The Effect of Probiotics on Type 1 Diabetes Mellitus in Children

NCT ID: NCT03880760

Last Updated: 2021-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-01
• Study Completion Date: 2021-01-31

Brief Summary

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.

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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32

Intervention Type: OTHER

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 capsule

Taking 1 placebo capsule twice a day before meals for six months.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Taking 1 placebo capsule twice a day before meals for six months.

Interventions

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.

Intervention Type: OTHER

Placebo

Taking 1 placebo capsule twice a day before meals for six months.

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

China Medical University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Chung-Hsing Wang

Attending physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hung-chih Lin

Role: STUDY_DIRECTOR

China Medical University Hospital

Locations

China Medical University Hospital

Taichung, , Taiwan

Countries

Taiwan

References

Wang CH, Yen HR, Lu WL, Ho HH, Lin WY, Kuo YW, Huang YY, Tsai SY, Lin HC. Adjuvant Probiotics of Lactobacillus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, and Bifidobacterium animalis subsp. lactis CP-9 Attenuate Glycemic Levels and Inflammatory Cytokines in Patients With Type 1 Diabetes Mellitus. Front Endocrinol (Lausanne). 2022 Mar 1;13:754401. doi: 10.3389/fendo.2022.754401. eCollection 2022.

Reference Type: DERIVED

PMID: 35299968 (View on PubMed)

Other Identifiers

CMUH107-REC2-036

Identifier Type: -

Identifier Source: org_study_id