BCG Vaccinations for Type 1 Diabetes

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: Glucocorticoids, Immunosuppressives, NSAIDs, others

Disqualifiers: Chronic infections, Tuberculosis, Hepatitis, 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

150 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 exclude those on certain treatments like high-dose steroids, chronic antibiotics that interfere with BCG, and oral type 2 diabetes drugs. It's best to discuss your specific medications with the trial team.

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

Research shows that the BCG vaccine can modulate the immune system, potentially slowing the progression of type 1 diabetes by reducing harmful immune cells and increasing beneficial ones. Clinical trials have shown promise in restoring some insulin production in people with long-standing type 1 diabetes. ^{1 2 3 4 5}

Is the BCG vaccine generally safe for humans?

The BCG vaccine is generally safe for humans, with mild and benign local side effects being the most common. Serious side effects are rare. ^{1 3 4 6 7}

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

The BCG vaccine is unique because it modulates the immune system to reduce harmful immune cells and increase beneficial ones, potentially slowing the progression of type 1 diabetes. Unlike standard treatments that focus on managing blood sugar, BCG aims to address the underlying autoimmune process. ^{1 2 3 4 8}

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 on pediatric Type 1 diabetes.

Research Team

Denise L Faustman, MD, PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for kids aged 12-17 with Type 1 diabetes, who can manage multiple daily insulin injections and use a continuous glucose monitor (CGM). They must have certain diabetes-related antibodies, detectable C-peptide levels, and no history of severe diabetic complications or other serious health conditions. Pregnant teens or those at risk of pregnancy without contraception are excluded.

Inclusion Criteria

I have antibodies linked to diabetes.

I am willing and able to take 3 insulin injections daily with meals during the trial.

I have been a Type 1 diabetic for over 2 years and am on insulin.

Exclusion Criteria

Any condition, which, in the opinion of the Investigator, might jeopardize the Subject's safety or compliance with the protocol

My blood pressure is higher than what's typical for my age and sex.

I haven't taken diabetes medication not listed in the criteria in the last 90 days.

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

Trial Overview The study tests whether repeated BCG vaccinations can improve immune response and blood sugar control in young people with Type 1 diabetes. Participants will either receive the BCG vaccine or a saline injection as a placebo to compare effects.

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+

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

Findings from Research

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]

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]

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]

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 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 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]

A study of 95 children under 3 years old in Thailand revealed that regional lymphadenitis was the most common adverse effect of BCG vaccination, with 92% of cases presenting this condition, often requiring medical intervention.

The research indicated that BCG osteitis occurred in immunocompetent children, highlighting the potential virulence of the BCG vaccine in neonates and suggesting a need for improved surveillance and reporting systems for vaccine-related adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features and outcomes of Bacille Calmette-Guérin (BCG)-induced diseases following neonatal BCG Tokyo-172 strain immunization. Rermruay, R., Rungmaitree, S., Chatpornvorarux, S., et al.[2022]

In animal models, Freund's complete adjuvant (CFA) and BCG vaccine significantly reduced the incidence of type 1 diabetes, suggesting a potential for these treatments to alter the autoimmune response.

In a preliminary trial with 17 newly diagnosed type 1 diabetic patients, 65% experienced clinical remission after receiving BCG, with no reported side effects, indicating a promising safety profile and efficacy that warrants further investigation in a double-blind trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of adjuvant therapy on development of diabetes in mouse and man. Shehadeh, N., Calcinaro, F., Bradley, BJ., et al.[2019]

References

1. 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]

2. 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]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical features and outcomes of Bacille Calmette-Guérin (BCG)-induced diseases following neonatal BCG Tokyo-172 strain immunization. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Effect of adjuvant therapy on development of diabetes in mouse and man. [2019]