Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

Mass General Brigham

Status and phase

Active, not recruiting

Phase 2

Conditions

Diabetes Mellitus, Type One

Diabetes Mellitus, Type I

Covid19

Autoimmune Diabetes

Treatments

Biological: Saline injection

Biological: Bacillus Calmette-Guérin

Study type

Interventional

Funder types

Other

Identifiers

NCT02081326

2013P002633

Details and patient eligibility

About

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.

Enrollment

150 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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)