Clinical Trial of Pioglitazone Treatment in Patients With Type 2 Diabetes Mellitus and Covid-19

• ClinicalTrials.gov Identifier: NCT04535700
• Recruitment Status: Recruiting
• First Posted: September 2, 2020
• Last Update Posted: November 17, 2020
• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Information provided by (Responsible Party): Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Study Description

Brief Summary:

The treatment with pioglitazone added to the standard treatment of patients with DM2 hospitalized for COVID-19 may produce a decrease in the number of patients who progress to a second phase of severe systemic inflammation.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes	Drug: Pioglitazone 30 mg; Other: standard of care	Phase 4

Detailed Description:

According to the latest studies, the evolution of the SARS-CoV-2 (COVID-19) infection shows two clinically different phases: The first phase of viral and clinical infection of viriasis (fever, myalgia, etc.) affects all patients and it is resolved in asymptomatic patients or with clinically moderate-mild affectations. However, towards the end of the first week of illness, a not inconsiderable number of patients progress towards a second phase of rapid and abrupt deterioration of their respiratory and cardiac function.

More and more data indicate an important role of overactivated macrophages, interleukin 6 (IL6) and an excessive inflammatory response in the genesis of this second phase of aggravation. Linking with this hypothesis, the adipose tissue densely infiltrated by macrophages is the source of one third of the body's IL6, its production being even greater in the fat of central disposition of male distribution. All of this could explain the worse prognosis observed in men, obese and with type 2 diabetes (DM2).

Regarding the possible effect of pioglitazone on the expression of ACE2, there is little literature, and less evidence, about the response of this receptor to treatment with pioglitazone, and what is more important, its effect on COVID-19 infection.

Two studies have analyzed the expression of this receptor after administration of pioglitazone in different murine models of liver and kidney disease. The conclusions of these studies were that the administration of pioglitazone in rats with hepatic steatosis increased the expression of ACE2. It is known that the increased expression of ACE2 facilitates the entry of SARS-CoV-2 into the cell, in animal models it has been seen that ACE2 protects against the development of respiratory distress syndrome and that severe cases of COVID-19 and SARS 2003 have been linked to the possible inhibition of ACE2 by the virus and the increase in angiotensin II.

In conclusion, it is a safe and proven drug in patients with DM2, cheap, with years of clinical experience. The use of pioglitazone added to the conventional treatment of patients at high risk, such as patients with COVID-19 and DM2, could be accompanied by a better evolution of the patients, avoiding or mitigating the inflammatory process that already occurs before its onset. seems to trigger the second accelerated phase of the disease.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Non-blinded, Randomized and Controlled Clinical Trial of Pioglitazone Treatment in Patients With Type 2 Diabetes Mellitus and Covid-19
• Actual Study Start Date: September 18, 2020
• Estimated Primary Completion Date: March 10, 2021
• Estimated Study Completion Date: April 10, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: pioglitazone	Drug: Pioglitazone 30 mg; Patients receive 30 mg/day of pioglitazone for the entire period they remain in hospital
Standard of care treatment	Other: standard of care; Patients receive the standard of care, according to the hospital protocol for patients with type 2 diabetes mellitus hospitalized.

Outcome Measures

Primary Outcome Measures :

1. Patients treated with pioglitazone, together with conventional treatment for COVID-19 infection, who during their admission evolve towards the need to receive support with mechanical ventilation, enter the ICU and / or die. [ Time Frame: Through hospitalization period, an average of 10-20 days until hospital discharge ]
   Number of patients receive pioglitazone treatment during their hospital stay who receive support with mechanical ventilation, enter the ICU and / or die.

Secondary Outcome Measures :

1. Incidence of pioglitazone treatment-Emergent Adverse Events in patients with DM2 and symptomatic SARS-CoV-2 infection. [ Time Frame: Everyday through hospitalization period, an average of 10-20 days until hospital discharge ]
   Proportion of patients who develop heart failure or adverse reaction associated with treatment.
2. Biomarker analysis: systemic inflammation parameters during the administration of pioglitazone treatment. [ Time Frame: Each 48 hours through hospitalization period, an average of 10-20 days until hospital discharge ]
   Changes in this inflammation parameter: C-reactive protein (in mg/dl)
3. Biomarker analysis: systemic inflammation parameters during the administration of pioglitazone treatment. [ Time Frame: Each 48 hours through hospitalization period, an average of 10-20 days until hospital discharge ]
   Changes in this inflammation parameter: D-dimer (in μg/mL)
4. Biomarker analysis: systemic inflammation parameters during the administration of pioglitazone treatment. [ Time Frame: Each 48 hours through hospitalization period, an average of 10-20 days until hospital discharge ]
   Changes in this inflammation parameter: ferritin (in ng/mL)
5. Biomarker analysis: systemic inflammation parameters during the administration of pioglitazone treatment. [ Time Frame: Each 48 hours through hospitalization period, an average of 10-20 days until hospital discharge ]
   Changes in this inflammation parameter: creatine kinase (CK) (in mg/dL)
6. Biomarker analysis: systemic inflammation parameters during the administration of pioglitazone treatment. [ Time Frame: Each 48 hours through hospitalization period, an average of 10-20 days until hospital discharge ]
   Changes in this inflammation parameter: number of lymphocytes (in μL)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Adult patients > 18 years
2. Confirmed diagnosis of COVID-19 or high clinical suspicion according to current criteria.
3. Diagnosis prior to admission of DM2.
4. Patients who provide their informed consent to participate in the study

Exclusion Criteria:

1. Under 18 years
2. Known hypersensitivity to the active ingredient or any of the drug's excipients.
3. Known history of heart failure or situation at the time of initiation of the heart failure study.
4. Hepatic failure.
5. Dialysis
6. Situation of diabetic ketoacidosis at the start of the study.
7. Diabetes mellitus different from type 2.
8. Active bladder cancer or a history of bladder cancer
9. Hematuria
10. Patients included in another experimental study with another drug.
11. Admission to the Intensive Care Unit.
12. Patients requiring mechanical ventilation at the time of inclusion
13. Pregnancy
14. Lactation

Contacts and Locations

Contacts

Contact: Jesús Marceliano Gómez Martín, Phd; +34 91336800 ext 8726; jesusmarceliano.gomez@salud.madrid.org

Locations

Spain

Hospital Ramón y Cajal; Recruiting

Madrid, Spain, 28034

Contact: Jesús M. Gómez, PhD +3491336800 ext 8726 jesusmarceliano.gomez@salud.madrid.org

Sponsors and Collaborators

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

More Information

• Responsible Party: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• ClinicalTrials.gov Identifier: NCT04535700
• Other Study ID Numbers: ESCORPIO
• First Posted: September 2, 2020
• Last Update Posted: November 17, 2020
• Last Verified: November 2020

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

Keywords provided by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal:

pioglitazone; Covid19

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pioglitazone; Hypoglycemic Agents; Physiological Effects of Drugs