COVID19COBETOXNCT04463849
Effects of COVID-19 Infection on Beta-cell Function in Euglycemic Patients
A study testing Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection in people with COVID19 and BETA-CELL FUNCTION, run by University of Milan at 1 site in Italy.
Trial summary
In recent months, a new coronavirus, SARS-CoV-2, has been identified as the cause of a serious lung infection named COVID-19 by the World Health Organization. This virus has spread rapidly among the nations of the world and it is the cause of a pandemic and a global health emergency. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- COVID19, BETA-CELL FUNCTION
- What is being tested?
- Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteItaly
- Study dates
- 30 Jun 2020to 31 Dec 2021
- Phase
- Interventional
- 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 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and female patients with COVID19 and normal basal blood sugar, unprecedented in diabetes or impaired fasting glucose or impaired glucose tolerance
- Age> 18 years and <80 years
- Availability to informed consent and corporate privacy
- Male and female patients not affected by COVID19, unprecedented in diabetes or impaired fasting glucose or impaired glucose tolerance
- Age> 18 years and <80 years
- Availability to informed consent and corporate privacy
Show all 9Show fewer
- Male and female patients not affected by COVID19 with a diagnosis of type 2 diabetes
- Age> 18 years and <80 years
- Availability to informed consent and corporate privacy
Who cannot join
- Age <18 years
- Previous history of diabetes or impaired fasting glucose or impaired glucose tolerance
- Severe liver failure
- Severe kidney failure
- Age <18 years
- Previous history of diabetes or impaired fasting glucose or impaired glucose tolerance
Show all 13Show fewer
- Positivity to the nasopharyngeal swab for SARS-CoV-2
- Severe liver failure
- Severe kidney failure
- Age <18 years
- Positivity to the nasopharyngeal swab for SARS-CoV-2
- Severe liver failure
- Severe kidney failure
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of SARS-CoV-2 Infection on Beta-cell Function in Euglycemic Patients
In recent months, a new coronavirus, SARS-CoV-2, has been identified as the cause of a serious lung infection named COVID-19 by the World Health Organization. This virus has spread rapidly among the nations of the world and it is the cause of a pandemic and a global health emergency. There is still very little scientific evidence on the virus, however epidemiological data suggest that one of the most frequent comorbidities is diabetes, along with hypertension and heart disease. There is no scientific evidence on the possible effects of this infection on the function of the β cell and on glycemic control. Clinical evidence seems to suggest that COVID-19 infection mostly affects the respiratory system, and an acute worsening of glycemic compensation is not described as generally observed in bacterial pneumonia. However, previous work on acute respiratory syndromes (SARS) caused by similar coronaviruses, had described that the infection has multi-organ involvement related to the expression of the SARS coronavirus receptor, the angiotensin 2 converting enzyme, in different organs, especially at the level of endocrine pancreatic tissue. In the population of this previous work, glucose intolerance and fasting hyperglycaemia have been described and in 37 of 39 diabetic patients examined, a remission of diabetes was observed three years after the infection. It is possible that the coronaviruses responsible for SARS may enter the pancreatic islets using the angiotensin 2 converting enzyme receptor, expressed at the level of the endocrine pancreas, thus causing diabetes. Additionally, previous literature on coronavirus infections (SARS and MERS or Middle-East Respiratory Syndrome) suggested that diabetes could worsen the evolution of the disease. In particular, in case of Middle-East Respiratory Syndrome-CoV infection, diabetic mice had a more prolonged serious illness and a delay in recovery regardless of the viremic titer. This could probably be due to a dysregulation of the immune response, which results in more serious and prolonged lung disease.
There are currently no data on pancreatic beta cell function in patients with COVID-19.
Read the detailed description
The project is monocentric, interventional, non-pharmacological, non-profit. Patients will be enrolled in hospital for confirmed COVID-19 infection (with reverse transcriptase-polymerase chain reaction on the airway swab) but with normal basal blood glucose and no previous history of diabetes or impaired fasting glucose or impaired glucose tolerance. Patients will be compared to a control group of healthy volunteers, not affected by COVID-19 and with no previous history of diabetes or impaired fasting glucose or impaired glucose tolerance. Patients will be also compared with a group of patients with type 2 diabetes but without COVID-19. Once the informed consent has been signed, the clinical parameters and biochemical parameters will be collected according to the time points provided by the protocol in positive COVID-19 patients, in healthy volunteers and in patients with type 2 diabetes.
COVID-19 positive patients and healthy controls as well as patients with type 2 diabetes, will undergo a stimulation test of β-cell function (evaluation of the secretive response of insulin to the stimulation test with arginine infusion) and the monitoring of glycemic values through a professional retrospective continuous glucose monitoring. For the test, an infusion solution containing 25% arginine hydrochloride will be used, arginine is an insulinogenic amino acid, useful to verify the possible existence of damage to the cellular beta function induced by COVID-19 infection, clinically observable with changes in insulin secretory response. Given the usefulness of the test, performed for diagnostic purposes, this protocol is identified as "non-pharmacological". The test is contraindicated only in patients with severe hepatic and renal insufficiency, in all other subjects the side effects are minimal and spontaneous resolution before the end of the test (flushing 33%, oral paraesthesia 46%, nausea 12%, dizziness 14%). For the stimulation test with arginine infusion, after the basal sampling at (0 minutes), an intravenous injection of arginine 5 grams will be practiced in 60 seconds followed by serial withdrawals at +2, +5, +10 and +30 minutes. The following analytes will be assayed on the basal sample: glycosylated hemoglobin, glycaemia, insulin, pro-insulin, C-peptide, glucagon, serum inflammatory cytokines (Il1β, IL-2, IL-6, IL-7, IL-10, TNF- α, IFN-γ, MIP-1β, MCP-1, GM-CSF, G-CSF Insulin, C-peptide and glucagon will be dosed on all points of the curve.
- Conditions
- COVID19, BETA-CELL FUNCTION
- Being tested
- Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infectionDiagnostic test
Also called Positioning of the device for glycemic monitoring
All participants will be subjected to the collection of glycemic data through continuous professional retrospective monitoring of blood glucose for seven days, positioned on the day the test will be performed. During the entire recording period, parameters such as mean glucose, estimated glycosylated hemoglobin, peak glucose and nadir, blood sugar levels above the limit of 140 mg / dL, average glucose values at 60 and 120 minutes after meals, standard deviation and variability coefficient.
The evaluation of insulin secretion will be evaluated by performing the stimulus test with arginine infusion according to validated protocols.
| Study group | Role | What they receive |
|---|---|---|
| COVID-19 positive patients | Experimental | Patients will be enrolled in hospital for confirmed COVID-19 infection (with reverse transcriptase-polymerase chain reaction on the airway swab) but with normal basal glucose and no previous history of diabetes or impaired fasting glucose or impaired tolerance glucose. Patients will be placed with a professional retrospective glucose monitoring device and will be tested for stimulation with arginine infusion. The device will be placed on the day of the test and will be removed after seven days of recording the glycemic data. During the entire recording period, parameters such as mean glucose, estimated glycosylated hemoglobin, peak glucose and nadir, blood sugar levels above the limit of 140 mg / dL, average glucose values at 60 and 120 minutes after meals, standard deviation and variability coefficient. Receives: Diagnostic Test: Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection |
| Healthy volunteers | Other | Healthy volunteers, not affected by COVID-19 and with no previous history of diabetes or impaired fasting glucose or impaired glucose tolerance will be enrolled. Healthy volunteers will be placed with a professional retrospective glucose monitoring device and will be tested for stimulation with arginine infusion. The device will be placed on the day of the test and will be removed after seven days of recording the glycemic data. During the entire recording period, parameters such as mean glucose, estimated glycosylated hemoglobin, peak glucose and nadir, blood sugar levels above the limit of 140 mg / dL, average glucose values at 60 and 120 minutes after meals, standard deviation and variability coefficient. Receives: Diagnostic Test: Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection |
| Type 2 diabetes patients | Other | Patients with established Type 2 diabetes, not affects by COVID-19. Patients will be placed with a professional retrospective glucose monitoring device and will be tested for stimulation with arginine infusion. The device will be placed on the day of the test and will be removed after seven days of recording the glycemic data. During the entire recording period, parameters such as mean glucose, estimated glycosylated hemoglobin, peak glucose and nadir, blood sugar levels above the limit of 140 mg / dL, average glucose values at 60 and 120 minutes after meals, standard deviation and variability coefficient. Receives: Diagnostic Test: Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum β - cellular function index insulin levels
Difference in insulin levels during and after COVID-19 infection and compared to patients in the control group
Measured: all data were collected at Visit 1, 12 months
Serum β - cellular function index C-peptide levels
Difference in C-peptide levels during and after COVID-19 infection and compared to patients in the control group
Measured: all data were collected at Visit 1, 12 months
Serum β - cellular function HOMA-β index
Difference in HOMA-β index during and after COVID-19 infection and compared to patients in the control group
Measured: all data were collected at Visit 1, 12 months
Serum β - cellular function pro-insulin/insulin ratio
Difference in pro-insulin/insulin ratio during and after COVID-19 infection and compared to patients in the control group
Measured: all data were collected at Visit 1, 12 months
Evaluation of the secretory response of insulin to the arginine stimulation test
Check for the existence of damage to the beta cell function induced by COVID-19 infection, clinically observable with changes in the secretory response of insulin
Measured: all data were collected at Visit 1, 12 months
Percentage of patients with preserved β cells function
Evidence of impairment of β cell function in the serum of COVID-19 patients
Measured: all data were collected at Visit 1, 12 months
Secondary outcomes (13)
Glucose values
Changes in glucose values in COVID-19 patients and healthy volunteers
Measured: all data were collected at Visit 1, 12 months
Values of continuous glucose monitoring
Changes in the values of continuous glucose monitoring in both COVID-19 patients and healthy volunteers
Measured: all data were collected at Visit 1 and after 7 days, 12 months
Changes in the inflammatory marker interleukin 1-β
Comparison of interleukin 1-β levels in COVID-19 patients compared with healthy subjects
Measured: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker interleukin IL-2
Comparison of interleukin IL-2 levels in COVID-19 patients compared with healthy subjects
Measured: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker interleukin IL-6
Comparison of interleukin IL-6 levels in COVID-19 patients compared with healthy subjects
Measured: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker interleukin IL-7
Comparison of interleukin IL-7 levels in COVID-19 patients compared with healthy subjects
Measured: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker interleukin IL-10
Comparison of interleukin IL-10 levels in COVID-19 patients compared with healthy subjects
Measured: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker tumor necrosis factor-α
Comparison of interleukin tumor necrosis factor-α levels in COVID-19 patients compared with healthy subjects
Measured: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker interferon gamma
Comparison of interferon gamma levels in COVID-19 patients compared with healthy subjects
Measured: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker macrophage inflammatory protein-1β
Comparison of macrophage inflammatory protein-1β levels in COVID-19 patients compared with healthy subjects
Measured: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker monocyte chemoattractant protein-1
Comparison of macrophage inflammatory monocyte chemoattractant protein-1 in COVID-19 patients compared with healthy subjects
Measured: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker granulocyte-macrophage colony-stimulating factor
Comparison of macrophage inflammatory granulocyte-macrophage colony-stimulating factor in COVID-19 patients compared with healthy subjects
Measured: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker granulocyte colony-stimulating factor
Comparison of macrophage inflammatory granulocyte colony-stimulating factor in COVID-19 patients compared with healthy subjects
Measured: all data were collected at Visit 1, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2020
- Study start30 Jun 2020
- Primary completion31 Oct 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Collaborators
- Luigi Sacco University Hospital
- Responsible party
- Principal investigator, Paolo Fiorina, MD, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04463849
- Sponsor's protocol ID
- 6/2020
- Acronym
- COBETOX
- Status last verified
- May 2023
- First submitted
- 2 Jul 2020
- Last updated
- 10 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Deng SQ, Peng HJ. Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China. J Clin Med. 2020 Feb 20;9(2):575. doi: 10.3390/jcm9020575.
PubMed 32093211Kulcsar 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 31550243Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
PubMed 31986264Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010 Sep;47(3):193-9. doi: 10.1007/s00592-009-0109-4. Epub 2009 Mar 31.
PubMed 19333547Shankar SS, Vella A, Raymond RH, Staten MA, Calle RA, Bergman RN, Cao C, Chen D, Cobelli C, Dalla Man C, Deeg M, Dong JQ, Lee DS, Polidori D, Robertson RP, Ruetten H, Stefanovski D, Vassileva MT, Weir GC, Fryburg DA; Foundation for the National Institutes of Health beta-Cell Project Team. Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of beta-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series. Diabetes Care. 2016 Sep;39(9):1602-13. doi: 10.2337/dc15-0931. Epub 2016 Jul 12.
PubMed 27407117Brandle M, Lehmann R, Maly FE, Schmid C, Spinas GA. Diminished insulin secretory response to glucose but normal insulin and glucagon secretory responses to arginine in a family with maternally inherited diabetes and deafness caused by mitochondrial tRNA(LEU(UUR)) gene mutation. Diabetes Care. 2001 Jul;24(7):1253-8. doi: 10.2337/diacare.24.7.1253.
PubMed 11423511Bolla AM, Loretelli C, Montefusco L, Finzi G, Abdi R, Ben Nasr M, Lunati ME, Pastore I, Bonventre JV, Nebuloni M, Rusconi S, Santus P, Zuccotti G, Galli M, D'Addio F, Fiorina P. Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID-19. Diabetes Metab Res Rev. 2022 Oct;38(7):e3565. doi: 10.1002/dmrr.3565. Epub 2022 Jul 22.
PubMed 35830597Ben Nasr M, D'Addio F, Montefusco L, Usuelli V, Loretelli C, Rossi A, Pastore I, Abdelsalam A, Maestroni A, Dell'Acqua M, Ippolito E, Assi E, Seelam AJ, Fiorina RM, Chebat E, Morpurgo P, Lunati ME, Bolla AM, Abdi R, Bonventre JV, Rusconi S, Riva A, Corradi D, Santus P, Clark P, Nebuloni M, Baldi G, Finzi G, Folli F, Zuccotti GV, Galli M, Herold KC, Fiorina P. Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets. Diabetes. 2022 Jul 1;71(7):1579-1590. doi: 10.2337/db21-0926.
PubMed 35499468
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of SARS-CoV-2 Infection on Beta-cell Function in Euglycemic Patients
- ClinicalTrials.gov ID
- NCT04463849
- Acronym / sponsor ID
- COBETOX / 6/2020
- Conditions
- COVID19, BETA-CELL FUNCTION
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Collaborators
- Luigi Sacco University Hospital
- Study start
- 30 Jun 2020 (actual)
- Primary completion
- 31 Oct 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 9 Jul 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.
In recent months, a new coronavirus, SARS-CoV-2, has been identified as the cause of a serious lung infection named COVID-19 by the World Health Organization. This virus has spread rapidly among the nations of the world and it is the cause of a pandemic and a global health emergency. There is still very little scientific evidence on the virus, however epidemiological data suggest that one of the most frequent comorbidities is diabetes, along with hypertension and heart disease. There is no scientific evidence on the possible effects of this infection on the function of the β cell and on glycemic control. Clinical evidence seems to suggest that COVID-19 infection mostly affects the respiratory system, and an acute worsening of glycemic compensation is not described as generally observed in bacterial pneumonia. However, previous work on acute respiratory syndromes (SARS) caused by similar coronaviruses, had described that the infection has multi-organ involvement related to the expression of the SARS coronavirus receptor, the angiotensin 2 converting enzyme, in different organs, especially at the level of endocrine pancreatic tissue. In the population of this previous work, glucose intolerance and fasting hyperglycaemia have been described and in 37 of 39 diabetic patients examined, a remission of diabetes was observed three years after the infection. It is possible that the coronaviruses responsible for SARS may enter the pancreatic islets using the angiotensin 2 converting enzyme receptor, expressed at the level of the endocrine pancreas, thus causing diabetes. Additionally, previous literature on coronavirus infections (SARS and MERS or Middle-East Respiratory Syndrome) suggested that diabetes could worsen the evolution of the disease. In particular, in case of Middle-East Respiratory Syndrome-CoV infection, diabetic mice had a more prolonged serious illness and a delay in recovery regardless of the viremic titer. This could probably be due to a dysregulation of the immune response, which results in more serious and prolonged lung disease.
There are currently no data on pancreatic beta cell function in patients with COVID-19.
Detailed description
The project is monocentric, interventional, non-pharmacological, non-profit. Patients will be enrolled in hospital for confirmed COVID-19 infection (with reverse transcriptase-polymerase chain reaction on the airway swab) but with normal basal blood glucose and no previous history of diabetes or impaired fasting glucose or impaired glucose tolerance. Patients will be compared to a control group of healthy volunteers, not affected by COVID-19 and with no previous history of diabetes or impaired fasting glucose or impaired glucose tolerance. Patients will be also compared with a group of patients with type 2 diabetes but without COVID-19. Once the informed consent has been signed, the clinical parameters and biochemical parameters will be collected according to the time points provided by the protocol in positive COVID-19 patients, in healthy volunteers and in patients with type 2 diabetes.
COVID-19 positive patients and healthy controls as well as patients with type 2 diabetes, will undergo a stimulation test of β-cell function (evaluation of the secretive response of insulin to the stimulation test with arginine infusion) and the monitoring of glycemic values through a professional retrospective continuous glucose monitoring. For the test, an infusion solution containing 25% arginine hydrochloride will be used, arginine is an insulinogenic amino acid, useful to verify the possible existence of damage to the cellular beta function induced by COVID-19 infection, clinically observable with changes in insulin secretory response. Given the usefulness of the test, performed for diagnostic purposes, this protocol is identified as "non-pharmacological". The test is contraindicated only in patients with severe hepatic and renal insufficiency, in all other subjects the side effects are minimal and spontaneous resolution before the end of the test (flushing 33%, oral paraesthesia 46%, nausea 12%, dizziness 14%). For the stimulation test with arginine infusion, after the basal sampling at (0 minutes), an intravenous injection of arginine 5 grams will be practiced in 60 seconds followed by serial withdrawals at +2, +5, +10 and +30 minutes. The following analytes will be assayed on the basal sample: glycosylated hemoglobin, glycaemia, insulin, pro-insulin, C-peptide, glucagon, serum inflammatory cytokines (Il1β, IL-2, IL-6, IL-7, IL-10, TNF- α, IFN-γ, MIP-1β, MCP-1, GM-CSF, G-CSF Insulin, C-peptide and glucagon will be dosed on all points of the curve.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| COVID-19 positive patients | Experimental | Diagnostic Test: Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infectionPatients will be enrolled in hospital for confirmed COVID-19 infection (with reverse transcriptase-polymerase chain reaction on the airway swab) but with normal basal glucose and no previous history of diabetes or impaired fasting glucose or impaired tolerance glucose. Patients will be placed with a professional retrospective glucose monitoring device and will be tested for stimulation with arginine infusion. The device will be placed on the day of the test and will be removed after seven days of recording the glycemic data. During the entire recording period, parameters such as mean glucose, estimated glycosylated hemoglobin, peak glucose and nadir, blood sugar levels above the limit of 140 mg / dL, average glucose values at 60 and 120 minutes after meals, standard deviation and variability coefficient. |
| Healthy volunteers | Other | Diagnostic Test: Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infectionHealthy volunteers, not affected by COVID-19 and with no previous history of diabetes or impaired fasting glucose or impaired glucose tolerance will be enrolled. Healthy volunteers will be placed with a professional retrospective glucose monitoring device and will be tested for stimulation with arginine infusion. The device will be placed on the day of the test and will be removed after seven days of recording the glycemic data. During the entire recording period, parameters such as mean glucose, estimated glycosylated hemoglobin, peak glucose and nadir, blood sugar levels above the limit of 140 mg / dL, average glucose values at 60 and 120 minutes after meals, standard deviation and variability coefficient. |
| Type 2 diabetes patients | Other | Diagnostic Test: Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infectionPatients with established Type 2 diabetes, not affects by COVID-19. Patients will be placed with a professional retrospective glucose monitoring device and will be tested for stimulation with arginine infusion. The device will be placed on the day of the test and will be removed after seven days of recording the glycemic data. During the entire recording period, parameters such as mean glucose, estimated glycosylated hemoglobin, peak glucose and nadir, blood sugar levels above the limit of 140 mg / dL, average glucose values at 60 and 120 minutes after meals, standard deviation and variability coefficient. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female patients with COVID19 and normal basal blood sugar, unprecedented in diabetes or impaired fasting glucose or impaired glucose tolerance
- Age> 18 years and <80 years
- Availability to informed consent and corporate privacy
- Male and female patients not affected by COVID19, unprecedented in diabetes or impaired fasting glucose or impaired glucose tolerance
- Age> 18 years and <80 years
Key exclusion criteria (13 listed)
- Age <18 years
- Previous history of diabetes or impaired fasting glucose or impaired glucose tolerance
- Severe liver failure
- Severe kidney failure
- Age <18 years
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 |
|---|---|---|
| Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infectionAlso: Positioning of the device for glycemic monitoringAll participants will be subjected to the collection of glycemic data through continuous professional retrospective monitoring of blood glucose for seven days, positioned on the day the test will be performed. During the entire recording period, parameters such as mean glucose, estimated glycosylated hemoglobin, peak glucose and nadir, blood sugar levels above the limit of 140 mg / dL, average glucose values at 60 and 120 minutes after meals, standard deviation and variability coefficient. The evaluation of insulin secretion will be evaluated by performing the stimulus test with arginine infusion according to validated protocols. | Diagnostic test | COVID-19 positive patients, Healthy volunteers, Type 2 diabetes patients |
Primary outcome
Serum β - cellular function index insulin levels
Time frame: all data were collected at Visit 1, 12 months
Difference in insulin levels during and after COVID-19 infection and compared to patients in the control group
Serum β - cellular function index C-peptide levels
Time frame: all data were collected at Visit 1, 12 months
Difference in C-peptide levels during and after COVID-19 infection and compared to patients in the control group
Serum β - cellular function HOMA-β index
Time frame: all data were collected at Visit 1, 12 months
Difference in HOMA-β index during and after COVID-19 infection and compared to patients in the control group
Serum β - cellular function pro-insulin/insulin ratio
Time frame: all data were collected at Visit 1, 12 months
Difference in pro-insulin/insulin ratio during and after COVID-19 infection and compared to patients in the control group
Evaluation of the secretory response of insulin to the arginine stimulation test
Time frame: all data were collected at Visit 1, 12 months
Check for the existence of damage to the beta cell function induced by COVID-19 infection, clinically observable with changes in the secretory response of insulin
Percentage of patients with preserved β cells function
Time frame: all data were collected at Visit 1, 12 months
Evidence of impairment of β cell function in the serum of COVID-19 patients
13 secondary outcomes
Glucose values
Time frame: all data were collected at Visit 1, 12 months
Values of continuous glucose monitoring
Time frame: all data were collected at Visit 1 and after 7 days, 12 months
Changes in the inflammatory marker interleukin 1-β
Time frame: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker interleukin IL-2
Time frame: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker interleukin IL-6
Time frame: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker interleukin IL-7
Time frame: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker interleukin IL-10
Time frame: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker tumor necrosis factor-α
Time frame: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker interferon gamma
Time frame: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker macrophage inflammatory protein-1β
Time frame: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker monocyte chemoattractant protein-1
Time frame: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker granulocyte-macrophage colony-stimulating factor
Time frame: all data were collected at Visit 1, 12 months
Changes in the inflammatory marker granulocyte colony-stimulating factor
Time frame: all data were collected at Visit 1, 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Background: PubMed 32093211Deng SQ, Peng HJ. Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China. J Clin Med. 2020 Feb 20;9(2):575. doi: 10.3390/jcm9020575.
- 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 31986264Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
- Background: PubMed 19333547Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010 Sep;47(3):193-9. doi: 10.1007/s00592-009-0109-4. Epub 2009 Mar 31.
- Background: PubMed 27407117Shankar SS, Vella A, Raymond RH, Staten MA, Calle RA, Bergman RN, Cao C, Chen D, Cobelli C, Dalla Man C, Deeg M, Dong JQ, Lee DS, Polidori D, Robertson RP, Ruetten H, Stefanovski D, Vassileva MT, Weir GC, Fryburg DA; Foundation for the National Institutes of Health beta-Cell Project Team. Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of beta-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series. Diabetes Care. 2016 Sep;39(9):1602-13. doi: 10.2337/dc15-0931. Epub 2016 Jul 12.
- Background: PubMed 11423511Brandle M, Lehmann R, Maly FE, Schmid C, Spinas GA. Diminished insulin secretory response to glucose but normal insulin and glucagon secretory responses to arginine in a family with maternally inherited diabetes and deafness caused by mitochondrial tRNA(LEU(UUR)) gene mutation. Diabetes Care. 2001 Jul;24(7):1253-8. doi: 10.2337/diacare.24.7.1253.
- Derived from this study: PubMed 35830597Bolla AM, Loretelli C, Montefusco L, Finzi G, Abdi R, Ben Nasr M, Lunati ME, Pastore I, Bonventre JV, Nebuloni M, Rusconi S, Santus P, Zuccotti G, Galli M, D'Addio F, Fiorina P. Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID-19. Diabetes Metab Res Rev. 2022 Oct;38(7):e3565. doi: 10.1002/dmrr.3565. Epub 2022 Jul 22.
- Derived from this study: PubMed 35499468Ben Nasr M, D'Addio F, Montefusco L, Usuelli V, Loretelli C, Rossi A, Pastore I, Abdelsalam A, Maestroni A, Dell'Acqua M, Ippolito E, Assi E, Seelam AJ, Fiorina RM, Chebat E, Morpurgo P, Lunati ME, Bolla AM, Abdi R, Bonventre JV, Rusconi S, Riva A, Corradi D, Santus P, Clark P, Nebuloni M, Baldi G, Finzi G, Folli F, Zuccotti GV, Galli M, Herold KC, Fiorina P. Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets. Diabetes. 2022 Jul 1;71(7):1579-1590. doi: 10.2337/db21-0926.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection in people with COVID19 and BETA-CELL FUNCTION, 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 9 inclusion and 13 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: finished, as of the sponsor's last update on 10 May 2023. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum β - cellular function index insulin levels (time frame: all data were collected at Visit 1, 12 months). The study lists 6 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 NCT04463849, which also lists 8 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 10 May 2023.