Clinical trial NCT05521061: The Effect of Human Milk Oligosaccharides in Children With Type 1 Diabetes Mellitus
Official title: The Effects of Synthetic Human Milk Oligosaccharides on Gut Microbiota, Pancreas Beta Cell Preservation and Metabolic Control in Children With Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus
Type1diabetes
Keywords: Diabetes mellitus
intestinal microbiota
oligosaccharides
human milk
Lead sponsor: Ege University
Sponsor class: OTHER
Collaborators: name: Acibadem University
name: Eskisehir Osmangazi University
First posted: 2022-08-30
Enrollment: 111
Sex: ALL
Minimum age (years): 4
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Type 1 diabetes mellitus (DM) is an autoimmune disease characterized by absolute insulin deficiency, defined as insulin-dependent diabetes mellitus and develops due to autoimmune damage of beta cells in the pancreas. Approximately 425 million people worldwide are diabetic patients, 5% to 10% of whom are T1DM. In the majority of type 1 DM prevention studies, the main aim is to stop beta cell destruction. Primary prevention studies aim to prevent or alter exposure to environmental stimuli before autoimmunity is developed. Secondary prevention studies address interventions in the autoimmune processes that cause betacell destruction. Tertiary prevention studies include interventions to stop or reverse beta-cell destruction after clinical diagnosis of type 1 DM. Despite all technological advances, type1DM has not shown a permanent improvement in metabolic control over the last 5 years. Breast milk provides protection against Type 1 DM through the prevention of diabetogenic infections, delaying exposure to diet antigens including cow's milk, and the ability to produce healthy intestinal microbiota. Xiao et al. (2018) published in Nature, investigated the effect of human milk oligosaccharides on non-obese diabetic rats, where it was found that it improved intestinal flora and insulitis scores and brought the blood glucose level closer to the optimum level.

This study is expected to fill the gap in the literature about dose-dependent efficacy and placebo of breastmilk oligosaccharides in diabetic humans. This project will investigate 1) the possible contribution of 2-FL oligosaccharides to the disease's metabolic control 2) their effects on beta-cell preservation in the pancreas 3)their effects on intestinal microbiota 4) whether there is a doseresponse relationship as compared to placebo among type 1 diabetic children. This project is designed as a double-blind randomized placebo-controlled experiment lasting for 36 months. The proposed research population consists of 111 children aged 4-16-year-old who were diagnosed with Type 1 DM at the Department of Pediatric Endocrinology of Ege University. The sample size was calculated as 111 with an effect size of 0.33, an error of 0.05 and a power of 80% using the F-test group (for a numerical variable such as blood glucose) for 3 groups. It is planned that the two intervention arms consist of 37 volunteers and the placebo group of 37 volunteers. In the research, 1.5 g/day of human milk oligosaccharides will be supplemented in the first intervention group and 3 g/day for the second intervention group. The placebo group will receive maltodextrin as a placebo at a dose with no effect on metabolic control. Patients included in the study will be provided human milk oligosaccharides for 3 months and will be under follow-up for 12 months. All variables, mainly C-peptide, HbA1c, immunoglobulins, lymphocytes and faecal analysis will be examined. The project aims to ameliorate the microbiota profile, optimize C-peptide levels, reduce exogenous insulin dependence through the provision of 2-FL from human milk oligosaccharides and develop a more applicable, acceptable and an innovative method in the metabolic control of the disease. It is believed that the psychosocial and economic burdens of the disease will be reduced by increasing the metabolic control of the disease.


Eligibility criteria: Inclusion Criteria:

* Being at least 48 months of age
* Diagnosis period \<100 days, in the early stage
* Exogenous insulin requirement \> 0.5 U/kg/day in the late-stage
* Positive at least one autoantibody associated with type 1 DM (ICA, IAA, GADA)
* C-peptide level \<0.2 nmol/L during MMTT
* Between the 3rd percentile and the 97th percentile weight for age (between -2SD and +2SD)

Exclusion Criteria:

* Being breastfed despite the age of 48 months
* Failure to meet the diagnostic criteria for autoimmune type 1 DM (autoantibody negative)
* Co-morbidity illness
* To have taken antibiotics, probiotics, prebiotics and inflammatory drugs in the last one month before participating in the study or during the study

Primary outcomes:
measure: C peptide level
timeFrame: 12 weeks
measure: HbA1C levels
timeFrame: 12 weeks
Secondary outcomes:
measure: Pancreas autoantibody levels
timeFrame: 12 weeks
measure: Total daily dose of insulin
timeFrame: 12 weeks
Other outcomes:
Locations:
city: İzmir
country: Turkey
facility: Ege University
state: Bornova
Study officials:
References: