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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether two BCG vaccinations (Bacillus Calmette-Guérin vaccine) can enhance the immune system and metabolism in children with Type 1 diabetes. The study compares the effects of these vaccinations against a placebo, which has no active effect. Children who have managed Type 1 diabetes with insulin for over two years and use a continuous glucose monitor (CGM) might be suitable candidates. Participants should not have a history of tuberculosis or other chronic infections. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

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.

Is there any evidence suggesting that the BCG vaccine is likely to be safe for humans?

Research has shown that the Bacillus Calmette-Guérin (BCG) vaccine is generally safe for people. In earlier studies, patients who received the BCG vaccine had fewer harmful white blood cells linked to type 1 diabetes. Some adults even showed improved blood sugar levels after receiving several doses of BCG. While these results are encouraging, larger studies continue to explore BCG's full potential for treating type 1 diabetes.

BCG has been widely used to prevent tuberculosis worldwide, supporting its safety in humans. Although the vaccine is considered safe, monitoring for any side effects remains important. Participants in past studies did not report major side effects, suggesting that BCG has a good safety record. ^{1 2 3 4 5}

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

Unlike the standard insulin therapy for Type 1 Diabetes, Bacillus Calmette-Guérin (BCG) is unique because it leverages an old tuberculosis vaccine to potentially modify the immune system. Researchers are excited about BCG because it aims to target the underlying autoimmune process that destroys insulin-producing cells, rather than just managing blood sugar levels. This approach could offer a transformative way to preserve or even restore the body's ability to produce insulin, offering hope for a more effective, long-term solution.

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

Research suggests that receiving the Bacillus Calmette-Guérin (BCG) vaccine more than once might help manage Type 1 diabetes by affecting the immune system. In this trial, participants will receive either two BCG vaccinations or two placebo saline injections, spaced 4 weeks apart. Some studies have shown that BCG vaccinations can help control blood sugar levels by targeting harmful white blood cells. Although strong proof that BCG can treat Type 1 diabetes is lacking, some improvements in HbA1c levels (which measure blood sugar control) have been observed. BCG has also been found safe and effective in protecting people with Type 1 diabetes from infections like COVID-19. While these findings are promising, more research is needed to fully understand its effects on Type 1 diabetes. ^{1 3 4 6 7}

Who Is on the Research Team?

Denise L Faustman, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 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

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.

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+

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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.

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 ...

4.

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 ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1043276018302121

BCG Therapy for Type 1 Diabetes: Restoration of Balanced ...

Repeated BCG vaccinations in long-term diabetics can restore blood sugars to near normal by resetting the immune system and by increasing glucose utilization.

6.

diabetesjournals.org

diabetesjournals.org/diabetes/article/74/Supplement_1/881-P/159629/881-P-BCG-Clinical-Trial-Programs-in-Advanced-Type

881-P: BCG Clinical Trial Programs in Advanced Type 1 ...

In two open-label clinical trials in adults with early onset T1D, HbA1c reduction of 10-15% was observed after multi-dose BCG treatment. A ...

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 ...

Countries that currently administer BCG have a significantly lower T1D incidence rate than those that do not administer the vaccine at birth.