Type 1 Diabetes MellitusNCT03880760
The Effect of Probiotics on Type 1 Diabetes Mellitus in Children
A study testing L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32 in people with Type 1 Diabetes Mellitus, run by China Medical University Hospital at 1 site in Taiwan.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Aug 2018to 31 Jan 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age between 6 to 18 years old.
- T1DM patients confirmed by glucagon tests and/or presence of autoantibody(ies).
Who cannot join
- Significant cardiac, renal and hepatic disease.
- The physician diagnosed the immunodeficiency or the immune function was low.
- Currently using probiotics supplements or had ever taken probiotics for more than one month.
- Currently using antibiotics or gastrointestinal medicine.
- Ever allergic reaction(s) to probiotics or prebiotics regimen.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32, Placebo
- Keywords
- T1DM, Autoimmune diseases, Microbiota, Probiotics
- Medical subject headings
- Diabetes Mellitus, Type 1, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32Other
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.
PlaceboOther
Taking 1 placebo capsule twice a day before meals for six months.
| Study group | Role | What they receive |
|---|---|---|
| Probiotics capsule | Experimental | 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. Receives: Other: L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32 |
| Placebo capsule | Placebo comparator | Taking 1 placebo capsule twice a day before meals for six months. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in percentage of HbA1c
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.
Measured: 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)
The study will require subject to record their own daily fasting blood glucose.
Measured: From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Secondary outcomes (6)
Change in concentration of MIP-1β
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.
Measured: 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
Serum was isolated by extra blood draw, serum RANTES (pg/ml) concentrations were measured from first blood draw to third blood draw by ELISA.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: From date of first blood draw after entering the trial until the date of third blood draw, assessed up to 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2019
- Study start1 Aug 2018
- Primary completion31 Oct 2020
- Study completion31 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by China Medical University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Probiotics or placebo group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- China Medical University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chung-Hsing Wang, China Medical University Hospital
- Investigators
- Hung-chih Lin, Study director, China Medical University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03880760
- Sponsor's protocol ID
- CMUH107-REC2-036
- Status last verified
- Aug 2021
- First submitted
- 13 Mar 2019
- Last updated
- 4 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 35299968
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Probiotics on Type 1 Diabetes Mellitus in Children
- ClinicalTrials.gov ID
- NCT03880760
- Acronym / sponsor ID
- CMUH107-REC2-036
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- T1DM, Autoimmune diseases, Microbiota, Probiotics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- China Medical University HospitalUniversity, hospital or other
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 31 Oct 2020 (actual)
- Study completion
- 31 Jan 2021 (actual)
- First posted
- 19 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Probiotics or placebo group
| Arm | Type | Receives |
|---|---|---|
| Probiotics capsule | Experimental | Other: L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32Taking 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 | Placebo comparator | Other: PlaceboTaking 1 placebo capsule twice a day before meals for six months. |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Age between 6 to 18 years old.
- T1DM patients confirmed by glucagon tests and/or presence of autoantibody(ies).
Key exclusion criteria (5 listed)
- Significant cardiac, renal and hepatic disease.
- The physician diagnosed the immunodeficiency or the immune function was low.
- Currently using probiotics supplements or had ever taken probiotics for more than one month.
- Currently using antibiotics or gastrointestinal medicine.
- Ever allergic reaction(s) to probiotics or prebiotics regimen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32Taking 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 | Probiotics capsule |
| PlaceboTaking 1 placebo capsule twice a day before meals for six months. | Other | Placebo capsule |
Primary outcome
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.
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.
6 secondary outcomes
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.
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.
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.
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.
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2021.
- Derived from this study: PubMed 35299968Wang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hung-chih Lin study director
China Medical University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L. johnsonii MH-68, B. animalis subsp. lactis CP-9 and L. salivarius AP-32 in people with Type 1 Diabetes Mellitus, run by China Medical University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03880760, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2021.