Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

NCT ID: NCT02081326

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2031-07-31

Brief Summary

The purpose of this study is to see if repeat bacillus Calmette-Guérin (BCG) vaccinations can confer a beneficial immune and metabolic effect on Type 1 diabetes. 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 showed a short and small pancreas effect of restored insulin secretion. In this Phase II study, the investigators will attempt to vaccinate more frequently to see if these desirable effects can be more sustained.

Eligible volunteers will either be vaccinated with BCG in a repeat fashion over a period of four years, or receive a placebo treatment. The investigators hypothesize that each BCG vaccination will eliminate more and more of the disease causing white blood cells that could offer relief to the pancreas for increased survival and restoration of insulin secretion from the pancreas.

An additional adaptive trial for COVID-19 is also being conducted on these randomized double blinded type 1 diabetic subjects receiving BCG or placebo injections.

An expanded study arm has been approved for repeat dosing of BCG in adult Type I diabetes.

Conditions

Diabetes Mellitus, Type One; Diabetes Mellitus, Type I; Autoimmune Diabetes; Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Bacillus Calmette-Guérin

2 BCG vaccinations spaced 4 weeks apart during the first year and then 1 vaccination every year for the next 4 years

Group Type: EXPERIMENTAL

Bacillus Calmette-Guérin

Intervention Type: BIOLOGICAL

2 BCG vaccinations spaced 4 weeks apart during the first year and then 1 vaccination every year for the next 4 years

Saline injection

2 injections spaced 4 weeks apart during the first year, then 1 injection per year for the next 4 years

Group Type: PLACEBO_COMPARATOR

Saline injection

Intervention Type: BIOLOGICAL

2 injections spaced 4 weeks apart during the first year, then 1 injection per year for the next 4 years

Interventions

Bacillus Calmette-Guérin

2 BCG vaccinations spaced 4 weeks apart during the first year and then 1 vaccination every year for the next 4 years

Intervention Type: BIOLOGICAL

Saline injection

2 injections spaced 4 weeks apart during the first year, then 1 injection per year for the next 4 years

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Type 1 diabetes treated continuously with insulin from time of diagnosis
• Age 18-65
• HIV antibody negative
• Normal CBC
• HCG negative (females)
• Anti-GAD Positive (except for subjects with c-peptide <10pmol/L)
• Fasting or stimulated c-peptide between 5-200 pmol/L
• Participation in protocol #2001P001379, "Autoimmunity: In Vitro Pathogenesis and Early Detection"

Exclusion Criteria

• History of chronic infectious disease such as HIV or hepatitis
• History of tuberculosis, TB risk factors, positive interferon-gamma release assay (IGRA, also known as the T-SPOT.TB test), or BCG vaccination
• Current treatment with glucocorticoids (other than intermittent nasal or eye steroids), or disease or condition likely to require steroid therapy
• Other conditions or treatments associated with increased risk of infections such as patients with a previous history of severe burns, or treatment with immunosuppressive medications of any type (e.g. imuran, methotrexate, cyclosporine, etanercept, infliximab) for any reason
• Current treatment with aspirin > 160 mg/day or chronic, daily NSAIDs
• Current treatment with antibiotics
• History of keloid formation
• Average HbA1c over the past 5 years (or since diagnosis if duration is less than 5 years) <6.5 or > 8.5%
• History or evidence of chronic kidney disease (serum creatinine > 1.5mg/dL)
• History of proliferative diabetic retinopathy that has not been treated with laser therapy
• History of neuropathy, foot ulcers, amputations, or kidney disease
• Pregnant or not using acceptable birth control
• Living with someone who is immunosuppressed and/or at high risk for infectious diseases (for example HIV+ or taking immunosuppressive medications for any reason)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Denise Louise Faustman, MD

Denise Louise Faustman, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Denise L Faustman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Immunobiology Labs CNY 149

Charlestown, Massachusetts, United States

Countries

United States

References

Faustman DL, Lee A, Hostetter ER, Aristarkhova A, Ng NC, Shpilsky GF, Tran L, Wolfe G, Takahashi H, Dias HF, Braley J, Zheng H, Schoenfeld DA, Kuhtreiber WM. Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes. Cell Rep Med. 2022 Sep 20;3(9):100728. doi: 10.1016/j.xcrm.2022.100728. Epub 2022 Aug 15.

Reference Type: DERIVED

PMID: 36027906 (View on PubMed)

Related Links

http://faustmanlab.org/

Faustman Lab Research Website

Other Identifiers

2013P002633

Identifier Type: -

Identifier Source: org_study_id