The Effect of Probiotics on Type 1 Diabetes Mellitus in Children

August 2, 2021 updated by: Chung-Hsing Wang, China Medical University Hospital
In this study, investigators try to administer probiotics (Lactobacillus salivarius + Lactobacillus johnsonii + Bifidobacterium lactis from glac biotech Co., Ltd.) to children T1DM patients for 6 months to observe if the inhibition effect of T1DM animal model could be discerned in a short-term period from both change of serum cytokines and beta cells insulin secretion ability.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Type 1 (insulin-dependent) Diabetes Mellitus (T1DM) is among the most well studied organ-specific autoimmune diseases which approximately 75% of newly diagnosed DM patients acquire this type before the age of 18. T1DM is well known for as the consequence of selective destruction of pancreatic insulin-producing beta cells within the islets of Langerhans. Basically, autoimmune reactions against beta cells may come from activation of the immune system in genetically susceptible individuals triggered by environmental factors that bear epitopes similar to those expressed by the beta cells. Several mechanisms such as molecular mimicry, metabolic stress on beta cells, cryptic epitope exposure and costimulatory molecule upregulation have been proposed but none of them could be solely responsible for the pathogenesis of T1DM. Recently, T1DM has been considered a consequence of dysregulated or over-activation of immune responses in genetically predisposed individuals, similar to other autoimmune diseases.

The rapid increase in the incidence of T1DM in developed countries including Taiwan during recent decades refers to the role of environmental factors in this disease. Candidate environmental factors influencing T1DM include various microbial and food components encountered at mucosal surfaces as well as gut mucosal parameters such as gut permeability. However, difficulty exists in characterizing the environmental factors and mechanisms in T1DM because of their complexity of interaction, the long lag period between the induction of disease trigger factors and the clinical onset of the disease. Environmental factors in T1DM seem to prevent full penetration of the disease rather than trigger it. It had been reported that high diabetes incidence in germ-free mice and an involvement of innate immune mechanisms in the disease. In this study, investigators try to administer probiotics (Lactobacillus salivarius + Lactobacillus johnsonii + Bifidobacterium lactis from glac biotech Co., Ltd.) to children T1DM patients for 6 months to see if the inhibition effect of T1DM animal model could be discerned in a short-term period from both change of serum cytokines and beta cells insulin secretion ability.

Subjects will collect blood before the test and every 3 months after the test for total 4 times. Each time the collected blood volume is about 5~8cc. A part of the blood sample will be given to the Department of laboratory medicine for the detection of hemoglobin A1c (HbA1c) and fasting blood glucose, and the other part will be centrifuged to separate serum. The serum macrophage inflammatory proteins-1beta (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), interleukin-8 (IL-8), interleukin-17 (IL-17), tumor necrosis factor alpha (TNF-α) and transforming growth factor beta1 (TGF-β1) concentrations will be measured by ELISA.

Study Type

Interventional

Enrollment (Actual)

64

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taichung, Taiwan, 40447
        • China Medical University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age between 6 to 18 years old.
  2. T1DM patients confirmed by glucagon tests and/or presence of autoantibody(ies).

Exclusion Criteria:

  1. Significant cardiac, renal and hepatic disease.
  2. The physician diagnosed the immunodeficiency or the immune function was low.
  3. Currently using probiotics supplements or had ever taken probiotics for more than one month.
  4. Currently using antibiotics or gastrointestinal medicine.
  5. Ever allergic reaction(s) to probiotics or prebiotics regimen.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Probiotics capsule
Taking 1 L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32 mix probiotics capsule twice a day before meals for six months.
Other: L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32
Taking 1 L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32 mix probiotics capsule twice a day before meals for six months.
PLACEBO_COMPARATOR: Placebo capsule
Taking 1 placebo capsule twice a day before meals for six months.
Other: Placebo
Taking 1 placebo capsule twice a day before meals for six months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in percentage of HbA1c
Time Frame: From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Subjects will draw blood once before the test. During the test, every 3 months will draw blood to 6th month, each time the blood volume is about 5 ~ 8cc to detect HbA1c and other blood biochemical values.
From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Change in concentration of blood glucose (AC)
Time Frame: From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
The study will require subject to record their own daily fasting blood glucose.
From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in concentration of MIP-1β
Time Frame: From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Serum was isolated by extra blood draw, serum MIP-1β (pg/ml) concentrations were measured from first blood draw to third blood draw by ELISA.
From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Change in concentration of RANTES
Time Frame: From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Serum was isolated by extra blood draw, serum RANTES (pg/ml) concentrations were measured from first blood draw to third blood draw by ELISA.
From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Change in concentration of IL-8
Time Frame: From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Serum was isolated by extra blood draw, serum IL-8 (pg/ml) concentrations were measured from first blood draw to third blood draw by ELISA.
From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Change in concentration of IL-17
Time Frame: From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Serum was isolated by extra blood draw, serum IL-17 (pg/ml) concentrations were measured from first blood draw to third blood draw by ELISA.
From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Change in concentration of TNF-α
Time Frame: From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Serum was isolated by extra blood draw, serum TNF-α (pg/ml) concentrations were measured from first blood draw to third blood draw by ELISA.
From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Change in concentration of TGF-β1
Time Frame: From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Serum was isolated by extra blood draw, serum TGF-β1 (pg/ml) concentrations were measured from first blood draw to third blood draw by ELISA.
From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

China Medical University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 1, 2018

Primary Completion (ACTUAL)

October 31, 2020

Study Completion (ACTUAL)

January 31, 2021

Study Registration Dates

First Submitted

March 13, 2019

First Submitted That Met QC Criteria

March 18, 2019

First Posted (ACTUAL)

March 19, 2019

Study Record Updates

Last Update Posted (ACTUAL)

August 4, 2021

Last Update Submitted That Met QC Criteria

August 2, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMUH107-REC2-036

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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