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

Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Trial

— DMMETCOV19-2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04625985
• Other study ID #: SIL-30000-II-20(2)
• Status: Completed
• Phase: Phase 2
• Start date: July 14, 2020
• Est. completion date: March 18, 2021

Study information

• Verified date: April 2021
• Source: Laboratorios Silanes S.A. de C.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 18, 2021
• Est. primary completion date: March 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Infections
• Severe Acute Respiratory Syndrome
• Severe Acute Respiratory Syndrome Coronavirus 2
• Syndrome

Intervention

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

Locations

Country	Name	City	State
Mexico	The American British Cowdray Medical Center, I.A.P	Mexico City

Sponsors (1)

Lead Sponsor	Collaborator
Laboratorios Silanes S.A. de C.V.

Country where clinical trial is conducted

Mexico, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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]. Diab

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 Mell

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)

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 d — View Citation

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. — View Citation

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. — View Citation

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; — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Viral load	Assess differences in SARS-CoV-2 viral load between participants that receive placebo vs metformin glycinate	Day 0 to Day 28 or patient discharge day
Primary	consciousness level	Clinical status assessed by measurement of consciousness level: alertness	Day 0 to Day 28 or patient discharge day
Primary	temperature	Clinical status assessed by measurement of axillary body temperature in °C: <37.2.	Day 0 to Day 28 or patient discharge day
Primary	systolic blood pressure	Clinical status assessed by measurement of systolic blood pressure in mmHg: >90.	Day 0 to Day 28 or patient discharge day
Primary	Oxigen saturation	Clinical status assessed by measurement of oxygen saturation in %: >90.	Day 0 to Day 28 or patient discharge day
Primary	Heart rate	Clinical status assessed by measurement of heart rate in beats per minute: <100 bpm.	Day 0 to Day 28 or patient discharge day
Primary	respiratory rate	Clinical status assessed by measurement of respiratory rate in breaths per minute: <24 bpm,	Day 0 to Day 28 or patient discharge day
Primary	Days of hospitalization	Assess length of hospitalization	Day 0 to Day 28 or patient discharge day
Primary	Days of supplementary oxygen if applies	Assess length of supplementary oxygen	Day 0 to Day 28 or patient discharge day
Primary	Days of supplementary mechanical ventilation	Assess length of mechanical ventilation	Day 0 to Day 28 or patient discharge day
Secondary	Toxicity of study drug assessed by incidence of adverse events (grade 3 or 4)	Assess by incidence of Grade 3, Grade 4, and Serious Adverse Events (AEs)	Day 0 to Day 28 or patient discharge day
Secondary	Changes in laboratory test results	Changes in serum levels from security laboratories compared to baseline levels and between groups.	Day 0 to Day 28 or patient discharge day