Lactobacillus Johnsonii for Type 1 Diabetes

Overseen By Sarah Peeling

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: Antibiotics, Probiotics, Laxatives, Antidiarrheals

Disqualifiers: Gastrointestinal disease, Chronic kidney disease, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 24 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

While genetics demonstrated a major risk factor for the development of type 1 diabetes (T1D), microbiota dysbiosis has been suggested as an elicitor in immunological tolerance and of beta cell autoimmunity. The probiotic Lactobacillus johnsonii N6.2 may prevent or restore the gut flora and show systemic impacts and adaptive immunity in the T1D population thereby preserving beta cell function.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications for constipation or diarrhea, or if you have taken antibiotics in the past 2 weeks. If you are taking a probiotic supplement, you must stop at least 2 weeks before the study starts.

Is Lactobacillus johnsonii safe for humans?

Lactobacillus johnsonii N6.2 has been shown to be safe in healthy adults, with no significant changes in blood tests and a reduction in symptoms like abdominal pain and indigestion. It is well tolerated and has positive effects on the immune system, making it a feasible option for further studies. ^{1 2 3 4 5}

How is the treatment Lactobacillus johnsonii N6.2 unique for type 1 diabetes?

Lactobacillus johnsonii N6.2 is unique because it is a probiotic that may help prevent type 1 diabetes by changing the balance of certain substances in the body and supporting the immune system, unlike traditional treatments that focus on managing blood sugar levels. ^{3 4 6 7 8}

What data supports the effectiveness of the treatment Lactobacillus johnsonii N6.2 for type 1 diabetes?

Research shows that Lactobacillus johnsonii N6.2 can reduce the development of type 1 diabetes in diabetes-prone rats by affecting certain immune responses. Additionally, it is well tolerated in healthy adults and influences immune cell populations, suggesting potential benefits for preventing type 1 diabetes. ^{3 4 7 9 10}

Who Is on the Research Team?

Michael J Haller, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for children and adolescents with Type 1 Diabetes who can swallow capsules, provide blood and stool samples, complete online questionnaires, and take C-peptide tests. They must not have gastrointestinal diseases, recent antibiotic use, heart disease, live with immunocompromised individuals or be pregnant.

Inclusion Criteria

I can swallow pills.

I am willing to fill out weekly online questionnaires.

are willing to provide blood samples throughout the study

Exclusion Criteria

I have or am being treated for a condition that weakens my immune system.

You are allergic to milk or milk protein.

I am receiving treatment for chronic kidney disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive a daily capsule with Lactobacillus johnsonii N6.2 or placebo for 24 weeks

24 weeks

3 visits (in-person) at weeks 0, 12, and 24

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

1 visit (in-person) at week 48

What Are the Treatments Tested in This Trial?

Interventions

• Lactobacillus johnsonii N6.2

Trial Overview The study is testing whether the probiotic Lactobacillus johnsonii N6.2 can help maintain gut health and support immune function in young people with Type 1 Diabetes by comparing it to a placebo capsule.

How Is the Trial Designed?

Group I: Probiotic Group Active Control 1 Intervention

The probiotic group will receive a daily capsule with Lactobacillus johnsonii N6.2 1x109 CFUs. Participants will consume one capsule (treatment or placebo) daily for 24 weeks.

Group II: Placebo Group Placebo Group 1 Intervention

The placebo group will receive a capsule daily with dried skim milk (vehicle of the probiotic). Participants will consume one capsule (treatment or placebo) daily for 24 weeks.

Lactobacillus johnsonii N6.2 is already approved in United States for the following indications:

Approved in United States as Lactobacillus johnsonii N6.2 for:

• Type 1 Diabetes (T1D)

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

Published Research Related to This Trial

The complete genome sequences of Lactobacillus johnsonii strain N6.2 and Lactobacillus reuteri strain TD1 were reported, providing valuable genetic information about these beneficial intestinal bacteria.

Both strains were isolated from a type 1 diabetes-resistant rat model, suggesting their potential role in gut health and disease resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Genome Sequences of Lactobacillus johnsonii Strain N6.2 and Lactobacillus reuteri Strain TD1. Leonard, MT., Valladares, RB., Ardissone, A., et al.[2021]

In a double-blind, randomized trial involving 42 healthy participants over 8 weeks, Lactobacillus johnsonii N6.2 was found to be safe and well-tolerated, with no significant changes in metabolic or blood cell profiles.

The probiotic treatment led to increased serum tryptophan levels and a decreased kynurenine:tryptophan ratio, along with significant changes in immune cell populations, suggesting potential immunological benefits that could support its use in preventing type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus johnsonii N6.2 Modulates the Host Immune Responses: A Double-Blind, Randomized Trial in Healthy Adults. Marcial, GE., Ford, AL., Haller, MJ., et al.[2021]

In a study involving 96 children aged 8-17 with newly diagnosed type 1 diabetes, the probiotics Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 did not significantly improve beta-cell function compared to a placebo over a 6-month period.

While there were no severe adverse effects reported, the probiotic group showed a higher incidence of thyroid autoimmunity, although this was also present at baseline, indicating the need for further research to determine the safety and efficacy of these probiotics in managing type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomised controlled trial. Groele, L., Szajewska, H., Szalecki, M., et al.[2022]

Administering Lactobacillus johnsonii to diabetes-prone rats significantly delayed the onset of type 1 diabetes, suggesting a protective effect linked to changes in gut microbiota and host immune response.

The study found that L. johnsonii administration led to a healthier intestinal environment, characterized by reduced oxidative stress and lower levels of pro-inflammatory cytokines, indicating its potential as a therapeutic strategy for modulating diabetes development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats. Valladares, R., Sankar, D., Li, N., et al.[2022]

In a study of 40 patients with type 2 diabetes, supplementation with Lactobacillus casei 01 for 8 weeks led to significant reductions in dietary intake, body weight, and waist circumference compared to a placebo group.

The probiotic also improved glycemic control by decreasing fasting blood sugar, insulin levels, and insulin resistance, while increasing serum SIRT1 levels, suggesting a new mechanism of action for probiotics in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic assisted weight management as a main factor for glycemic control in patients with type 2 diabetes: a randomized controlled trial. Khalili, L., Alipour, B., Asghari Jafarabadi, M., et al.[2023]

Lactobacillus johnsonii Ncc533 (La1) did not significantly affect the immune response in normal mice from newborn to adult, as indicated by unchanged levels of IL-4 and IFN-γ in splenocytes.

In an asthma model, La1 treatment led to a significant reduction in IL-4 expressing cells and OVA-specific IgE levels compared to water-treated controls, suggesting that La1 may help regulate immune responses in allergic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of Lactobacillus johnsonii Ncc533 (La1) on the balance of Th1/Th2 cells in BALB/c mice. Yang, J., Li, W., Sun, R., et al.[2019]

In a study involving 71 infants aged 4-5 months, supplementation with the probiotic Lactobacillus johnsonii (La1) in formula did not lead to increased levels of D-lactate, indicating no risk of metabolic acidosis.

After 4 weeks, D-lactate levels in infants fed formula with La1 remained within normal ranges for healthy infants, suggesting that La1 is safe for use in infant formula without adverse effects on lactate metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary D-lactate excretion in infants receiving Lactobacillus johnsonii with formula. Haschke-Becher, E., Brunser, O., Cruchet, S., et al.[2009]

Oral administration of the probiotic Lactobacillus johnsonii La1 (LJLa1) for 2 weeks significantly inhibited hyperglycemia and reduced glucagon levels in diabetic rats, suggesting its potential as a treatment for glucose metabolism disorders.

LJLa1 appears to improve glucose tolerance by altering autonomic nerve activity, specifically by suppressing adrenal sympathetic nerve activity, which may lead to reduced glucagon secretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the probiotic strain Lactobacillus johnsonii strain La1 on autonomic nerves and blood glucose in rats. Yamano, T., Tanida, M., Niijima, A., et al.[2013]

The complete genome sequence of Lactobacillus johnsonii FI9785 has been reported, highlighting its potential as a probiotic due to its beneficial properties.

This strain has been shown to effectively prevent the colonization of Clostridium perfringens in specific-pathogen-free chicks, suggesting its efficacy in protecting against certain pathogens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete genome sequence of Lactobacillus johnsonii FI9785, a competitive exclusion agent against pathogens in poultry. Wegmann, U., Overweg, K., Horn, N., et al.[2022]

Lactobacillus johnsonii strain MR1, isolated from a mouse model, effectively reduces allergic airway inflammation when given orally, suggesting its potential as a therapeutic intervention for allergies.

The strain's genome was fully sequenced, revealing a single, closed genome of nearly 1.95 million base pairs, which provides valuable genetic information for understanding its mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Genome Sequence of Lactobacillus johnsonii MR1, Isolated from a BALB/c Mouse Cecum. Ravi, K., Rauch, M., Lynch, SV., et al.[2023]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Complete Genome Sequences of Lactobacillus johnsonii Strain N6.2 and Lactobacillus reuteri Strain TD1. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Lactobacillus johnsonii N6.2 Modulates the Host Immune Responses: A Double-Blind, Randomized Trial in Healthy Adults. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomised controlled trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Probiotic assisted weight management as a main factor for glycemic control in patients with type 2 diabetes: a randomized controlled trial. [2023]

6. Canada pubmed.ncbi.nlm.nih.gov

The effect of Lactobacillus johnsonii Ncc533 (La1) on the balance of Th1/Th2 cells in BALB/c mice. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Urinary D-lactate excretion in infants receiving Lactobacillus johnsonii with formula. [2009]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of the probiotic strain Lactobacillus johnsonii strain La1 on autonomic nerves and blood glucose in rats. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Complete genome sequence of Lactobacillus johnsonii FI9785, a competitive exclusion agent against pathogens in poultry. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Complete Genome Sequence of Lactobacillus johnsonii MR1, Isolated from a BALB/c Mouse Cecum. [2023]