Effect of Pioglitazone on T2DM Patients With COVID-19

NCT04604223 | Unknown Phase 4

• 1 other identifier: RA HM-2020- 011
• Study Type: interventional
• Target: 1,506
• Locations: 2 countries
• Sites: 5

Brief Summary

Approximately 10-15% of patients infected with COVID-19 develop severe illness characterized by respiratory distress, increased risk of clotting disease, myocardial damage, stroke and mortality. Subjects with Type 2 diabetes (T2DM) are at increased risk for severe COVID-19 disease. Exuberant inflammatory and immune responses were suggested as the etiology responsible for the development of severe COVID-19 disease. The increased chronic inflammatory state characteristic of T2DM could contribute to the increased risk of severe COVID-19 disease in T2DM patients. Therefore, its possible that anti-inflammatory therapy will reduce the risk of severe COVID-19 disease. Consistent with this assumption, a recent study has reported that steroid therapy improves the outcome in patients with severe COVID-19 disease. The medication pioglitazone is a strong insulin sensitizer that reduces plasma glucose concentrations in T2DM patients. In addition to improving insulin sensitivity, several studies have demonstrated that pioglitazone reduces chronic inflammation in T2DM patients, which is manifested in a decrease in TNF-alpha, interleukin, hs CRP, leptin and other inflammatory markers in T2DM treated with pioglitazone. Further, pioglitazone enhances the plasma level of anti-inflammatory agents. For example, the plasma level of 15-epi-lipoxin A, a lipid mediator with strong anti-inflammatory and inflammation-resolving effects that has been reported to neutralize RNA coated viruses, is significantly elevated by pioglitazone treatment in T2DM patients. Therefore, we hypothesize that administering pioglitazone to T2DM patients who have moderate-to-severe COVID-19 will improve the clinical outcome of their COVID-19 disease.

Conditions

Covid19; Type 2 Diabetes

Outcome Measures

Primary Outcomes (2)

• HsCRP level

  Difference from baseline to 4 weeks in inflammatory response between subjects receiving pioglitazone versus placebo measured as plasma hsCRP level.

  4 weeks

• Difference in the incidence at 4 weeks of a composite outcome comprised of:

  1\) requirement for mechanical ventilation (invasive \[with tracheal tube\] or non-invasive); 2) myocardial damage measured as plasma troponin I level \> 3 times the upper normal limit; or 3) death.

  4 weeks

Secondary Outcomes (7)

• Number of days free of mechanical ventilation

  4 weeks

• Number of days in the ICU

  4 weeks

• Duration of hospitalization

  4 weeks

• Change from baseline in qSOFA score

  4 Weeks

• Change from baseline in SO2/FiO2

  4 Weeks

Study Arms (2)

Pioglitazone

EXPERIMENTAL

Pioglitazone will be started at 45 mg/day dose for 10 days, after 10 days, the dose will be reduced to 30 mg/day to minimize possible adverse events. The treatment will be continued for 4 weeks (28 days) total.

Drug: Pioglitazone 45 mg

Placebo

PLACEBO COMPARATOR

Placebo tablets at 45 mg/day will be given for 10 days, after 10 days, the tablets will be reduced to 30 mg/day. The treatment will be continued for 4 weeks (28 days) total.

Drug: Pioglitazone 45 mg

Interventions

Pioglitazone 45 mg DRUG

Pioglitazone will be started at 45 mg/day dose for 10 days, after 10 days, the dose will be reduced to 30 mg/day to minimize possible adverse events. The treatment will be continued for 4 weeks (28 days) total

Pioglitazone; Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• T2DM according to the ADA criteria. Patients with long standing diabetes as well as patients with new onset diabetes will be recruited. Patients receiving glucocorticoids for treatment of COVID-19 and manifest plasma glucose levels consistent with diabetes diagnosis also will be included
• Patients can be drug naïve, receiving oral antihyperglycemic therapy (except pioglitazone), GLP-1 RA or insulin therapy will be allowed to participate in the study
• COVID-19 infection confirmed with PCR test
• Age 21-85 years
• Patients of both sexes will be included
• In addition to diabetes and COVID-19 diagnoses, patients should manifest at least one of COVID-19 symptoms (Fever, Chills, Headache, Rhinorreah, Cough (dry or with sputum), Sore Throat, shortness of breath, Hemoptysis, Altered mentation, Fatigue/Malaise, Myalgia, Nausea/Vomiting, Diarrhea, Anosmia, Chest pain).
• Patient receiving other anti-inflammatory therapy for their routine COVID-19 care (e.g. hydroxychloroquine), or antiviral therapy (e.g. remdesivire) will be included in the study and will be evenly randomized amongst the two treatment groups

You may not qualify if:

• T1DM
• Absence of confirmation of COVID-19 infection
• Age \<21 years
• Presence of heart failure (LVEF\<40%) or a history of hospitalization for heart failure
• Use of diuretics (furosemide or aldactone) for heart disease usually for heart failure. Patients with hypertension receiving diuretic therapy (usually thiazide) will be included in the study
• Patient on mechanical ventilation or patients whose clinical condition requires mechanical ventilation in the following 24 hours.
• Patients not expected to survive \> 48 hours
• Patients receiving pioglitazone for the management of their diabetes
• Patients participating in other research study will be excluded
• Pregnant women will be excluded from the study

Sponsors & Collaborators

• Dasman Diabetes Institute: lead
• Ministry of Health, Kuwait: collaborator
• Texas Diabetes Institute: collaborator
• Kuwait University: collaborator

Study Sites (5)

Al-Amiri Hospital

Kuwait City, (Pick From List), 40000, Kuwait

RECRUITING

Jaber Al Ahmad Al Sabah Hospital

Kuwait City, (Pick From List), 40000, Kuwait

RECRUITING

Mishrif Field Hospital

Kuwait City, (Pick From List), 40000, Kuwait

RECRUITING

Mubarak Al-Kabeer Hospital

Kuwait City, (Pick From List), 40000, Kuwait

RECRUITING

Hamad Medical Corporation

Doha, Qatar

RECRUITING

Related Publications (1)

• Baagar K, Alessa T, Abu-Farha M, Abubaker J, Alhumaidi H, Franco Ceruto JA, Hamad MK, Omrani A, Abdelrahman S, Zaka-Ul Haq M, Safi AW, Alhariri B, Barman M, Abdelmajid A, Cancio HVD, Elmekaty E, Al-Khairi I, Cherian P, Jayyousi L, Ahmed M, Qaddoumi M, Hajji S, Esmaeel A, Al-Andaleeb A, Channanath A, Devarajan S, Ali H, Thanaraj TA, Al-Sabah S, Al-Mulla F, Abdul-Ghani M, Jayyousi A. Effect of pioglitazone on inflammatory response and clinical outcome in T2DM patients with COVID-19: a randomized multicenter double-blind clinical trial. Front Immunol. 2024 Sep 6;15:1369918. doi: 10.3389/fimmu.2024.1369918. eCollection 2024.

  PMID: 39308871 DERIVED

MeSH Terms

Conditions

COVID-19; Diabetes Mellitus, Type 2

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Fahd Al-Mulla, PhD

  Dasman Diabetes Institute

  PRINCIPAL INVESTIGATOR

• Thamer Alessa, MD

  Dasman Diabetes Institute. Ministry of Health, Kuwait

  PRINCIPAL INVESTIGATOR

• Mohamed Abu-farha

  Dasman Diabetes Institute

  PRINCIPAL INVESTIGATOR

• Muhammed Abdul-Ghani, MD/PhD

  Texas Diabetes Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohamed Abu-farha, PhD

CONTACT

96560660804; mohamed.abufarha@dasmaninstitute.org

Thamer Alessa, MD

CONTACT

96599877855; thamer.alessa@dasmaninstitute.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: October 27, 2020
• Study Start: January 18, 2021
• Primary Completion: June 29, 2021
• Study Completion: June 29, 2021
• Last Updated: March 17, 2021

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

QA (1); KU (4)