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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether two BCG vaccinations can improve the immune and metabolic health of children with newly diagnosed Type 1 diabetes. Participants will receive either the BCG vaccine (Bacillus Calmette-Guérin vaccine) or a placebo (a harmless, inactive substance) to compare effects. Children who have had Type 1 diabetes for more than 3 months but less than a year and are currently managing it with insulin might be suitable for this study. The goal is to determine if the BCG vaccine can ease diabetes management and potentially enhance long-term health outcomes. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that the Bacillus Calmette-Guérin (BCG) vaccine is generally safe for people. This old vaccine, primarily used to protect against tuberculosis, has been administered to millions of children worldwide for nearly a century.

While researchers explore new uses for BCG, such as aiding in Type 1 diabetes, its safety in humans remains well-established. Most people tolerate it well, and serious side effects are rare. Common side effects are mild and may include soreness at the injection site or a slight fever.

Since BCG is already approved for tuberculosis, its safety is well-documented. This makes it suitable for testing in new applications, such as this clinical trial for Type 1 diabetes. ^{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 continuous glucose monitoring, the Bacillus Calmette-Guérin (BCG) vaccine offers a novel approach by potentially modulating the immune system. Researchers are excited about BCG because it may alter immune responses in a way that protects insulin-producing cells, which are usually attacked in Type 1 Diabetes. This could lead to a more sustainable and less invasive treatment option, reducing the need for frequent insulin injections and offering a new path for disease management.

What evidence suggests that the BCG vaccine might be an effective treatment for Type 1 diabetes?

This trial will compare the effects of the Bacillus Calmette-Guérin (BCG) vaccine with a saline injection placebo in children with Type 1 diabetes. Research suggests that receiving the BCG vaccine more than once might help manage Type 1 diabetes. Early studies found that BCG could reduce certain harmful white blood cells that cause problems in diabetes. Additionally, a reported drop in HbA1c levels, which measure blood sugar control, occurred after BCG shots in adults with diabetes. While these results are encouraging, strong proof that BCG effectively treats Type 1 diabetes is still lacking. More research is needed to fully understand its effects. ^{1 2 6 7 8}

Who Is on the Research Team?

Denise L Faustman, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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

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

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7139880/

Therapeutic Effects of BCG Vaccination on Type 1 Diabetes ...

There is no robust evidence to support the use of the BCG vaccine for the treatment of T1DM although the HbA1c levels tended to improve.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10141056/

BCG Vaccination and the Risk of Type 1 Diabetes Mellitus

(4) Conclusions: Our study revealed no protective or facilitative effect of prior BCG vaccination in T1D development. Keywords: type 1 diabetes, ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02081326

Study Details | NCT02081326 | Repeat BCG Vaccinations ...

Published Phase I data on repeat BCG vaccinations in long term diabetics showed specific death of some of the disease causing bad white blood cells and also ...

4.

scientificarchives.com

scientificarchives.com/article/bcg-immunotherapy-promising-protection-from-covid-19-and-other-infectious-diseases-in-type-1-diabetics

BCG Immunotherapy: Promising Protection from COVID-19 ...

We found that multi-dose BCG was not only safe but was 92% effective compared to placebo in protecting type 1 diabetics from COVID-19 infection early in the ...

5.

rally.massgeneralbrigham.org

rally.massgeneralbrigham.org/study/pedsbcgtrial

Recruiting Pediatric Subjects with Type 1 Diabetes

In a Phase I adult clinical trial conducted at MGH, two injections of BCG showed a significant decrease in HbA1c without high incidence of hypoglycemia, ...

6.

e-apem.org

e-apem.org/m/journal/view.php?number=1005

Association between the incidence of type 1 diabetes ...

There was a negative correlation between the incidence of tuberculosis and T1DM in children and adolescents aged <15 years at the country level.

7.

journals.plos.org

journals.plos.org/plosone/article?id=10.1371/journal.pone.0276423

Bacille Calmette Guerin (BCG) and prevention of types 1 and ...

Data from Greece also suggests childhood BCG administration may prevent T1D [53]. Therefore for the prevention of diabetes with BCG administered ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0091743521004667

A population-based birth cohort study in Quebec, Canada

The Bacillus Calmette-Guerin (BCG) vaccine could reduce the incidence of type 1 diabetes through non-specific immunomodulation.