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

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

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.

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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

Resource links provided by the National Library of Medicine


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.




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)



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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04535700


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

Locations
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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
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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    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: November 2020

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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:
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COVID-19
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs