Evaluation of an Anti-inflammatory Diet in Autoimmune and Metabolic Diseases

Sponsor

IRCCS San Raffaele (Other)

Overall Status

Recruiting

CT.gov ID

NCT05766657

Collaborator

(none)

Enrollment

Locations

Arms

11.3

Anticipated Duration (Months)

Patients Per Site

3.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The overall objective of the study is to provide personalized nutritional advice based on the gut microbiota profile of children with type 1 diabetes (T1D) or obesity.

Specifically, the primary objective of NUTRI-DIET is to validate a dietary model aimed at restoring bacterial species and/or anti-inflammatory metabolites in order to prevent extra-intestinal diseases characterized by dysbiosis, such as T1D and obesity.

The primary endpoints of the study will be to monitor the glycemic control indices, i.e., blood glucose (mean of glycemic values, percentage of time-in-range value (TIR), which will be displayed by glycemic sensor) and glycated hemoglobin for diabetic children and Body mass index (BMI) z-score according to World Health Organization (WHO) recommendations (WHO BMI-for-age boys; WHO BMI-for-age girls) for obese children.

The secondary objective of the study is to characterize the microbiota profile of the study patients and to test the algorithm under development built from the integration of diet and and gut microbiota composition data that were obtained during the previous observational study NUTRI-T1D.

Condition or Disease	Intervention/Treatment	Phase
Type1 Diabetes Obesity	Dietary Supplement: Microbiome-targeted diet Dietary Supplement: Usual care diet	N/A

Detailed Description

Randomized, multicenter, 2-arm, parallel-group, single-blind controlled clinical trial (1:1 allocation ratio) with 1 group of patients with obesity (N=20) or type 1 (n=20) treated with standard obesity treatment diet or usual diet (diabetic children) and 1 group (N=20 for obesity and (N=20 for type 1 diabetes) treated with the same diets to which nutritional advice derived from microbiota analysis (NUTRI-DIET) will be added.

The study will last 12 months with an intervention phase (personalized diet) lasting 3 months.

The research includes an enrollment phase that may extend up to 9 months depending on the number of patients enrolled. The enrollment phase will be considered finished once a total of 80 patients (i.e., 40 pediatric patients with type 1 diabetes and 40 obese pediatric patients) are enrolled. During the patient enrollment phase, relevant clinical information (biological samples as faeces, urines and blood and questionnaires on diet habits, physical activity and stress) will be collected concurrently. Tests will be performed once enrollment is completed on samples from all patients collected at the time of enrollment (microbiota analysis on stool, metabolome analysis on stool and urine, serological gut barrier markers analysis on serum). Obese and/or diabetic children will be randomized to the intervention or control group. Randomization will be done according to age (≤12: >12), gender and pathology (diabetes or obesity).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, multicenter, 2-arm, parallel-group, single-blind controlled clinical trial (1:1 allocation ratio)Randomized, multicenter, 2-arm, parallel-group, single-blind controlled clinical trial (1:1 allocation ratio)

Masking:

Double (Participant, Care Provider)

Masking Description:

Single blind: Apart from clinical nutritionists who will be involved in dietary counseling, physicians and all project staff who will be responsible for patient selection and follow-up, along with biostatisticians, will be blinded to the intervention groups.

Primary Purpose:

Treatment

Official Title:

Evaluation of the Effect of an Anti-inflammatory Diet Built on the Basis of the Gut Microbiota in Children With Type 1 Diabetes and Obesity

Actual Study Start Date :

Dec 23, 2022

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention group Children with obesity or T1D will be randomized into this group. An individualized dietary approach will be used in this group of children.	Dietary Supplement: Microbiome-targeted diet The gut microbiota (on stool) and metabolic profile (on stool and urine) will be analyzed at time 0, and the dietary plan will contain specific directions aimed at restoring a proper metagenomic and metabolomic profile of the microbiota.
Placebo Comparator: Control Group children assigned to the control group will receive generic advice based on European dietary guidelines for obesity or follow their usual diet in the case of children with T1D.	Dietary Supplement: Usual care diet Subjects on the control group will receive general dietetic advice for Obesity or T1D

Arm

Intervention/Treatment

Experimental: Intervention group

Children with obesity or T1D will be randomized into this group. An individualized dietary approach will be used in this group of children.

Dietary Supplement: Microbiome-targeted diet

The gut microbiota (on stool) and metabolic profile (on stool and urine) will be analyzed at time 0, and the dietary plan will contain specific directions aimed at restoring a proper metagenomic and metabolomic profile of the microbiota.

Placebo Comparator: Control Group

children assigned to the control group will receive generic advice based on European dietary guidelines for obesity or follow their usual diet in the case of children with T1D.

Dietary Supplement: Usual care diet

Subjects on the control group will receive general dietetic advice for Obesity or T1D

Outcome Measures

Primary Outcome Measures

Glycemia [Up to 3 months]
Blood glucose levels (mg/dL) will be measured in diabetic children.
Glycemic control by glycated hemoglobin (HbA1c) monitoring [Up to 3 months]
The percentage of glycated hemoglobin (HbA1c, %) in the blood will be measured in diabetic children.
Glycemic control by Time-in-Range (TIR) monitoring [Up to 3 months]
TIR values - that is the percentage of time in which blood glucose (blood sugar) remains in the safe target range of 70-180mg/dL - will be monitored in diabetic children by extracting the recorded data from the continuous glucose monitoring (CGM) device (sensor).
Body mass index (BMI) [Up to 3 months]
The BMI z-score in obese children will be measured, according to WHO recommendations (WHO BMI-for-age boys; WHO BMI-for-age girls).

Secondary Outcome Measures

Metagenomic analysis [Up to 3 months]
Changes in gut microbiota composition following personalized microbiome-targeted diet, as assessed by 16S ribosomal RNA (rRNA) sequencing on DNA extracted from patient-derived fecal samples.
Metabolomic analysis [Up to 3 months]
Changes in microbiota-derived metabolites following personalized microbiome-targeted diet, as assessed by Mass Spectrometry on patient-derived fecal and urine samples.

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eligible for participation will be children diagnosed with obesity (BMI > 95th percentile) and type 1 diabetes aged 8-18 years
Signature of informed consent

Exclusion Criteria:

Children with any acute or chronic disease (cancer, infection, other), gastrointestinal disease, cardiovascular disease, chronic kidney disease, parathyroid disease, diseases requiring regular phlebotomies, and other chronic diseases that could affect the results of the present study
Taking medications other than insulin, including hypolipidemic and antihypertensive drugs
Use of medications that could affect the results of the study, including systemic glucocorticoids and antibiotics (in the three months prior to the study)
Recent weight loss or weight gain (> 3 kg), (in the 3 months preceding the study)
Blood transfusion in the last 3 months prior to blood sampling
Use of dietary supplements, including multivitamins, fish oil capsules, minerals and trace elements (three months prior to and throughout the study period)
Inability (physically or psychologically) to comply with the procedures required by the protocol
Children with specific eating disorders, which may hinder the research results