Determinants of Glycaemic Control in Children With Type 1 Diabetes

NCT06325111 | Recruiting

• 1 other identifier: RC 06/2023
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

Type 1 diabetes (T1D) is a common chronic disease of childhood associated with a significantly increased risk of micro- and macro-vascular complications, including neuropathy, nephropathy and cardiovascular diseases. The risk of development T1D comorbidities is associated with glycaemic control, a complex mechanism involving biological, physiological environmental factors. While more than 60 genetic variants were already associated with Glycated hemoglobin (HbA1c) in healthy subjects, very few genes have been identified in T1D individuals. Also, hyperglycaemia could be the cause of epigenetic changes at specific target genes, such as DNA methylation, histone modifications and microRNAs, correlated to accelerated development of diabetes-related complications. Most recently, increasing evidence also suggested that human microbiome may play a crucial role in the onset and progression of T1D and dysbiosis of the gut and oral microbiota was reported as a typical feature of hyperglycaemia. However, potential differences among poorly and good managed T1D subjects have not been still studied. Also, the exact mechanism by long-term hyperglycaemia's acts in T1D remains poorly understood. Therefore, this project will explore an emerging area of research by the study of possible genetic, epigenetic and environmental biomarkers among T1D subjects with different glycaemic control.

Conditions

Diabetes Mellitus, Type 1

Keywords

Type 1 Diabetes glycaemic control; Epigenetic modifications; Diabetes-related complications

Outcome Measures

Primary Outcomes (4)

• Identification of genes involved in T1D glycaemic control

  DNA will be isolated from saliva by Genefix Saliva DNA/RNA collection kit (Isohelix, UK) and whole genome genotyping will be performed using Illumina chip arrays (CA, USA).

  Through study completion, an average of 18 months

• Identification of DNA methylation patterns involved in T1D glycaemic control

  Peripheral blood will be collected from each participant into EDTA-containing tubes and Genome-wide DNA methylation will be performed using the Illumina Infinium Human Methylation EPIC BeadChip array

  Through study completion, an average of 18 months

• Identification of microRNAs involved in T1D glycaemic control

  Peripheral blood will be collected from each participant into Ethylenediaminetetraacetic acid (EDTA)-containing tubes for microRNAs sequencing. Illumina TruSeq Small RNA Sample Preparation kit will be used for library preparation, and sequencing will be conducted by Illumina platform (CA, USA).

  Through study completion, an average of 18 months

• Identification of oral microbiome characteristics associated to T1D glycaemic control

  Bacterial DNA will be extracted from saliva and a 500 base pair region of the V1-V3 portion of the 16S ribosomal RNA gene as well as the 200 base pair region of the V3 portion will be amplified. The V3 amplicon will be used for template preparation and will be sequenced using the Ion PGM Hi-Q View sequencing kit (Life Technologies, New York, NY, USA) with the IonPGM™System technology

  Through study completion, an average of 18 months

Study Arms (2)

Patients with T1D and optimal glycaemic control

Optimal glycaemic control will be defined as HbA1c values \<7%

Other: Determinants of T1D glycaemic control

Patients with T1D and poor glycaemic control

Poor glycemic control will be defined as HbA1c value ≥7%

Other: Determinants of T1D glycaemic control

Interventions

Determinants of T1D glycaemic control OTHER

DNA genotyping, microbiome, DNA methylation and microRNAs analysis

Patients with T1D and optimal glycaemic control; Patients with T1D and poor glycaemic control

Eligibility Criteria

• Age: 6 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

T1D subjects (children and young adults) attending to several Diabetes Units of Italian and European institutions

You may qualify if:

• Type 1 diabetes subjects
• Age from 6 to 20 years old
• At least 5 years of duration of disease

You may not qualify if:

• Type 1 diabetes subjects incapable of giving valid informed consent or whose parents are incapable of giving valid informed consent.
• Type 1 diabetes subjects for whom it is not possible to collect information on the clinical history, starting from the onset of diabetes
• Subjects with other types of diabetes (i.e. type 2, monogenic diabetes, cystic fibrosis related diabetes)

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead

Study Sites (1)

Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"

Trieste, 34137, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood and saliva samples

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Complications

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Eulalia Catamo, BSc

CONTACT

040.3785470; eulalia.catamo@burlo.trieste.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: March 22, 2024
• Study Start: May 29, 2023
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: March 22, 2024

Record last verified: 2024-03

Locations

IT (1)