Probiotics for Type 1 Diabetes

Overseen By Susanne Cabrera, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must not be taking: Probiotics, Antibiotics, Glucocorticoids, others

Disqualifiers: Pregnancy, Lactation, Celiac, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the probiotic Lactobacillus plantarum 299v can reduce inflammation and maintain some pancreatic function in people newly diagnosed with Type 1 diabetes. The hypothesis is that changes in gut bacteria might improve the condition after diagnosis. Participants will take either the probiotic or a placebo (a harmless pill with no active ingredients) daily for six months. This trial suits individuals diagnosed with Type 1 diabetes less than 100 days ago, who have not used probiotics or antibiotics in the past month, and do not have a dairy allergy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop using probiotics, antibiotics, non-insulin diabetes medications, glucocorticoids, and other immunosuppressive agents at least 30 days before screening. If you are taking medications that affect glucose tolerance, you may also need to stop those.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Lactiplantibacillus plantarum 299v, a type of probiotic, is safe to use. The FDA considers it Generally Recognized as Safe (GRAS), indicating its wide acceptance as safe in food and supplements.

Although used in many foods and supplements, probiotics can sometimes cause minor side effects like gas or bloating, especially at the start of use. However, serious side effects are rare.

In studies involving this probiotic, many people have used it without serious problems. While some might experience mild digestive issues, it generally appears to be well-tolerated. ^{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 and blood sugar monitoring, Lactiplantibacillus plantarum 299v is a probiotic that aims to work differently by potentially influencing gut health and the immune system. Researchers are excited about this treatment because it introduces a new active ingredient, Lactiplantibacillus plantarum, which may help regulate the immune response linked to Type 1 Diabetes. This could offer a novel approach to managing the disease, potentially reducing dependence on insulin and improving quality of life for patients.

What evidence suggests that Lactiplantibacillus plantarum 299v might be an effective treatment for Type 1 diabetes?

Research has shown that Lactiplantibacillus plantarum 299v, a probiotic studied in this trial, might help manage Type 1 diabetes. Studies have found that it can ease stress on beta cells, which are crucial for insulin production. This probiotic also boosts the body's antioxidant defenses, potentially protecting these cells. In animal studies, Lp299v prevented Type 1 diabetes under certain conditions. These findings suggest that Lp299v could reduce inflammation and support insulin-producing cells in people with Type 1 diabetes. Participants in this trial will receive either Lp299v or a placebo to evaluate its effectiveness. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals aged 3-45 recently diagnosed with Type 1 Diabetes, who have at least one diabetes autoantibody. They must not have used probiotics or antibiotics in the past month and should not be on non-insulin hyperglycemia therapies. Women of childbearing age must use birth control during the study.

Inclusion Criteria

I can have children and agree to use birth control during the study.

Your peak C-peptide level during a specific test is higher than 0.2 nmol/L.

You have been diagnosed with Type 1 diabetes within the last 100 days according to ADA guidelines.

Exclusion Criteria

Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results

I have taken antibiotics in the last month.

I have a stable thyroid condition but no other chronic autoimmune diseases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily treatment with either Lp299v supplementation or placebo for 6 months

6 months

Monthly visits (in-person) for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term monitoring

Participants are monitored for changes in systemic inflammation and beta cell function over 5 years

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Lactiplantibacillus plantarum 299v
• Placebo

Trial Overview The study tests if Lactiplantibacillus plantarum (a probiotic) can reduce inflammation and help maintain insulin-producing cell function in new Type 1 Diabetes patients by altering gut bacteria.

How Is the Trial Designed?

Group I: Treatment Group Experimental Treatment 1 Intervention

Subjects will be randomized to the treatment or placebo group. The treatment is a capsule taken by mouth once a day for 6 months.

Group II: Placebo Group Placebo Group 1 Intervention

Subjects will be randomized to the treatment or placebo group. The placebo is a capsule taken by mouth once a day for 6 months.

Lactiplantibacillus plantarum 299v is already approved in European Union, United States for the following indications:

Approved in European Union as Lactiplantibacillus plantarum 299v for:

• Irritable Bowel Syndrome (IBS)
• Inflammatory Bowel Disease (IBD)
• Iron absorption

Approved in United States as Lactiplantibacillus plantarum 299v for:

• Dietary supplement for gastrointestinal health
• Iron absorption

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

The probiotic Lactobacillus plantarum Dad-13, taken daily for 11 weeks by women with type 2 diabetes, led to a significant decrease in HbA1c levels, indicating potential benefits for blood sugar control, although it did not significantly outperform the placebo group.

Supplementation with L. plantarum Dad-13 increased the number of this probiotic in the gut microbiome, but did not significantly alter other gut bacteria populations or levels of short-chain fatty acids, suggesting that while it can colonize the gut, its broader metabolic effects may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Probiotic Lactobacillus plantarum Dad-13 on Metabolic Profiles and Gut Microbiota in Type 2 Diabetic Women: A Randomized Double-Blind Controlled Trial. Rustanti, N., Murdiati, A., Juffrie, M., et al.[2022]

The study will involve 96 children aged 8 to 17 with newly diagnosed type 1 diabetes, testing the effects of probiotics Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function over 6 months.

The primary outcome will measure changes in C-peptide levels after meals, which is crucial for assessing insulin production and beta-cell function in these children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: protocol of a randomised controlled trial. Groele, L., Szajewska, H., Szypowska, A.[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 spontaneously diabetic DRlyp/lyp rats, a gluten-free hydrolyzed casein diet (HCD) significantly delayed the onset of diabetes compared to a normal cereal diet, with the addition of Lactiplantibacillus plantarum 299 v (Lp299v) further extending this delay.

The combination of HCD and Lp299v not only delayed diabetes but also enhanced the gut microbiota and increased levels of beneficial metabolites like propionate and butyrate, which were linked to improved antioxidative defense mechanisms in pancreatic β-cells, suggesting a potential new approach to diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactiplantibacillus plantarum 299v supplementation modulates &#946;-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats. Sargin, P., Roethle, MF., Jia, S., et al.[2023]

Levilactobacillus brevis RAMULAB49, a probiotic strain isolated from fermented pineapple, shows promising antidiabetic properties by significantly inhibiting key enzymes like α-amylase and α-glucosidase, which are involved in carbohydrate digestion.

The strain exhibits beneficial characteristics such as strong antioxidant activity, antimicrobial properties, and good adhesion capabilities, suggesting its potential for therapeutic applications in diabetes management, although further in vivo studies are needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of carbohydrate hydrolyzing enzymes by a potential probiotic Levilactobacillus brevis RAMULAB49 isolated from fermented Ananas comosus. Martiz, RM., Kumari V B, C., Huligere, SS., et al.[2023]

Lactiplantibacillus plantarum Y15, a probiotic isolated from traditional Chinese dairy, showed significant antidiabetic effects in vivo by improving biochemical markers related to type 2 diabetes and reducing inflammation.

The probiotic altered gut microbiota composition, decreasing harmful LPS-producing bacteria and increasing beneficial short-chain fatty acids (SCFAs)-producing bacteria, which contributed to lower levels of pro-inflammatory cytokines and improved insulin signaling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactiplantibacillus plantarum Y15 alleviate type 2 diabetes in mice via modulating gut microbiota and regulating NF-κB and insulin signaling pathway. Liu, Y., Zheng, S., Cui, J., et al.[2022]

The genetically engineered probiotic Lactobacillus plantarum-pMG36e-GLP-1 effectively alleviated symptoms of type 2 diabetes in mice, improving insulin secretion and promoting pancreatic health.

This novel probiotic not only regulated gut microbiota and reduced inflammation but also demonstrated potential for long-term diabetes management, making it a promising therapeutic option for type 2 diabetes treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement effect of a next-generation probiotic L. plantarum-pMG36e-GLP-1 on type 2 diabetes mellitus via the gut-pancreas-liver axis. Hu, H., Luo, J., Liu, Y., et al.[2023]

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]

Lactiplantibacillus plantarum MG4296 and Lacticaseibacillus paracasei MG5012 were effective in reducing insulin resistance and improving metabolic changes in both lab-grown liver cells and mice fed a high-fat diet, indicating their potential as probiotics for diabetes management.

In vivo studies showed that these probiotics significantly improved body weight, glucose tolerance, and various metabolic markers, while also enhancing key signaling pathways related to insulin action, suggesting a mechanism for their beneficial effects on type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactiplantibacillus plantarum MG4296 and Lacticaseibacillus paracasei MG5012 Ameliorates Insulin Resistance in Palmitic Acid-Induced HepG2 Cells and High Fat Diet-Induced Mice. Won, G., Choi, SI., Kang, CH., et al.[2021]

Lactobacillus plantarum HAC01 significantly reduced blood glucose and HbA1c levels in mice with type 2 diabetes, improving glucose tolerance and insulin resistance over a 10-week treatment period.

The probiotic enhanced liver glucose metabolism by increasing AMPK and Akt phosphorylation, protecting insulin-producing β-cells, and restoring beneficial gut microbiota, suggesting it could be an effective therapy for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus plantarum HAC01 ameliorates type 2 diabetes in high-fat diet and streptozotocin-induced diabetic mice in association with modulating the gut microbiota. [2022]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36261888/

Lactiplantibacillus plantarum 299v supplementation ... - PubMed Lactiplantibacillus plantarum 299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9586621/

Lactiplantibacillus plantarum 299v supplementation ... Lactiplantibacillus plantarum 299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0165247825000033

The benefits of Lactiplantibacillus plantarum Lactobacillus plantarum HAC01 ameliorates type 2 diabetes in high-fat diet and streptozotocin-induced diabetic mice in association with modulating the gut ...

4. link.springer.com link.springer.com/article/10.1007/s12602-024-10287-3

The Health Benefits of Probiotic Lactiplantibacillus plantarum Probiotic supplementation with L. plantarum could potentially improve outcomes in patients with irritable bowel syndrome (IBS) symptoms. Fewer ...

5. fda.gov fda.gov/files/food/published/GRAS-Notice-000685---Lactobacillus-plantarum-strain-299v.pdf

GRAS Notice 685, Lactobacillus plantarum strain 299v The results shown in. Table 1 are based upon seven days' growth, and identify strain 299v as L. plantarum. GRAS Determination for. 5. JHEIMBACH ...

6. webmd.com webmd.com/vitamins/ai/ingredientmono-1672/lactiplantibacillus-plantarum

Lactiplantibacillus Plantarum - Uses, Side Effects, and More Lactiplantibacillus plantarum (L. plantarum) is a type of probiotic ("good" bacteria) found in the mouth and gut. It's also found in fermented foods.