Covid-19 Infection and New Onset Type 1 Diabetes

Covid19 Clinical Trial

Official title:

Covid-19 and Type 1 Diabetes - a Multicenter Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04623697
• Other study ID #: S-20200119
• Status: Recruiting
• Start date: November 1, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2023
• Source: Hospital of South West Jutland
• Contact: Claus B Juhl, MD PhD
• Phone: +4560867172
• Email: Claus.Bogh.Juhl[@]rsyd.dk
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Although recognized as an autoimmune disease the etiology of type 1 diabetes remains unknown. Virus infections has been suggested as a possible agent triggering the autoimmune reaction finally resulting in beta-cell destruction and fate of insulin secretion. SARS Cov-2 virus enters the infected cells by binding to the ACE-2 receptor, which is abundant in many tissues including the pancreas. Accordingly, SARS Covid-19 infection may trigger the development of type 1 diabetes either by an activation of the immune system or directly via beta-cell infection and destruction.

Our aim is to study the impact of the Covid-19 epidemic on the development of type 1 diabetes. This will be done in two ways: a clinical study and an epidemiological follow up. During the next two years, adult patients with newly diagnosed type 1 diabetes will be asked to participate. Type 1 diabetes will be diagnosed by usual means and a mixed meal tolerance test will be performed at time of diagnosis and after one year to evaluate beta-cell function. People with type 1 diabetes and serologically documented previous SARS Covid-19 will be compared with people with no previous infection regarding beta-cell function and fate of insulin secretion. In addition, we will estimate the number of new diagnosed type 1 diabetes patients compared to previous years.

Description:

Background

Although recognized as an autoimmune disease, the etiology of type 1 diabetes mellitus (T1D) remains undetermined. One dominant hypothesis is that a recent virus infection elicits or enhances an autoimmune reaction, resulting in CD4+ and CD8+ T-cells recognizing pancreatic antigens and subsequently targeting the beta-cells of the pancreas. This results in a gradual but irreversible loss of beta-cell function.

Various enterovirus species have been suspected as causative factors of T1D. However, many different viruses may carry the potential to induce T1D via one of the above-mentioned mechanisms, including respiratory infections.

Most people are presently immunologically inert to SARS-Cov-2, but a large proportion of the world's population is expected to be infected over the next few years, with the global focus having now shifted to slowing the spread (1). The pandemic of COVID-19 therefore provides an opportunity to study a possible correlation between a novel type of virus infection and the development of T1D.

Aim

Our overall aim is to study the impact of Covid-19 on the incidence and the phenotype (beta-cell function at time of diagnosis and at follow up) of newly diagnosed adult patients with T1D in a multicenter study, with enrolments to occur in both Denmark and Portugal.

Method

The following study populations are established over a two-year period, beginning in October 2020:

1. Study population 1: Newly diagnosed adult patients with T1D according to usual practice, stratified for the presence of SARS-Cov-2-antibodies (+/-), in both Denmark and Portugal.

2. Study population 2: A control population of the same age (+/- 3 years) and sex from each participant country, potentially from the national blood banks. This will provide the SARS-Cov-2 status of the background population. Each newly diagnosed T1D patient is matched with five control persons.

Study 1: Clinical study: Study 1:

Inclusion criteria:

• T1D patients diagnosed according to standard practice (including Hba1c, C-peptide, presence of GAD (or islet-cell) antibodies).

• Patient is attending a hospital unit in Denmark or Portugal, due to T1D.

• Age 18 years or above.

Exclusion criteria:

• Severe psychiatric disorder or other conditions deemed to impair the patient's informed consent and participation in the study.

In each country, all subjects from study population 1 will undergo the following assessments at diagnosis of T1D:

1. SARS-Cov-2 antibody measurement.

2. GAD-antibodies (and if necessary islet cell antibodies (IA-2)).

3. HbA1c, fasting blood glucose and fasting C-peptide.

4. Mixed-meal tolerance test (MMTT).

5. Follow-up one year after the diagnosis with HbA1c, fasting blood glucose, fasting C-peptide and MMTT.

Study 2: Epidemiological study 1: In each country, the incidence of SARS-Covid-2 antibodies in study group 1 is compared to the matched control group (Study population 2).

Study 3: Epidemiological study 2: Independently of the above mentioned study, the incidence of newly diagnosed T1D patients in each participant country will be determined by registry data from January 1st 2020 on a monthly basis and compared with newly diagnosed T1D patients from the two previous years (2018 and 2019).

Outcomes

The study will have the following outcomes

Study 1 (clinical study):

Primary outcome: C-peptide AUC of the MMTT at baseline and one year follow-up, for adult T1D patients having SARS-Cov-2 positive vs. negative antibody status.

Secondary outcomes: Fasting glucose, C-peptide, Hba1c at baseline and one year follow-up, for adult T1D patients having SARS-Cov-2 positive vs. negative antibody status.

Study 2 (epidemiological study 1):

Outcome: Proportion of T1D patients having SARS-Cov-2 antibodies, compared to matched controls from the background population, potentially from the national blood banks (1:5 match on age, gender and if possible country region).

Study 3 (epidemiological study 2):

Outcome: Annual and monthly T1D incidence (cases/100.000) during 2020-2022, compared to 2018 and 2019 in Denmark and Portugal.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• T1D patients diagnosed according to standard practice (including Hba1c, C-peptide, presence of GAD (or islet-cell) antibodies).

• Patient is attending a hospital unit in Denmark or Portugal, due to T1D.

• Age 18 years or above.

Exclusion Criteria:

• Severe psychiatric disorder or other conditions deemed to impair the patient's informed consent and participation in the study.

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• type1diabetes

Locations

Country	Name	City	State
Denmark	Hospital of South West Jutland	Esbjerg

Sponsors (6)

Lead Sponsor	Collaborator
Hospital of South West Jutland	Aarhus University Hospital, Steno Diabetes Center Copenhagen, Steno Diabetes Center Nordjylland, Steno Diabetes Center Odense, Steno Diabetes Center Sjaelland

Country where clinical trial is conducted

Denmark, 

References & Publications (10)

Bindom SM, Lazartigues E. The sweeter side of ACE2: physiological evidence for a role in diabetes. Mol Cell Endocrinol. 2009 Apr 29;302(2):193-202. doi: 10.1016/j.mce.2008.09.020. Epub 2008 Oct 1. — View Citation

Christoffersson G, Flodstrom-Tullberg M. Mouse Models of Virus-Induced Type 1 Diabetes. Methods Mol Biol. 2020;2128:93-105. doi: 10.1007/978-1-0716-0385-7_7. — View Citation

Coleman TJ, Gamble DR, Taylor KW. Diabetes in mice after Coxsackie B 4 virus infection. Br Med J. 1973 Jul 7;3(5870):25-7. doi: 10.1136/bmj.3.5870.25. — View Citation

Filippi CM, von Herrath MG. Viral trigger for type 1 diabetes: pros and cons. Diabetes. 2008 Nov;57(11):2863-71. doi: 10.2337/db07-1023. No abstract available. — View Citation

Hyoty H, Leon F, Knip M. Developing a vaccine for type 1 diabetes by targeting coxsackievirus B. Expert Rev Vaccines. 2018 Dec;17(12):1071-1083. doi: 10.1080/14760584.2018.1548281. Epub 2018 Nov 29. — View Citation

Karaoglan M, Eksi F. The Coincidence of Newly Diagnosed Type 1 Diabetes Mellitus with IgM Antibody Positivity to Enteroviruses and Respiratory Tract Viruses. J Diabetes Res. 2018 Aug 16;2018:8475341. doi: 10.1155/2018/8475341. eCollection 2018. — View Citation

Moltchanova EV, Schreier N, Lammi N, Karvonen M. Seasonal variation of diagnosis of Type 1 diabetes mellitus in children worldwide. Diabet Med. 2009 Jul;26(7):673-8. doi: 10.1111/j.1464-5491.2009.02743.x. — View Citation

Patterson CC, Gyurus E, Rosenbauer J, Cinek O, Neu A, Schober E, Parslow RC, Joner G, Svensson J, Castell C, Bingley PJ, Schoenle E, Jarosz-Chobot P, Urbonaite B, Rothe U, Krzisnik C, Ionescu-Tirgoviste C, Weets I, Kocova M, Stipancic G, Samardzic M, de B — View Citation

Stone VM, Hankaniemi MM, Svedin E, Sioofy-Khojine A, Oikarinen S, Hyoty H, Laitinen OH, Hytonen VP, Flodstrom-Tullberg M. A Coxsackievirus B vaccine protects against virus-induced diabetes in an experimental mouse model of type 1 diabetes. Diabetologia. 2 — View Citation

Yang 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stimulated insulin secretion	C-peptide AUC of the MMTT at baseline and one year follow-up	One years
Secondary	HbA1c	HbA1c measure at one year	One years
Secondary	Fasting blood glucose	Fasting blood glucose	One years