Lactobacillus Johnsonii Probiotic for Type 1 Diabetes

Overseen By Sarah Peeling, BS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: Antibiotics, Probiotics, Laxatives

Disqualifiers: Gastrointestinal disease, Chronic kidney disease, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a probiotic called Lactobacillus johnsonii N6.2 to determine its potential benefits for people with Type 1 diabetes by improving gut health and supporting the immune system. The researchers aim to discover if this probiotic can protect the insulin-producing cells in the pancreas. Participants will take either the probiotic or a placebo (a capsule resembling the probiotic but without an active ingredient) daily for 24 weeks. This trial may suit individuals diagnosed with Type 1 diabetes who do not have other major health issues. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant diabetes research.

Will I have to stop taking my current medications?

The trial requires you to stop taking any probiotic supplements at least 2 weeks before starting. If you are taking medications for constipation or diarrhea, you cannot participate. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that Lactobacillus johnsonii N6.2 is likely to be safe for humans?

Research shows that Lactobacillus johnsonii N6.2, the probiotic under testing, appears safe. Studies have found it safe for healthy adults, with participants showing no significant changes in blood tests and some reporting fewer symptoms like stomach discomfort.

Previous research examined the probiotic's effects on the immune system and diabetes in animals. Although more data from human trials would be ideal, it is encouraging that no major safety issues have emerged so far. This suggests the treatment is generally well-tolerated in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for type 1 diabetes?

Unlike the standard treatments for Type 1 diabetes, which typically involve insulin therapy, Lactobacillus johnsonii N6.2 is a probiotic that aims to modulate the immune system. Researchers are excited about this treatment because it uses a unique mechanism by harnessing beneficial bacteria to potentially reduce inflammation and autoimmune activity. This approach could offer a novel way to manage Type 1 diabetes, potentially improving patients' quality of life by complementing existing therapies.

What evidence suggests that Lactobacillus johnsonii N6.2 might be an effective treatment for type 1 diabetes?

Research has shown that Lactobacillus johnsonii N6.2, a type of probiotic, may help manage type 1 diabetes (T1D). In studies with rats prone to developing diabetes, this probiotic altered gut bacteria and delayed the onset of T1D. It also helped control blood sugar levels and reduced pancreatic damage. The probiotic improves gut health and affects the immune system, potentially protecting insulin-producing cells. Although more human studies are needed, early results are promising for those at risk of or managing T1D. Participants in this trial will receive either Lactobacillus johnsonii N6.2 or a placebo to further evaluate its effects in humans. ^{1 2 3 4 5}

Who Is on the Research Team?

Michael J Haller, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

Adults with confirmed Type 1 Diabetes who can swallow capsules, provide blood and stool samples, take tests, complete weekly questionnaires online, and consume a daily capsule for 24 weeks. Excluded are those allergic to milk proteins, living with immunocompromised individuals, having immune-compromising diseases or conditions (like HIV/AIDS), chronic kidney disease, heart disease or taking certain medications.

Inclusion Criteria

I am willing to undergo three 2-hour meal tests.

Your blood and overall health tests must be normal, except for fasting glucose and HbA1c tests.

Are willing to provide blood samples throughout the study

Exclusion Criteria

I have taken antibiotics within the last 2 weeks.

I am pregnant, breastfeeding, or plan to become pregnant soon.

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

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)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Lactobacillus johnsonii N6.2

Trial Overview The trial is testing whether the probiotic Lactobacillus johnsonii N6.2 can improve gut flora and affect immunity in people with Type 1 Diabetes to help preserve beta cell function. Participants will either receive this probiotic or a placebo capsule without knowing which one they're getting.

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+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

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]

Lactobacillus johnsonii (Ljo) N6.2 significantly enhances the mucosal inflammatory response by inducing the expression of key chemokines and activating specific Toll-like receptors (TLRs), particularly TLR7 and TLR9, in intestinal cells.

The study suggests that the beneficial effects of Ljo N6.2 in mitigating type 1 diabetes may be linked to its ability to stimulate immune responses in the gut, indicating that probiotics could potentially be replaced with specific cellular components for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus johnsonii N6.2 stimulates the innate immune response through Toll-like receptor 9 in Caco-2 cells and increases intestinal crypt Paneth cell number in biobreeding diabetes-prone rats. Kingma, SD., Li, N., Sun, F., et al.[2023]

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]

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]

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]

Supplementation with probiotics Lacticaseibacillus paracasei SD1 and Lacticaseibacillus rhamnosus SD11 significantly improved various health markers in diabetic mice, including body weight, glycemic levels, and insulin levels over an 8-week period.

Both probiotics reduced inflammation and protected pancreatic β-cells by modulating immune responses, with SD11 showing superior effects in stabilizing glycemic levels and enhancing β-cell survival compared to SD1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotics of Lacticaseibacillus paracasei SD1 and Lacticaseibacillus rhamnosus SD11 attenuate inflammation and β-cell death in streptozotocin-induced type 1 diabetic mice. Nopparat, J., Khuituan, P., Peerakietkhajorn, S., et al.[2023]

Five strains of Lacticaseibacillus rhamnosus, isolated from traditional Greek foods, showed promising probiotic properties that could help maintain gut health and potentially alleviate symptoms of type 1 diabetes (T1D).

These strains demonstrated significant inhibitory effects on harmful bacteria and α-glucosidase activity, suggesting they could serve as a natural alternative to traditional antidiabetic medications, although further testing in animal models is needed to confirm their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Wild-Type Lacticaseibacillus rhamnosus Strains as Candidates to Manage Type 1 Diabetes. Nelios, G., Santarmaki, V., Pavlatou, C., et al.[2022]

A 3-month treatment with Lactobacillus rhamnosus GG (LGG) did not significantly enhance the immune response to the quadrivalent inactivated influenza vaccine (QIV) in children and adolescents with type 1 diabetes, as shown in a study involving 64 participants.

However, the combination of QIV and LGG led to reduced inflammatory responses without affecting the production of protective antibodies, indicating that while LGG may not boost vaccine efficacy, it can help manage inflammation in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of probiotic administration on immune responses of children and adolescents with type 1 diabetes to a quadrivalent inactivated influenza vaccine. Bianchini, S., Orabona, C., Camilloni, B., 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5466969/

Lactobacillus johnsonii N6.2 Modulates the Host Immune ... Lactobacillus johnsonii N6.2 mitigates the onset of type 1 diabetes (T1D) in biobreeding diabetes-prone rats, in part, through changes in ...

2. joe.bioscientifica.com joe.bioscientifica.com/view/journals/joe/267/1/JOE-25-0184.pdf

Lactobacillus johnsonii N6.2 improves glycemia and reduces ... Here, we report that administration of the probiotic improved glycemic levels and decreased diabetes scores related to injury in the pancreas, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03961854

Lactobacillus Johnsonii in Children and Adolescents With ... 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 ...

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0010507

Lactobacillus johnsonii N6.2 Mitigates the Development of ... It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes.

5. withpower.com withpower.com/trial/phase-3-diabetes-mellitus-type-1-9-2019-4c190

Lactobacillus Johnsonii 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 ...