BCG Vaccinations for Type 1 Diabetes in Children

Overseen By Denise L Faustman, MD, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Insulin

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

Disqualifiers: Tuberculosis, Lupus, Type 2 diabetes, others

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

Approved in 7 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot be on certain medications like high-dose aspirin, chronic antibiotics, or glucocorticoids. It also states that you should not start or change medications that affect glucose metabolism within 14 days before the trial.

What data supports the effectiveness of the BCG vaccine treatment for type 1 diabetes in children?

Research suggests that the BCG vaccine may help in type 1 diabetes by modulating the immune system, potentially slowing disease progression and improving insulin production. Some studies show that BCG can reduce harmful immune cells and increase beneficial ones, which might help manage type 1 diabetes. ^{1 2 3 4 5}

Is the BCG vaccine safe for use in humans?

The BCG vaccine, originally developed for tuberculosis prevention, has been used safely in humans for many years. Clinical trials have shown it to be generally safe, with studies indicating its potential use in treating type 1 diabetes and other immune conditions without significant safety concerns. ^{1 3 4 5 6}

How does the BCG vaccine treatment differ from other treatments for type 1 diabetes in children?

The BCG vaccine is unique because it modulates the immune system to potentially slow down the progression of type 1 diabetes, unlike standard treatments that primarily focus on managing blood sugar levels. It involves administering a vaccine that is traditionally used for tuberculosis, which may have effects on the immune system that could delay the onset of type 1 diabetes. ^{1 2 4 5 6}

What is the purpose of this trial?

The purpose of this study is to investigate if repeat bacillus Calmette-Guérin (BCG) vaccinations can confer a beneficial immune and metabolic effect in new onset pediatric Type 1 diabetes.

Research Team

Denise L Faustman, MD, PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Children aged 8 to less than 18 with new onset Type 1 diabetes, diagnosed between 3-12 months ago. They must not have HIV, TB, or be pregnant and should have normal blood tests except for mild creatinine elevation. Participants need to be able to monitor their glucose levels and commit to the study protocol.

Inclusion Criteria

I have given my consent, and if applicable, my child has agreed to participate in the trial.

I was diagnosed with Type 1 diabetes between 3 and 12 months ago.

You have been diagnosed with type 1 diabetes before joining the study, as confirmed by specific blood sugar levels.

Exclusion Criteria

You have a history of repeatedly going to the hospital for not following medical advice and getting a serious condition called ketoacidosis.

You were not born in the US or in a country where BCG vaccinations are required.

I plan to start or change a medication soon that could affect my blood sugar levels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 BCG vaccinations or placebo injections spaced 4 weeks apart

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Annual visits (in-person)

Treatment Details

Interventions

• Bacillus Calmette-Guérin
• Saline Injection

Trial Overview The trial is testing whether repeated vaccinations with Bacillus Calmette-Guérin (BCG) can positively affect the immune system and metabolism in children who recently developed Type 1 diabetes.

Participant Groups

Group I: Bacillus Calmette-Guérin Experimental Treatment 1 Intervention

2 BCG vaccinations spaced 4 weeks apart at the beginning of the trial

Group II: Saline Injection Placebo Group 1 Intervention

2 placebo injections spaced 4 weeks apart at the beginning of the trial

Bacillus Calmette-Guérin is already approved in European Union, Canada, Japan, China, India, Brazil, United States for the following indications:

Approved in European Union as BCG Vaccine for:

• Tuberculosis prevention
• Bladder cancer treatment

Approved in Canada as BCG Vaccine for:

• Tuberculosis prevention in high-risk groups
• Bladder cancer treatment

Approved in Japan as BCG Vaccine for:

• Tuberculosis prevention
• Bladder cancer treatment

Approved in China as BCG Vaccine for:

• Tuberculosis prevention
• Bladder cancer treatment

Approved in India as BCG Vaccine for:

• Tuberculosis prevention
• Bladder cancer treatment

Approved in Brazil as BCG Vaccine for:

• Tuberculosis prevention
• Bladder cancer treatment

Approved in United States as BCG Vaccine for:

• Bladder cancer treatment

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Findings from Research

A systematic review of four randomized controlled trials involving 198 subjects found that the BCG vaccine did not significantly improve glycemic control in type 1 diabetes, as indicated by unchanged HbA1c and fasting C-peptide levels compared to placebo.

While there was a slight tendency for HbA1c levels to improve with the BCG vaccine, the evidence is not strong enough to recommend its use for treating type 1 diabetes, highlighting the need for further research on its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Effects of BCG Vaccination on Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Chang, YC., Lin, CJ., Hsiao, YH., et al.[2022]

In a study involving 94 children with new-onset type 1 diabetes, the BCG vaccine did not significantly increase the remission rate or preserve beta-cell function compared to a placebo.

Both groups showed a decline in C-peptide levels, insulin requirements, and HbA1c levels over the 2-year period, indicating that BCG vaccination does not provide additional benefits in managing type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes. A randomized clinical study. Allen, HF., Klingensmith, GJ., Jensen, P., et al.[2022]

The BCG vaccine, originally developed for tuberculosis, shows promise in treating type 1 diabetes and other autoimmune diseases by selectively eliminating harmful T cells and promoting beneficial regulatory T cells (Tregs).

In a Phase I trial involving adults with advanced type 1 diabetes, BCG vaccination led to a temporary restoration of insulin production and a reduction in autoreactive T cells, highlighting its potential as a therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TNF, TNF inducers, and TNFR2 agonists: A new path to type 1 diabetes treatment. Faustman, DL.[2018]

In a study of 387,704 individuals in Quebec, BCG vaccination in early life did not show a protective effect against the development of type 1 diabetes, with a similar incidence in vaccinated and unvaccinated groups.

The analysis found no significant association between the age at which individuals received the BCG vaccine and the risk of developing type 1 diabetes, indicating that BCG vaccination is unlikely to prevent this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between Bacillus Calmette-Guerin vaccination and type 1 diabetes in adolescence: A population-based birth cohort study in Quebec, Canada. Corsenac, P., Parent, MÉ., Benedetti, A., et al.[2022]

A single dose of the BCG vaccine administered at age 9 may delay the onset of type 1 diabetes (T1D) by approximately 2.5 years, based on a study of 196 patients.

The study found that BCG vaccinated individuals were diagnosed with T1D at a later age compared to non-vaccinated individuals, suggesting that multiple doses of BCG could further prolong the disease-free interval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Pediatric BCG Vaccine in Type 1 Diabetes Onset. Doupis, J., Kolokathis, K., Markopoulou, E., et al.[2021]

BCG vaccination in early life is linked to a reduced risk of developing type 1 diabetes after age 30 and type 2 diabetes in adulthood, based on a study of 396,118 individuals in Quebec.

No significant association was found between BCG vaccination and latent autoimmune diabetes (LADA), suggesting that the protective effects of BCG may vary by diabetes phenotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early life Bacillus Calmette-Guerin vaccination and incidence of type 1, type 2, and latent autoimmune diabetes in adulthood. Corsenac, P., Parent, MÉ., Mansaray, H., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Therapeutic Effects of BCG Vaccination on Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2022]

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

Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes. A randomized clinical study. [2022]

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

TNF, TNF inducers, and TNFR2 agonists: A new path to type 1 diabetes treatment. [2018]

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

Association between Bacillus Calmette-Guerin vaccination and type 1 diabetes in adolescence: A population-based birth cohort study in Quebec, Canada. [2022]

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

The Role of Pediatric BCG Vaccine in Type 1 Diabetes Onset. [2021]

6. France pubmed.ncbi.nlm.nih.gov

Early life Bacillus Calmette-Guerin vaccination and incidence of type 1, type 2, and latent autoimmune diabetes in adulthood. [2022]