Role of TMEM219 Marker in Type 1 Diabetes

Diabetes Mellitus Clinical Trial

— NPOD  

Official title:

Ruolo Del Marcatore TMEM219 in Corso di Diabete di Tipo 1

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03794739
• Other study ID #: 2018/ST/080
• Status: Recruiting
• Start date: August 8, 2020
• Est. completion date: December 2023

Study information

• Verified date: May 2023
• Source: University of Milan
• Contact: Francesca D'Addio, MD,PhD
• Phone: +390250319820
• Email: francesca.daddio[@]unimi.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Type 1 diabetes (T1D) is a chronic metabolic disease characterized by autoimmune destruction of β cells of the insulin producing pancreatic islets. The different immunological approaches implemented to date to treat T1D have obtained a negligible number of insulin-independent individuals. The initial stages of diabetic disease are characterized by the massive and progressive infiltration of T cells and autoantibodies within the tissue with the consequent development of insulitis and subsequently, the destruction of pancreatic beta cells. The onset of T1D has been mainly associated to a dysregulation of the immune response. However, data are emerging on the importance of non-immunological factors responsible for the damage to pancreatic beta cells. The investigators have recently shown that the expression of the TMEM219 death factor is an essential factor in controlling the fate of stem cells in diabetes.

The aim of the study is to identify new markers in the mechanism of damage to pancreatic beta cells in the onset of type 1 diabetes, with particular reference to apoptotic factors such as TMEM219.

Description:

METHODS OF RECRUITING THE SUBJECTS Healthy subjects, individuals with type 1 and type 2 diabetes and those who are at risk of developing diabetes will be enrolled. Enrollment was approved by the University of Florida Ethics Committee within the NPOD project, Network for the Pancreatic Organ Donors with Diabetes.

Duration of the study: 5 years.

EXPERIMENTAL PROCEDURE:

The following analyses will be performed on the collected and received samples:

• Study of TMEM219 expression and of other TMEM219-related markers by immunohistochemistry and immunofluorescence and western blot

• Study of TMEM219 expression and of other TMEM219-related markers by molecular biology analysis

• Analysis of the proteomic profile on collected biological liquids The above analyses will be performed at the Pediatric Clinical Research Center Romeo ed Enrica Invernizzi at the Sacco Hospital - University of Milan.

PREVIOUS EXPERIENCES The investigatore expertise in manipulating / studying the signaling involved in the pathogenesis of type 1 diabetes has been widely recognized in several publications in recent years (Diabetes 2013, Diabetes 2014, Diabetes 2015, Science Translational Medicine 2017) as well as the characterization of marker expression including TMEM219 (Cell Stem Cell 2015).

RELEVANCE OF THE STUDY The study offers the possibility to acquire new information on the pathogenesis of diabetes and to identify new target mechanisms for designing innovative therapeutic strategies in the treatment of diabetes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Reported in the NPOD protocol

Exclusion Criteria:

• Reported in the NPOD protocol

Related Conditions & MeSH terms

• Diabetes Mellitus

Locations

Country	Name	City	State
Italy	Pediatric Clinical Research Center	Milan

Sponsors (1)

Lead Sponsor	Collaborator
University of Milan

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Altered TMEM219 expression in pancreatic islets/beta cells in diabetes.	Change of TMEM219 expression in pancreatic islets/beta cells of healthy subjects as compared to that of individuals with type 1 diabetes (T1D), with type 2 diabetes (T2D) and of those at risk for developing the disease.	1-24 months
Secondary	Increased beta cell loss due to a dysregulated TMEM219 signaling in diabetes.	Change in TMEM219-related factors and signaling in pancreatic islets/beta cells of healthy subjects as compared to individuals with T1D, with T2D and of individuals at risk for developing the disease.	25 months-48 months
Secondary	Altered TMEM219-peripheral regulating factors in diabetes.	Change of peripheral factors involved in controlling TMEM219 expression/activation detected in the serum of healthy subjects as compared to individuals with T1D, with T2D and at risk for developing the disease.	49 months-60 months