Urine Extracellular Vesicles: Non-invasive Biomarkers of Β-cell Function and Novel Therapeutic Agents in Diabetes (EvsBioDiabetes)

Diabetes mellitus is a common chronic disease with a huge socioeconomic burden worldwide. Type 1 Diabetes(T1D) accounts for nearly 95% of diabetes in pediatric age and a lifelong dependence on exogenous insulin. Its diagnosis is based on symptoms and/or autoantibodies, both identified too late to avoid the disease progress. Ideally, children should be screened whilst assymptomatic, when there is endogenous insulin production, but C-peptide and beta-cell function are starting to decline. Early diagnosis would allow interventions capable of preventing disease progress and/or to preserve beta-cell function, ultimately delaying/avoiding insulin dependence. Given their association with pathogenesis of diabetes, Extracellular Vesicles have emerged as potential biomarkers for diagnosis and progression of diabetes. This project proposes the development of a non-invasive biomarker of preclinical T1D, based on miRNA characterization in urine, allowing a timely identification of children that can benefit from preventive therapies and, in the future, to cure T1D.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes Mellitus; Diabetes Mellitus, Type 1
• Intervention / Treatment: Diagnostic test: Blood and urine samples collection

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• Portugal
  • Coimbra, Portugal, 3000-602
    • Coimbra Pediatric Hospital - CHUC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Children and adolescents under follow-up at Coimbra Pediatric Hospital - Coimbra University and Hospital Centre (CHUC), either in specific clinic (Diabetes - for T1D group) or that have been observed at a general endocrine or pediatrics clinics for a suspition of disease that was not confirmed (for control group). For the genetic related group, children and adolescents were recruited within T1D families and were observed in a single time point, at the time of their brother/sister.

Description

Inclusion Criteria:

• T1D Group: children diagnosed with T1D, according to internationally defined criteria, with at least one positive pancreatic antibody and under functional insulin.
• Genetic-related group: children without T1D, age- and sex-matched with T1D group, recruited among T1D relatives;
• Control group: children without T1D, age- and sex-matched with T1D group, recruited from general endocrinology clinics, among children without disease or genetic relation with T1D children;

Exclusion Criteria:

• Obesity, according to WHO standards for pediatrics;
• Hypertension, as ≥95th percentile according to International Consensus;
• Other auto-immune diseases;
• Diabetes in the context of syndromic features/secondary to treatments;
• Hypothyroidism, adrenal insufficiency or hypercortisolism;
• Children under somatotropin/oncologic treatment;
• Under medications affecting glucose metabolism

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Type 1 Diabetes Group; Type 1 Diabetes people under 18 years´old	Diagnostic test: Blood and urine samples collection; Blood and urine were collected at a single time point for all participants, from the tree study groups. Fasting for blood collection and the first urine in the morning were required.
Genetic-related Group; Brothers/sisters of T1D children and adolescents (without disease)	Diagnostic test: Blood and urine samples collection; Blood and urine were collected at a single time point for all participants, from the tree study groups. Fasting for blood collection and the first urine in the morning were required.
Control group; Not genetic related and no T1D people under 18 years' old	Diagnostic test: Blood and urine samples collection; Blood and urine were collected at a single time point for all participants, from the tree study groups. Fasting for blood collection and the first urine in the morning were required.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine miRNAs extracellular vesicles molecular signatures for the study groups	Characterize urine EV-derived miRNAs in the three study groups	October/23 until July/2024
Blood miRNAs extracellular vesicles molecular signatures for the study groups	Characterize blood miRNAs extracellular vesicles molecular signatures for the study groups	October/23 until July/2024

Collaborators and Investigators

• Sponsor: Centro Hospitalar e Universitário de Coimbra, E.P.E.
• Collaborators: Università di Siena

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2023
• Primary Completion (Actual): October 15, 2023
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: February 12, 2025
• First Submitted That Met QC Criteria: February 12, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Non-invasive biomarker of beta cell function in urine
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: OBS.SF.05.2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Confidential information collected with permission for this study purpose but not to share with other studies

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No