Clinical trial NCT02081326: Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes
Official title: Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Diabetes Mellitus, Type One
Diabetes Mellitus, Type I
Autoimmune Diabetes
Covid19
Keywords: Diabetes Mellitus, Type One
Diabetes Mellitus, Type I
Autoimmune Diabetes
Insulin Dependent Diabetes Mellitus 1
IDDM
COVID-19
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2014-03-07
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Change in HbA1c values in juvenile onset type 1 diabetics
timeFrame: 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Secondary outcomes:
measure: Insulin use in juvenile onset type 1 diabetics (AOO<21 years)
timeFrame: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
measure: Endogenous insulin levels in the blood in juvenile onset type 1 diabetics (AOO<21 years)
timeFrame: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
measure: Autoimmunity in juvenile onset type 1 diabetes (AOO<21 years)
timeFrame: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Other outcomes:
measure: Exploratory: A Change in the above primary and secondary endpoints with Latent Autoimmune diabetes of adults (LADA; [a.k.a. Type 1.5 diabetes]; AOO>21 years)
timeFrame: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
measure: COVID-19 and BCG Adaptive Study: Number of Type 1 Diabetics with COVID-19 symptomatic infections
timeFrame: 15 months beginning January 2020
measure: COVID-19 and BCG Adaptive Study: Impact of COVID-19 (severity, duration of symptoms, absence from work)
timeFrame: 15 months beginning January 2020
measure: COVID-19 and BCG Adaptive Study: Reported Rates of Infectious Diseases
timeFrame: 15 months beginning January 2020
Locations:
city: Charlestown
country: United States
facility: Immunobiology Labs CNY 149
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Denise L Faustman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.