Metformin Glycinate, Treatment of Patients With COVID-19 and Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2.

Overview

The purpose of this study is to evaluate the efficacy and safety of the metformin glycinate and standard treatment of the hospital in hospitalized patients with Severe Acute Respiratory Syndrome secondary to SARS-CoV2.

Full Title of Study: “Adaptive Study to Demonstrate Efficacy and Safety of Metformin Glycinate for the Treatment of Hospitalized Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2. Randomized, Double-Blind, Phase IIIb”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: March 8, 2021

Detailed Description

After being informed about the study and potential risks, all patients giving written informed consent will undergo a 1 day screening period to determine eligibility for study entry. At day 0, patients who meet the eligibility requirements will be randomized in a double blind manner (participant and investigator) in a 1:1 ratio to metformin glycinate (620 mg, taken orally, twice daily) plus standard treatment or placebo (taken orally, twice daily) plus standard treatment, both for 14 days.

Interventions

  • Drug: Metformin Glycinate
    • Participants randomized to metformin glycinate will take 620 mg bid (PO) for 14 days plus standard treatment
  • Drug: Placebo oral tablet
    • Participants randomized to placebo will take a tablet bid (PO) for 14 days in plus standard treatment

Arms, Groups and Cohorts

  • Experimental: Metformin glycinate
    • 620 mg bid (PO) for 14 days plus standard treatment
  • Placebo Comparator: Placebo
    • Placebo tablet bid (PO) for 14 days plus standard treatment

Clinical Trial Outcome Measures

Primary Measures

  • Viral load
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Assess differences in SARS-CoV-2 viral load between participants that receive placebo vs metformin glycinate
  • consciousness level
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Clinical status assessed by measurement of consciousness level: alertness
  • temperature
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Clinical status assessed by measurement of axillary body temperature in °C: <37.2.
  • systolic blood pressure
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Clinical status assessed by measurement of systolic blood pressure in mmHg: >90.
  • Oxigen saturation
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Clinical status assessed by measurement of oxygen saturation in %: >90.
  • Heart rate
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Clinical status assessed by measurement of heart rate in beats per minute: <100 bpm.
  • respiratory rate
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Clinical status assessed by measurement of respiratory rate in breaths per minute: <24 bpm,
  • Days of hospitalization
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Assess length of hospitalization
  • Days of supplementary oxygen if applies
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Assess length of supplementary oxygen
  • Days of supplementary mechanical ventilation
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Assess length of mechanical ventilation

Secondary Measures

  • Toxicity of study drug assessed by incidence of adverse events (grade 3 or 4)
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Assess by incidence of Grade 3, Grade 4, and Serious Adverse Events (AEs)
  • Changes in laboratory test results
    • Time Frame: Day 0 to Day 28 or patient discharge day
    • Changes in serum levels from security laboratories compared to baseline levels and between groups.

Participating in This Clinical Trial

Inclusion Criteria

1. ≥ 18 years old 2. Ability to understand and the willingness to sign a written informed consent document before any study procedure 3. Coronavirus infection, severe acute respiratory syndrome (SARS-CoV)-2 confirmed by the polymerase chain reaction (PCR) test ≤ 4 days before randomization. 4. Hospitalized 5. Radiographic evidence of pulmonary infiltrates Exclusion Criteria:

1. Participation in any other clinical trial of an experimental treatment for COVID-19 2. Evidence of multi-organ failure 3. Require mechanical ventilation before randomization 4. Pregnant patients 5. Patients with kidney failure, cancer and among other conditions that due to their treatment and / or baseline condition, affect the distribution, bioavailability and elimination of the studied drug

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Laboratorios Silanes S.A. de C.V.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Janet Silvia M Aguirre, MD, Principal Investigator, The American British Cowdray Medical Center. I.A.P.

References

Fischer M, Timper K, Radimerski T, Dembinski K, Frey DM, Zulewski H, Keller U, Müller B, Christ-Crain M, Grisouard J. Metformin induces glucose uptake in human preadipocyte-derived adipocytes from various fat depots. Diabetes Obes Metab. 2010 Apr;12(4):356-9. doi: 10.1111/j.1463-1326.2009.01169.x.

Cuthbertson J, Patterson S, O'Harte FP, Bell PM. Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in Type 2 diabetes. Diabet Med. 2009 Jun;26(6):649-54. doi: 10.1111/j.1464-5491.2009.02748.x.

Citations Reporting on Results

Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, Rooyackers O, Zhou G, Williamson JM, Ljunqvist O, Efendic S, Moller DE, Thorell A, Goodyear LJ. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 2002 Jul;51(7):2074-81.

Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, Montminy M, Cantley LC. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005 Dec 9;310(5754):1642-6. Epub 2005 Nov 24.

Detaille D, Guigas B, Leverve X, Wiernsperger N, Devos P. Obligatory role of membrane events in the regulatory effect of metformin on the respiratory chain function. Biochem Pharmacol. 2002 Apr 1;63(7):1259-72.

Tamura Y, Watada H, Sato F, Kumashiro N, Sakurai Y, Hirose T, Tanaka Y, Kawamori R. Effects of metformin on peripheral insulin sensitivity and intracellular lipid contents in muscle and liver of overweight Japanese subjects. Diabetes Obes Metab. 2008 Sep;10(9):733-8. Epub 2007 Oct 15.

Standeven KF, Ariëns RA, Whitaker P, Ashcroft AE, Weisel JW, Grant PJ. The effect of dimethylbiguanide on thrombin activity, FXIII activation, fibrin polymerization, and fibrin clot formation. Diabetes. 2002 Jan;51(1):189-97.

González-Ortiz M, Martínez-Abundis E, Robles-Cervantes JA, Ramos-Zavala MG, Barrera-Durán C, González-Canudas J. Efficacy and Safety of Metformin Glycinate vs. Metformin Hydrochloride in Metabolic Control and Inflammatory Mediators in Type 2 Diabetes Mellitus Patients (T2DM). Diabetes Technol Ther. 2012 Dec;14(12):1140-4. Diabetes Technol Ther. 2012 Dec;14(12):1140-4. doi: 10.1089/dia.2012.0097

Jorge González Canudas, COMET GROUP Diabetes Efficacy and Safety of Metformin Glycinate vs. Metformin Hydrochloride in Metabolic Control and Inflammatory Mediators in Type 2 Diabetes Mellitus Patients. Diabetes 2019 Jun; 68(Supplement 1)

Garza-Ocañas L, Tamez-de la O E, Iglesias-Chiesa J, Gonzalez Canudas J, Rivas-Ruiz R: Pharmacokinetics and gastrointestinal tolerability of DMMET 01 (glycinate of metformin): results of a prospective randomized trial in healthy volunteers [abstract]. Diabetes 2009;58(Suppl 1):A533

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.