Covid19Phase 3SIDIACONCT04365517
The Effect of Sitagliptin Treatment in COVID-19 Positive Diabetic Patients
A Phase 3 study testing Sitagliptin in people with Covid19 and Diabetes Mellitus, Type 2, run by University of Milan at 1 site in Italy.
Trial summary
The COVID-19 pathology is frequently associated with diabetes mellitus and metabolic syndrome. In the epidemic outbreak that exploded at the beginning of 2020 in the Lombardy Region, about two thirds of the patients who died from COVID-19 were affected by diabetes mellitus. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, Diabetes Mellitus, Type 2, CKD
- What is being tested?
- Sitagliptin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 1 siteItaly
- Study dates
- 29 Dec 2021to 30 Dec 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of type 2 diabetes, according to ADA 2020 criteria
- HbA1c levels at the entrance or in the two previous months <9%
- Diagnosis of Covid-19 (swab for positive SARS-COV2 RNA) with pneumonia, with or without increase in inflammation indexes, with or without respiratory failure
- No indication for tocilizumab therapy (BCRSS, Brescia Covid Respiratory Severity Scale, <3).
- Written and dated informed consent from the patient or his legally valid representative
Who cannot join
- Pregnancy
- Type 1 diabetes
- Stage IV and V renal failure (stimated glomerular filtration rate <30 ml / min)
- Treatment with Dipeptidyl peptidase-4 inhibitors or GLP-1 Receptor Agonists in the month prior to hospitalization
- Pioglitazone treatment in the month prior to hospitalization
- Treatment in the month preceding or in the course of hospitalization with "biological" drugs for immuno-rheumatological diseases (in particular tocilizumab)
Show all 15Show fewer
- Presence of other acute or chronic ongoing infections
- Neurological or psychiatric diseases, diagnosis of hemoglobinopathy, diagnosis of liver disease, cancer, cystic fibrosis or malabsorption syndrome
- Dysphagia with need for artificial nutrition
- Positive history of acute and chronic pancreatitis
- Unstable cardiovascular disease or known atherosclerotic disease
- A history of alcohol or drug abuse
- Known human immunodeficiency virus (HIV) or hepatitis
- Presence of serious diseases or conditions that make the patient unsuitable for the study
- Surgery in the previous two weeks
Trial locations and contacts
1 site in 1 country.
Italy1 site
ASST FBF Sacco
Milan, 20157
Teresa Letizia, Dr., 02 39042648, letizia.teresa@asst-fbf-sacco.it
Paolo Fiorina, MD, PhD
About this study
The COVID-19 pathology is frequently associated with diabetes mellitus and metabolic syndrome. In the epidemic outbreak that exploded at the beginning of 2020 in the Lombardy Region, about two thirds of the patients who died from COVID-19 were affected by diabetes mellitus. COVID-19 occurs in 70% of cases with an inflammatory pathology of the airways that can be fed by a cytokine storm and result in severe respiratory failure (10% cases) and death (5%). The pathophysiological molecular mechanisms are currently not clearly defined. It is hypothesized that the transmembrane glycoprotein type II CD26, known for the enzyme activity Dipeptilpeptidase 4 of the extracellular domain, may play a main role in this condition. It is in fact considerably expressed at the level of parenchyma and pulmonary interstitium and carries out both systemic and paracrine enzymatic activity, modulating the function of various proinflammatory cytokines, growth factors and vasoactive peptides in the deep respiratory tract. Of particular interest is the fact that Dipeptilpeptidase 4 has been identified as a cellular receptor for S glycoprotein of MERS-COV. In the case of the SARS-COV 2 virus, the main receptor is the Angiotensin-Converting Enzyme 2 protein, but a possible interaction with Dipeptilpeptidase 4 also cannot be excluded. The selective blockade of Dipeptilpeptidase 4 could therefore favorably modulate the pulmonary inflammatory response in the subject affected by COVID-19. This protein is also known for the enzymatic degradation function of the native glucagon-like peptide 1, one of the main regulators of insulin secretion. This is why it is a molecular target in the treatment of diabetes (drugs that selectively inhibit Dipeptilpeptidase 4 are marketed with an indication for the treatment of type 2 diabetes). It is believed that the use of a Dipeptilpeptidase 4 inhibitor in people with diabetes and hospitalized for Covid-19 may be safe and of particular interest for an evaluation of the effects on laboratory and instrumental indicators of inflammatory lung disease. Among the drugs that selectively block Dipeptilpeptidase 4, the one with the greatest affinity is Sitagliptin.
Read the detailed description
The investigators propose a randomized controlled open label intervention study. Patients hospitalized for COVID-19 and affected by type 2 diabetes mellitus will be included in the study and divided into two groups by randomization: sitagliptin add-on standard of care therapy with nutritional therapy with or without insulin treatment (study group) vs nutritional therapy with or without insulin treatment (group of control, standard therapy). The design of the study provides an open randomization to allow its feasibility in times compatible with the achievement of adequate cases during the epidemic. The presence of placebo and a double-blind study, would lead to longer planning and enrollment times.
Patients with type 2 diabetes mellitus hospitalized for COVID-19 and randomized to the study group will be treated with sitagliptin at an adjusted dosage for estimated glomerular filtrate: 100 mg once daily (estimated glomerular filtration rate less than or equal to 45 mL / min / 1.73 m2) or 50 mg (estimated glomerular filtration rate 30-45 mL / min / 1.73 m2) in combination or not with insulin treatment. Patients with stage IV and V renal impairment (estimated glomerular filtration rate less than or equal to 30 mL / min / 1.73 m2) will be excluded. Enrolled patients will be followed according to the following scheme:
Time points:
- T0: The doctor explains the protocol to the patient and he gives to him the informed consent and the letter to the general practitioner.
- T1: The patient gives the signed and dated consent and officially enters the study. Basic assessments will be made. At the baseline, the clinical response, the main laboratory and instrumental tests will be taken into consideration. Biological samples will be taken for immunological study. Diabetic patients will begin treatment with Sitagliptin 100 or 50 mg add-on to nutritional therapy and, eventually, insulin treatment. Any other hypoglycemic agents taken before admission will be suspended.
- T2: 7 days after T1, for both groups of patients, evaluation of the clinical response, of the average daily blood glucose levels, of the main laboratory and instrumental tests.
- T3: 10 days after T2, for both groups of patients, evaluation of clinical response, average daily blood glucose levels, of the main laboratory and instrumental tests. Collection of biological samples for immunological study. End of the study.
- Conditions
- Covid19, Diabetes Mellitus, Type 2, CKD
- Being tested
- Sitagliptin
- Medical subject headings
- COVID-19, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitagliptinDrug
We propose a randomized controlled open label intervention study. Patients with type 2 diabetes admitted to COVID-19 and randomized to the study group will be treated with sitagliptin at an adjusted dosage for estimated glomerular filtrate: 100 mg once daily (estimated glomerular filtration rate less than or equal to 45 mL / min / 1.73 m2 ) or 50 mg (estimated glomerular filtration rate 30-45 mL / min / 1.73 m2) in combination or not with insulin. Patients with stage IV and V renal failure (estimated glomerular filtration rate less than or equal to 30 mL / min / 1.73 m2) will be excluded
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Active comparator | patients will be treated with sitagliptin add on to nutritional therapy with o without insulin treatment. The dose of sitagliptin will be established on the basis of the estimated glomerular filtrate: 100 mg in single daily administration (estimated glomerular filtration rate less than or equal to 45 mL / min / 1.73 m2) or 50 mg (estimated glomerular filtration rate 30-45 mL / min / 1.73 m2) in combination or not with insulin. Patients with stage IV and V renal failure (estimated glomerular filtration rate less than or equal to 30 mL / min / 1.73 m2) will be excluded Receives: Drug: Sitagliptin |
| Control group | No intervention | Patients who will be prescribed nutritional therapy with or without insulin treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time for clinical improvement
Evaluation of the time between randomization and two-point improvement on a seven-category scale (1, not hospitalized, return to normal activities; 2, not hospitalized, but unable to return to normal activities; 3, hospitalized without the need for oxygen therapy; 4, hospitalized, need for oxygen therapy; 5, hospitalized, need for non-invasive ventilatory support; 6, hospitalized, need for invasive mechanical ventilation or Extra Corporeal Membrane Oxygenation; 7, death)
Measured: 1 month
Clinical parameter of acute lung disease
Clinical evaluation of the physiological parameter "cough" associated with acute lung disease from the start of the study to the end of the study.
Measured: 1 month
Biochemical parameter of acute lung disease
Variation of biochemical parameter "glycemia" of acute lung disease from the beginning of the study to the end of study.
Measured: 1 month
Clinical parameter of acute lung disease
Variation of the clinical parameter "oxygen saturation by the use of a pulse oximeter" of acute lung disease from the beginning of the study to the end of the study.
Measured: 1 month
Clinical parameter of acute lung disease
Variation of the clinical parameter "body temperature" of acute lung disease from the beginning of the study to the end of the study.
Measured: 1 month
Clinical parameter of acute lung disease
Variation of the clinical parameter "respiratory rate" of acute lung disease from the beginning of the study to the end of the study.
Measured: 1 month
Clinical parameter of acute lung disease
Variation of the clinical parameter "need for ventilatory support" of acute lung disease from the beginning of the study to the end of the study.
Measured: 1 month
Clinical parameters of acute lung disease
Variation of the clinical parameters "duration in days of ventilatory support, duration in days of oxygen therapy, duration in days of hospitalization, duration in days in the Intensive Care Unit, total length of stay in hospital" of acute lung disease from the beginning of the study to the end of the study.
Measured: 1 month
Clinical parameter of acute lung disease
Variation of the clinical parameter "blood gas analysis" of acute lung disease from the beginning of the study to the end of the study.
Measured: 1 month
Clinical parameter of acute lung disease
Variation of the clinical parameter "chest X ray" of acute lung disease from the beginning of the study to the end of the study.
Measured: 1 month
Clinical parameter of acute lung disease
Variation of the clinical parameter "PaO2/FiO2 ratio" of acute lung disease from the beginning of the study to the end of the study.
Measured: 1 month
Biochemical parameter of acute lung disease
Variation of biochemical parameter "reactive C protein" of acute lung disease from the beginning of the study to the end of study.
Measured: 1 month
Biochemical parameter of acute lung disease
Variation of biochemical parameter "blood count with formula" of acute lung disease from the beginning of the study to the end of study.
Measured: 1 month
Biochemical parameter of acute lung disease
Variation of biochemical parameter "erythrocyte sedimentation rate" of acute lung disease from the beginning of the study to the end of study.
Measured: 1 month
Biochemical parameter of acute lung disease
Variation of biochemical parameter "blood gas analysis" of acute lung disease from the beginning of the study to the end of study.
Measured: 1 month
Biochemical parameter of acute lung disease
Variation of biochemical parameter "LDH" of acute lung disease from the beginning of the study to the end of study.
Measured: 1 month
Secondary outcomes (9)
Dipeptilpeptidase 4 expression in biological samples
The alteration of Dipeptilpeptidase 4 expression will be evaluated in the collected biological samples
Measured: 6 months
Cytokine-inflammatory profile
Evaluation of inflammatory cytokines IL-2 and IL-7 in biological samples of treated patients and control group patients during infection.
Measured: 6 months
Glycemic variability
Effect on glycemic variability by evaluating HbA1c levels.
Measured: 1 month
Glycemic variability
Effect on glycemic variability by evaluating the average daily blood glucose levels.
Measured: 1 month
Cytokine-inflammatory profile
Evaluation of the inflammatory cytokine granulocyte-colony stimulating factor in biological samples of treated patients and control group patients during infection.
Measured: 6 months
Cytokine-inflammatory profile
Evaluation of the inflammatory cytokine interferon-γ inducible protein 10 in biological samples of treated patients and control group patients during infection.
Measured: 6 months
Cytokine-inflammatory profile
Evaluation of the inflammatory cytokine monocyte chemoattractant protein 1 in biological samples of treated patients and control group patients during infection.
Measured: 6 months
Cytokine-inflammatory profile
Evaluation of the inflammatory cytokine macrophage inflammatory protein 1-α in biological samples of treated patients and control group patients during infection.
Measured: 6 months
Cytokine-inflammatory profile
Evaluation of the inflammatory cytokine tumour necrosis factor-α in biological samples of treated patients and control group patients during infection.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2020
- Study start29 Dec 2021 (estimated)
- Primary completion30 Mar 2022 (estimated)
- Study completion30 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized controlled open label intervention study is proposed. Patients hospitalized for COVID-19 and suffering from type 2 diabetes will be included in the study and divided into two groups by randomization: sitagliptin add-on therapy with nutritional therapy with or without insulin (study group) vs nutritional therapy with or without insulin (group of control, standard therapy)
- Masking
- None (open label)
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paolo Fiorina, MD, University of Milan
- Investigators
- Paolo Fiorina, MD, PhD, Principal investigator, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04365517
- Sponsor's protocol ID
- Sacco FBF
- Acronym
- SIDIACO
- Status last verified
- Sep 2021
- First submitted
- 14 Apr 2020
- Last updated
- 28 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yang JK, Feng Y, Yuan MY, Yuan SY, Fu HJ, Wu BY, Sun GZ, Yang GR, Zhang XL, Wang L, Xu X, Xu XP, Chan JC. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006 Jun;23(6):623-8. doi: 10.1111/j.1464-5491.2006.01861.x.
PubMed 16759303Perlman S, Azhar EI, Memish ZA, Hui DS, Zumla A. Confronting the persisting threat of the Middle East respiratory syndrome to global health security. Lancet Infect Dis. 2020 Feb;20(2):158-160. doi: 10.1016/S1473-3099(19)30347-0. Epub 2019 Jul 3. No abstract available.
PubMed 31279728Remuzzi A, Remuzzi G. COVID-19 and Italy: what next? Lancet. 2020 Apr 11;395(10231):1225-1228. doi: 10.1016/S0140-6736(20)30627-9. Epub 2020 Mar 13.
PubMed 32178769Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
PubMed 32105632Zou H, Zhu N, Li S. The emerging role of dipeptidyl-peptidase-4 as a therapeutic target in lung disease. Expert Opin Ther Targets. 2020 Feb;24(2):147-153. doi: 10.1080/14728222.2020.1721468. Epub 2020 Jan 31.
PubMed 31971463Meyerholz DK, Lambertz AM, McCray PB Jr. Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract: Implications for the Middle East Respiratory Syndrome. Am J Pathol. 2016 Jan;186(1):78-86. doi: 10.1016/j.ajpath.2015.09.014. Epub 2015 Nov 18.
PubMed 26597880Ikeda T, Kumagai E, Iwata S, Yamakawa A. Soluble CD26/Dipeptidyl Peptidase IV Enhances the Transcription of IL-6 and TNF-alpha in THP-1 Cells and Monocytes. PLoS One. 2013 Jun 21;8(6):e66520. doi: 10.1371/journal.pone.0066520. Print 2013.
PubMed 23805228Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013 Mar 14;495(7440):251-4. doi: 10.1038/nature12005.
PubMed 23486063Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020 Apr;46(4):586-590. doi: 10.1007/s00134-020-05985-9. Epub 2020 Mar 3. No abstract available.
PubMed 32125455Vankadari N, Wilce JA. Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerg Microbes Infect. 2020 Mar 17;9(1):601-604. doi: 10.1080/22221751.2020.1739565. eCollection 2020.
PubMed 32178593Kulcsar KA, Coleman CM, Beck SE, Frieman MB. Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection. JCI Insight. 2019 Oct 17;4(20):e131774. doi: 10.1172/jci.insight.131774.
PubMed 31550243Li K, Wohlford-Lenane CL, Channappanavar R, Park JE, Earnest JT, Bair TB, Bates AM, Brogden KA, Flaherty HA, Gallagher T, Meyerholz DK, Perlman S, McCray PB Jr. Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice. Proc Natl Acad Sci U S A. 2017 Apr 11;114(15):E3119-E3128. doi: 10.1073/pnas.1619109114. Epub 2017 Mar 27.
PubMed 28348219
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Sitagliptin Treatment in COVID-19 Positive Diabetic Patients
- ClinicalTrials.gov ID
- NCT04365517
- Acronym / sponsor ID
- SIDIACO / Sacco FBF
- Conditions
- Covid19, Diabetes Mellitus, Type 2, CKD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 170 participants (estimated)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Study start
- 29 Dec 2021 (estimated)
- Primary completion
- 30 Mar 2022 (estimated)
- Study completion
- 30 Dec 2022 (estimated)
- First posted
- 28 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The COVID-19 pathology is frequently associated with diabetes mellitus and metabolic syndrome. In the epidemic outbreak that exploded at the beginning of 2020 in the Lombardy Region, about two thirds of the patients who died from COVID-19 were affected by diabetes mellitus. COVID-19 occurs in 70% of cases with an inflammatory pathology of the airways that can be fed by a cytokine storm and result in severe respiratory failure (10% cases) and death (5%). The pathophysiological molecular mechanisms are currently not clearly defined. It is hypothesized that the transmembrane glycoprotein type II CD26, known for the enzyme activity Dipeptilpeptidase 4 of the extracellular domain, may play a main role in this condition. It is in fact considerably expressed at the level of parenchyma and pulmonary interstitium and carries out both systemic and paracrine enzymatic activity, modulating the function of various proinflammatory cytokines, growth factors and vasoactive peptides in the deep respiratory tract. Of particular interest is the fact that Dipeptilpeptidase 4 has been identified as a cellular receptor for S glycoprotein of MERS-COV. In the case of the SARS-COV 2 virus, the main receptor is the Angiotensin-Converting Enzyme 2 protein, but a possible interaction with Dipeptilpeptidase 4 also cannot be excluded. The selective blockade of Dipeptilpeptidase 4 could therefore favorably modulate the pulmonary inflammatory response in the subject affected by COVID-19. This protein is also known for the enzymatic degradation function of the native glucagon-like peptide 1, one of the main regulators of insulin secretion. This is why it is a molecular target in the treatment of diabetes (drugs that selectively inhibit Dipeptilpeptidase 4 are marketed with an indication for the treatment of type 2 diabetes). It is believed that the use of a Dipeptilpeptidase 4 inhibitor in people with diabetes and hospitalized for Covid-19 may be safe and of particular interest for an evaluation of the effects on laboratory and instrumental indicators of inflammatory lung disease. Among the drugs that selectively block Dipeptilpeptidase 4, the one with the greatest affinity is Sitagliptin.
Detailed description
The investigators propose a randomized controlled open label intervention study. Patients hospitalized for COVID-19 and affected by type 2 diabetes mellitus will be included in the study and divided into two groups by randomization: sitagliptin add-on standard of care therapy with nutritional therapy with or without insulin treatment (study group) vs nutritional therapy with or without insulin treatment (group of control, standard therapy). The design of the study provides an open randomization to allow its feasibility in times compatible with the achievement of adequate cases during the epidemic. The presence of placebo and a double-blind study, would lead to longer planning and enrollment times.
Patients with type 2 diabetes mellitus hospitalized for COVID-19 and randomized to the study group will be treated with sitagliptin at an adjusted dosage for estimated glomerular filtrate: 100 mg once daily (estimated glomerular filtration rate less than or equal to 45 mL / min / 1.73 m2) or 50 mg (estimated glomerular filtration rate 30-45 mL / min / 1.73 m2) in combination or not with insulin treatment. Patients with stage IV and V renal impairment (estimated glomerular filtration rate less than or equal to 30 mL / min / 1.73 m2) will be excluded. Enrolled patients will be followed according to the following scheme:
Time points:
- T0: The doctor explains the protocol to the patient and he gives to him the informed consent and the letter to the general practitioner.
- T1: The patient gives the signed and dated consent and officially enters the study. Basic assessments will be made. At the baseline, the clinical response, the main laboratory and instrumental tests will be taken into consideration. Biological samples will be taken for immunological study. Diabetic patients will begin treatment with Sitagliptin 100 or 50 mg add-on to nutritional therapy and, eventually, insulin treatment. Any other hypoglycemic agents taken before admission will be suspended.
- T2: 7 days after T1, for both groups of patients, evaluation of the clinical response, of the average daily blood glucose levels, of the main laboratory and instrumental tests.
- T3: 10 days after T2, for both groups of patients, evaluation of clinical response, average daily blood glucose levels, of the main laboratory and instrumental tests. Collection of biological samples for immunological study. End of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A randomized controlled open label intervention study is proposed. Patients hospitalized for COVID-19 and suffering from type 2 diabetes will be included in the study and divided into two groups by randomization: sitagliptin add-on therapy with nutritional therapy with or without insulin (study group) vs nutritional therapy with or without insulin (group of control, standard therapy)
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Active comparator | Drug: Sitagliptinpatients will be treated with sitagliptin add on to nutritional therapy with o without insulin treatment. The dose of sitagliptin will be established on the basis of the estimated glomerular filtrate: 100 mg in single daily administration (estimated glomerular filtration rate less than or equal to 45 mL / min / 1.73 m2) or 50 mg (estimated glomerular filtration rate 30-45 mL / min / 1.73 m2) in combination or not with insulin. Patients with stage IV and V renal failure (estimated glomerular filtration rate less than or equal to 30 mL / min / 1.73 m2) will be excluded |
| Control group | No intervention | –Patients who will be prescribed nutritional therapy with or without insulin treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of type 2 diabetes, according to ADA 2020 criteria
- HbA1c levels at the entrance or in the two previous months <9%
- Diagnosis of Covid-19 (swab for positive SARS-COV2 RNA) with pneumonia, with or without increase in inflammation indexes, with or without respiratory failure
- No indication for tocilizumab therapy (BCRSS, Brescia Covid Respiratory Severity Scale, <3).
- Written and dated informed consent from the patient or his legally valid representative
Key exclusion criteria (15 listed)
- Pregnancy
- Type 1 diabetes
- Stage IV and V renal failure (stimated glomerular filtration rate <30 ml / min)
- Treatment with Dipeptidyl peptidase-4 inhibitors or GLP-1 Receptor Agonists in the month prior to hospitalization
- Pioglitazone treatment in the month prior to hospitalization
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SitagliptinWe propose a randomized controlled open label intervention study. Patients with type 2 diabetes admitted to COVID-19 and randomized to the study group will be treated with sitagliptin at an adjusted dosage for estimated glomerular filtrate: 100 mg once daily (estimated glomerular filtration rate less than or equal to 45 mL / min / 1.73 m2 ) or 50 mg (estimated glomerular filtration rate 30-45 mL / min / 1.73 m2) in combination or not with insulin. Patients with stage IV and V renal failure (estimated glomerular filtration rate less than or equal to 30 mL / min / 1.73 m2) will be excluded | Drug | Treatment group |
Primary outcome
Time for clinical improvement
Time frame: 1 month
Evaluation of the time between randomization and two-point improvement on a seven-category scale (1, not hospitalized, return to normal activities; 2, not hospitalized, but unable to return to normal activities; 3, hospitalized without the need for oxygen therapy; 4, hospitalized, need for oxygen therapy; 5, hospitalized, need for non-invasive ventilatory support; 6, hospitalized, need for invasive mechanical ventilation or Extra Corporeal Membrane Oxygenation; 7, death)
Clinical parameter of acute lung disease
Time frame: 1 month
Clinical evaluation of the physiological parameter "cough" associated with acute lung disease from the start of the study to the end of the study.
Biochemical parameter of acute lung disease
Time frame: 1 month
Variation of biochemical parameter "glycemia" of acute lung disease from the beginning of the study to the end of study.
Clinical parameter of acute lung disease
Time frame: 1 month
Variation of the clinical parameter "oxygen saturation by the use of a pulse oximeter" of acute lung disease from the beginning of the study to the end of the study.
Clinical parameter of acute lung disease
Time frame: 1 month
Variation of the clinical parameter "body temperature" of acute lung disease from the beginning of the study to the end of the study.
Clinical parameter of acute lung disease
Time frame: 1 month
Variation of the clinical parameter "respiratory rate" of acute lung disease from the beginning of the study to the end of the study.
Clinical parameter of acute lung disease
Time frame: 1 month
Variation of the clinical parameter "need for ventilatory support" of acute lung disease from the beginning of the study to the end of the study.
Clinical parameters of acute lung disease
Time frame: 1 month
Variation of the clinical parameters "duration in days of ventilatory support, duration in days of oxygen therapy, duration in days of hospitalization, duration in days in the Intensive Care Unit, total length of stay in hospital" of acute lung disease from the beginning of the study to the end of the study.
Clinical parameter of acute lung disease
Time frame: 1 month
Variation of the clinical parameter "blood gas analysis" of acute lung disease from the beginning of the study to the end of the study.
Clinical parameter of acute lung disease
Time frame: 1 month
Variation of the clinical parameter "chest X ray" of acute lung disease from the beginning of the study to the end of the study.
Clinical parameter of acute lung disease
Time frame: 1 month
Variation of the clinical parameter "PaO2/FiO2 ratio" of acute lung disease from the beginning of the study to the end of the study.
Biochemical parameter of acute lung disease
Time frame: 1 month
Variation of biochemical parameter "reactive C protein" of acute lung disease from the beginning of the study to the end of study.
Biochemical parameter of acute lung disease
Time frame: 1 month
Variation of biochemical parameter "blood count with formula" of acute lung disease from the beginning of the study to the end of study.
Biochemical parameter of acute lung disease
Time frame: 1 month
Variation of biochemical parameter "erythrocyte sedimentation rate" of acute lung disease from the beginning of the study to the end of study.
Biochemical parameter of acute lung disease
Time frame: 1 month
Variation of biochemical parameter "blood gas analysis" of acute lung disease from the beginning of the study to the end of study.
Biochemical parameter of acute lung disease
Time frame: 1 month
Variation of biochemical parameter "LDH" of acute lung disease from the beginning of the study to the end of study.
9 secondary outcomes
Dipeptilpeptidase 4 expression in biological samples
Time frame: 6 months
Cytokine-inflammatory profile
Time frame: 6 months
Glycemic variability
Time frame: 1 month
Glycemic variability
Time frame: 1 month
Cytokine-inflammatory profile
Time frame: 6 months
Cytokine-inflammatory profile
Time frame: 6 months
Cytokine-inflammatory profile
Time frame: 6 months
Cytokine-inflammatory profile
Time frame: 6 months
Cytokine-inflammatory profile
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2021.
- Background: PubMed 16759303Yang JK, Feng Y, Yuan MY, Yuan SY, Fu HJ, Wu BY, Sun GZ, Yang GR, Zhang XL, Wang L, Xu X, Xu XP, Chan JC. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006 Jun;23(6):623-8. doi: 10.1111/j.1464-5491.2006.01861.x.
- Background: PubMed 31279728Perlman S, Azhar EI, Memish ZA, Hui DS, Zumla A. Confronting the persisting threat of the Middle East respiratory syndrome to global health security. Lancet Infect Dis. 2020 Feb;20(2):158-160. doi: 10.1016/S1473-3099(19)30347-0. Epub 2019 Jul 3. No abstract available.
- Background: PubMed 32178769Remuzzi A, Remuzzi G. COVID-19 and Italy: what next? Lancet. 2020 Apr 11;395(10231):1225-1228. doi: 10.1016/S0140-6736(20)30627-9. Epub 2020 Mar 13.
- Background: PubMed 32105632Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
- Background: PubMed 31971463Zou H, Zhu N, Li S. The emerging role of dipeptidyl-peptidase-4 as a therapeutic target in lung disease. Expert Opin Ther Targets. 2020 Feb;24(2):147-153. doi: 10.1080/14728222.2020.1721468. Epub 2020 Jan 31.
- Background: PubMed 26597880Meyerholz DK, Lambertz AM, McCray PB Jr. Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract: Implications for the Middle East Respiratory Syndrome. Am J Pathol. 2016 Jan;186(1):78-86. doi: 10.1016/j.ajpath.2015.09.014. Epub 2015 Nov 18.
- Background: PubMed 23805228Ikeda T, Kumagai E, Iwata S, Yamakawa A. Soluble CD26/Dipeptidyl Peptidase IV Enhances the Transcription of IL-6 and TNF-alpha in THP-1 Cells and Monocytes. PLoS One. 2013 Jun 21;8(6):e66520. doi: 10.1371/journal.pone.0066520. Print 2013.
- Background: PubMed 23486063Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013 Mar 14;495(7440):251-4. doi: 10.1038/nature12005.
- Background: PubMed 32125455Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020 Apr;46(4):586-590. doi: 10.1007/s00134-020-05985-9. Epub 2020 Mar 3. No abstract available.
- Background: PubMed 32178593Vankadari N, Wilce JA. Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerg Microbes Infect. 2020 Mar 17;9(1):601-604. doi: 10.1080/22221751.2020.1739565. eCollection 2020.
- Background: PubMed 31550243Kulcsar KA, Coleman CM, Beck SE, Frieman MB. Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection. JCI Insight. 2019 Oct 17;4(20):e131774. doi: 10.1172/jci.insight.131774.
- Background: PubMed 28348219Li K, Wohlford-Lenane CL, Channappanavar R, Park JE, Earnest JT, Bair TB, Bates AM, Brogden KA, Flaherty HA, Gallagher T, Meyerholz DK, Perlman S, McCray PB Jr. Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice. Proc Natl Acad Sci U S A. 2017 Apr 11;114(15):E3119-E3128. doi: 10.1073/pnas.1619109114. Epub 2017 Mar 27.
- Individual participant dataSharing planned: No
Related trials for Covid19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paolo Fiorina, MD, PhD principal investigator
University of Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sitagliptin in people with Covid19 and Diabetes Mellitus, Type 2, run by University of Milan at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Teresa Letizia, Dr. (02 39042648, letizia.teresa@asst-fbf-sacco.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time for clinical improvement (time frame: 1 month). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04365517, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2021.