacity, consolidations, parenchymal bands, and crazy-paving pattern in chest tomography	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of C-Reactive Protein (CRP) from baseline to 7, 14 and 21 days	Levels of C-Reactive Protein (CRP) from baseline to 7, 14 and 21 days	1,7,14 and 21 days
Total white blood count (1000 per mm³) from baseline to 7, 14 and 21 days	Total white blood count (1000 per mm³) from baseline to 7, 14 and 21 days	1,7,14 and 21 days
Levels of plasma ACE1 and ACE2 receptors from baseline to 7, 14 and 21 days	Levels of plasma ACE1 and ACE2 receptors from baseline to 7, 14 and 21 days	1, 7, 14 and 21 days
ACE1/ACE2 ratio from baseline to 7, 14 and 21 days days until the end of the study of each cohort	ACE1/ACE2 ratio from baseline to 7, 14 and 21 days days until the end of the study of each cohort	1, 7, 14 and 21 days
ACE1, ACE2, TMPRSS2 and furin gene expression levels from baseline to 21 days placebo in each cohort	ACE1, ACE2, TMPRSS2 and furin gene expression levels from baseline to 21 days	1 and 21 days
Presence of presence of ground-glass opacity, consolidations, parenchymal bands, and crazy-paving pattern in chest tomography from baseline to 7, 14 and 21 days	Presence of presence of ground-glass opacity, consolidations, parenchymal bands, and crazy-paving pattern in chest tomography from baseline to 7, 14 and 21 days	1, 7, 14 and 21 days
Levels of inflammatory cytokines IL-6, IL-2, IL-7, IL-10,granulocyte-colony stimulating factor (GM-CSF), interferon-γ (IFN-γ) and Tumor Necrosis Factor (TNF-α) from baseline to 7, 14 and 21 days	Levels of inflammatory cytokines IL-6, IL-2, IL-7, IL-10,granulocyte-colony stimulating factor (GM-CSF), interferon-γ (IFN-γ) and Tumor Necrosis Factor (TNF-α) from baseline to 7, 14 and 21 days	1,7,14 and 21 days
Levels of total white blood count (1000 per mm³) from baseline to 7, 14 and 21 days Days 1, 7, 14 and 21 days after the administration of supplement or placebo in each cohort	Levels of total white blood count (1000 per mm³) from baseline to 7, 14 and 21 days	1,7,14 and 21 days
Levels of hemoglobin count (g/dl) from baseline to 7, 14 and 21 days Days 1, 7, 14 and 21 days after the administration of supplement or placebo in each cohort	Levels of hemoglobin count (g/dl) from baseline to 7, 14 and 21 days	1,7,14 and 21 days
Total platelets count (1000 per mm³) from baseline to 7, 14 and 21 days Days 1, 7, 14 and 21 days after the administration of supplement or placebo in each cohort	Total platelets count (1000 per mm³) from baseline to 7, 14 and 21 days	1,7,14 and 21 days
Levels of fibrinogen (g/L) from baseline to 7, 14 and 21 days Days 1, 7, 14 and 21 days after the administration of supplement or placebo in	Levels of fibrinogen (g/L) from baseline to 7, 14 and 21 days	1,7,14 and 21 days
Levels of D-Dimer (µg/mL) from baseline to 7, 14 and 21 days	Levels of D-Dimer (µg/mL) from baseline to 7, 14 and 21 days	1,7,14 and 21 days
Levels of Ferritin (µg/mL) from baseline to 7, 14 and 21 days Days 1, 7, 14 and 21 days after the administration of supplement or placebo in each cohort	Levels of Ferritin (µg/mL) from baseline to 7, 14 and 21 days	1,7,14 and 21 days

Collaborators and Investigators

• Sponsor: SENAI CIMATEC
• Collaborators: Hospital Espanhol
• Investigators: Principal Investigator: Roberto Badaró, Ph.D, SENAI CIMATEC

Publications and helpful links

General Publications

• Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
• Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, Cuomo-Dannenburg G, Thompson H, Walker PGT, Fu H, Dighe A, Griffin JT, Baguelin M, Bhatia S, Boonyasiri A, Cori A, Cucunuba Z, FitzJohn R, Gaythorpe K, Green W, Hamlet A, Hinsley W, Laydon D, Nedjati-Gilani G, Riley S, van Elsland S, Volz E, Wang H, Wang Y, Xi X, Donnelly CA, Ghani AC, Ferguson NM. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020 Jun;20(6):669-677. doi: 10.1016/S1473-3099(20)30243-7. Epub 2020 Mar 30. Erratum In: Lancet Infect Dis. 2020 Apr 15;: Lancet Infect Dis. 2020 May 4;:
• Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5.
• FRITZ IB. Action of carnitine on long chain fatty acid oxidation by liver. Am J Physiol. 1959 Aug;197:297-304. doi: 10.1152/ajplegacy.1959.197.2.297. No abstract available.
• Brass EP. Pharmacokinetic considerations for the therapeutic use of carnitine in hemodialysis patients. Clin Ther. 1995 Mar-Apr;17(2):176-85; discussion 175. doi: 10.1016/0149-2918(95)80017-4.
• Kraemer WJ, Volek JS, Dunn-Lewis C. L-carnitine supplementation: influence upon physiological function. Curr Sports Med Rep. 2008 Jul-Aug;7(4):218-23. doi: 10.1249/JSR.0b013e318180735c.
• Ozturk MA, Kardas Z, Kardas F, Gunes T, Kurtoglu S. Effects of L-carnitine supplementation on respiratory distress syndrome development and prognosis in premature infants: A single blind randomized controlled trial. Exp Ther Med. 2016 Mar;11(3):1123-1127. doi: 10.3892/etm.2015.2964. Epub 2015 Dec 29.
• Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004 Jun;203(2):631-7. doi: 10.1002/path.1570.
• Ciaglia E, Vecchione C, Puca AA. COVID-19 Infection and Circulating ACE2 Levels: Protective Role in Women and Children. Front Pediatr. 2020 Apr 23;8:206. doi: 10.3389/fped.2020.00206. eCollection 2020. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): February 3, 2022

Study Registration Dates

• First Submitted: April 23, 2022
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 7, 2022

Study Record Updates

• Last Update Posted (Actual): July 7, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections
• Other Study ID Numbers: 01/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No