Microbiome in the Acute Stage of New Onset Paediatric Type 1 Diabetes

The goal of this observational study is to learn more about the microbiome and metabolome of children with type 1 diabetes (T1D). The main questions it aims to answer are:

1. Do the microbiome and metabolome play a role in the onset and presentation of T1D?
2. How do the microbiome and metabolome evolve during the early stages of T1D?
3. Are there are differences in the microbiome or metabolome of children who present with diabetic ketoacidosis (DKA) versus those who present without DKA, and between those who present with mild, moderate or severe DKA?
4. Is there an association between the microbiome or metabolome and glycaemic control during the first year of diagnosis?

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes

Detailed Description

T1D is caused by autoimmune-mediated destruction of pancreatic beta cells. This leads to a complete deficiency of insulin. Individuals diagnosed with T1D require life-long exogenous insulin replacement to achieve glucose homeostasis and, ultimately, to survive. Although there is an underlying genetic predisposition to developing T1D, the trigger is multifactorial and likely includes environmental factors.

Several large cohort studies have identified differences in the microbiome in those with T1D compared to healthy controls and suggested that it may have a role in the pathogenesis of T1D. It is not yet clear if changes in the microbiome are involved in the pathogenesis of beta-cell destruction or are an effect of the disease state.

When children present with T1D for the first time, their blood glucose levels are elevated. Some children will present with life threatening DKA in which there is metabolic dysfunction and, in some cases, end organ damage.

This study will examine the microbiome and metabolome of children with newly diagnosed T1D during their initial hospital admission, and describe the changes that occur in the microbiome and metabolome as these individuals are commenced on insulin and return to normal glucose homeostasis.

The study will also compare the microbiome and metabolome of children presenting with and without DKA to establish if there are particular patterns of microbial diversity which are more common in one group. The study also aims to establish if there us an association between the microbiome or metabolome and glycaemic control during the first year of T1D diagnosis

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Colin Hawkes; Phone Number: +353(0)21 4205082; Email: chawkes@ucc.ie
• Study Contact Backup: Name: Elaine Kennedy; Email: elainekennedy@ucc.ie

Study Locations

• Ireland
  • Cork, Ireland
    • Recruiting
    • Cork University Hospital
    • Contact: Colin Hawkes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

All children aged between 6 months and 18 years who are admitted to hospital with a new diagnosis of T1D will be assessed for eligibility for enrolment to this study.

Healthy siblings will be assessed for eligibility to be enrolled as controls in this study

Description

Inclusion Criteria:

1. Males and females with newly diagnosed T1D.
2. Aged between 6 months and 18 years at their first study visit.
3. Consent provided by parent/guardian to participate in this study.
4. Age dependent assent or consent obtained for participants aged 6-18 years

Exclusion Criteria:

1. Individuals who have a known diagnosis of inflammatory bowel disease or another medical condition which the study team deems might interfere with the microbiome.
2. Individuals with complex medical or behavioural needs that would deem the participant unable to participate in the study.
3. Have a significant acute or chronic co-existing illness (cardiovascular, gastrointestinal, endocrinological, immunological, metabolic) or any condition which contraindicates entry to the study according to the investigator's judgement.
4. Participants who are receiving treatment involving experimental medications.
5. If the participant took part in a recent experimental trial, the trial must have been completed not less than 30 days prior to participation in this study.
6. Have a malignant disease or any concomitant end-stage organ disease

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cases; Children with newly diagnosed T1D
Controls; Healthy siblings of cases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe evolution of the microbiome and metabolome during the early stages of new onset T1D	Microbiome biodiversity in cases vs controls	52 weeks

Collaborators and Investigators

• Sponsor: University College Cork
• Collaborators: APC Microbiome Ireland
• Investigators: Principal Investigator: Colin Hawkes, University College Cork

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2023
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: November 27, 2023
• First Submitted That Met QC Criteria: November 27, 2023
• First Posted (Actual): December 6, 2023

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: Acute T1D

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No