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

• ClinicalTrials.gov Identifier: NCT05446961
• Recruitment Status: Completed
• First Posted: July 7, 2022
• Last Update Posted: July 7, 2022
• Sponsor: SENAI CIMATEC
• Collaborator: Hospital Espanhol
• Information provided by (Responsible Party): SENAI CIMATEC

Tracking Information

• First Submitted Date: April 23, 2022
• First Posted Date: July 7, 2022
• Last Update Posted Date: July 7, 2022
• Actual Study Start Date: March 1, 2021
• Actual Primary Completion Date: September 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2022)

• Number new SARS-CoV-2 cases at 21 days assessed by RT-PCR [ Time Frame: 21 days ]
  Number new SARS-CoV-2 cases at 21 days assessed by RT-PCR
• 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 [ Time Frame: 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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: June 30, 2022)

• Levels of C-Reactive Protein (CRP) from baseline to 7, 14 and 21 days [ Time Frame: 1,7,14 and 21 days ]
  Levels of C-Reactive Protein (CRP) from baseline to 7, 14 and 21 days
• Total white blood count (1000 per mm³) from baseline to 7, 14 and 21 days [ Time Frame: 1,7,14 and 21 days ]
  Total white blood count (1000 per mm³) from baseline to 7, 14 and 21 days
• Levels of plasma ACE1 and ACE2 receptors from baseline to 7, 14 and 21 days [ Time Frame: 1, 7, 14 and 21 days ]
  Levels of plasma ACE1 and ACE2 receptors from baseline to 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 [ Time Frame: 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, TMPRSS2 and furin gene expression levels from baseline to 21 days placebo in each cohort [ Time Frame: 1 and 21 days ]
  ACE1, ACE2, TMPRSS2 and furin gene expression levels from baseline to 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 [ Time Frame: 1, 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
• 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 [ Time Frame: 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 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 [ Time Frame: 1,7,14 and 21 days ]
  Levels of total white blood count (1000 per mm³) from baseline to 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 [ Time Frame: 1,7,14 and 21 days ]
  Levels of hemoglobin count (g/dl) from baseline to 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 [ Time Frame: 1,7,14 and 21 days ]
  Total platelets count (1000 per mm³) from baseline to 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 [ Time Frame: 1,7,14 and 21 days ]
  Levels of fibrinogen (g/L) from baseline to 7, 14 and 21 days
• Levels of D-Dimer (µg/mL) from baseline to 7, 14 and 21 days [ Time Frame: 1,7,14 and 21 days ]
  Levels of D-Dimer (µg/mL) from baseline to 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 [ Time Frame: 1,7,14 and 21 days ]
  Levels of Ferritin (µg/mL) from baseline to 7, 14 and 21 days

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Study to Evaluate the Effect of Food Supplement in People Infected With Coronavirus
• Official Title: 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)
• Brief Summary: 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

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
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description:

A total of 274 subjects, will be prospectively enrolled into a pilot randomized, placebo controlled study in the two cohorts: Cohort 1: 220 healthy, SARS-CoV-2 negative, individuals (55 to 85 years old) with close contact (cohabit) to a person with newly acquired SARS-CoV-2 infection based on PCR detection and absence of antibody response; and, Cohort 2: 54 asymptomatic ( 18 to 85 years old) or symptomatic patients with mild COVID-19 that tested positive for COVID-19 by RT-PCR within the last 24 hours prior to the enrolment in the study.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The groups will be randomized and blindly assigned to receive either the LCLT supplement (3 g per day that delivers 2 g elemental of L-carnitine) or placebo. Subjects from Cohort 2 will receive L-carnitine in addition to Standard of Care (SOC) therapy or placebo in addition tosStandard of care (SOC) therapy

Primary Purpose: Treatment

• Condition: COVID-19 Virus Infection

Intervention

• Dietary Supplement: LCLT : 68% elemental L-carnitine and 32 % Tartric acid
  3 g orally capsules
  Other Name: Carnipure™ Tartrate (LCLT) formulation
• Drug: Placebo
  orally capsules

Study Arms

• 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
  Intervention: Dietary Supplement: LCLT : 68% elemental L-carnitine and 32 % Tartric acid
• 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
  Intervention: Drug: Placebo
• 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
  Intervention: Dietary Supplement: LCLT : 68% elemental L-carnitine and 32 % Tartric acid
• 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
  Intervention: Drug: Placebo

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.
• 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.
• 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;:
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 30, 2022): 224
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: February 3, 2022
• Actual Primary Completion Date: September 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT05446961
• Other Study ID Numbers: 01/2021
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: SENAI CIMATEC
• Original Responsible Party: Same as current
• Current Study Sponsor: SENAI CIMATEC
• Original Study Sponsor: Same as current
• Collaborators: Hospital Espanhol

Investigators

• Principal Investigator: Roberto Badaró, Ph.D; SENAI CIMATEC

• PRS Account: SENAI CIMATEC
• Verification Date: June 2022