Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

April 8, 2026 updated by: Denise Louise Faustman, MD, Massachusetts General Hospital

This Phase II RCT using multi-dose Bacillus Calmette-Guérin (BCG) in adults with juvenile or childhood onset diabetes is based on prior clinical trials showing that even with advanced disease and little of no remaining pancreas activity, HbA1c can be lowered. Prior clinical trials with this highly desired outcome include Phase 1B and two open label clinical trials (2007p001347; IND 10435). The mechanism of restored glucose control was independent of the pancreas; BCG restored regulated sugar transport (aerobic glycolysis) throughout the lymphoid system for normoglycemia.

In the planning for this 10 year long Phase II clinical trial, with first 5 year unblinding, Dr David Schoenfeld, Chief of Biostatics at MGH in SAP 0.0 modeled that 51 long term adult diabetic subjects randomized 2:1 with BCG vaccines over 5 years, would have high probably of repeating the past success in achieving lowered HbA1c in the Phase 1B clinical trial (2012P002243). This Primary outcome and the Primary study population in adults but with juvenile onset disease was the original and continuous outcome for this Phase II clinical trial (IND16434).

In addition to routine protocol changes throughout this study, additional studies were added. These same subjects were both studied in a concurrent Phase II and Phase III infectious disease adaptive clinical trial confirming that BCG provided protection from all infectious diseases and COVID-19 in this vulnerable population, confirming past work of many investigators in Europe (2020P001462). As an early added Exploratory outcome, the trial enrollment numbers were expanded to include latent autoimmune diabetes subjects (LADA), an autoimmune type of diabetes with adult onset. As was reported prior to this trial start, LADA adults lack the necessary lymphoid aerobic defects restored by BCG in the lymphocytes of juvenile onset subjects but have the very slow decay of the pancreas. The slow decay of the pancreas tested the Exploratory outcome of the ability of BCG to induce of T regulatory cells (Treg cells) to possibly halt continued loss of insulin in the pancreas i.e. the autoimmune disease attack of the insulin secreting insulin secreting islets and impact of C-peptide secondary outcomes. Throughout all protocols the study of proteomics was contemplated from collected samples at the end of the study. Proteomics revealed important protein changes related to Alzheimer's complications. The protocol was modified to also generate confirmatory data using FDA approved Alzheimer's diagnostics (IND16434; IND 181620). Additional changes to IND 16434 at the suggestion of the FDA included adding an additional study of PET FDG uptake scan to look for the organ systems wherein BCG induced improved sugar uptake. IND 16434 also allowed a limited number of subjects to have Expanded access. IND 16434 at the 5-year mark will be unblinded for the first data analysis of the 10-year study; placebo subjects can continue with or without the BCG and previous treated BCG can continue as placebo subjects during this "cross over study".

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Charlestown, Massachusetts, United States, 02129
        • Immunobiology Labs CNY 149

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Biological: 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
Placebo Comparator: Saline injection
2 injections spaced 4 weeks apart during the first year, then 1 injection per year for the next 4 years
Biological: Saline injection
2 injections spaced 4 weeks apart during the first year, then 1 injection per year for the next 4 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in HbA1c values in juvenile onset type 1 diabetics
Time Frame: 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
A change in the hemoglobin A1c (HbA1c) measurement compared to self
1, 2, 3, 4, and 5 years after initial BCG/placebo injection

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin use in juvenile onset type 1 diabetics (AOO<21 years)
Time Frame: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
A change in insulin (IDAA1c) use as reported at study visits compared to self in juvenile onset type 1 diabetes.
4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Endogenous insulin levels in the blood in juvenile onset type 1 diabetics (AOO<21 years)
Time Frame: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
A change in c-peptide and proinsulin levels (as an analog for endogenous insulin) in the blood compared to self.
4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Autoimmunity in juvenile onset type 1 diabetes (AOO<21 years)
Time Frame: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
A change in autoantibodies and autoreactive T cells to monitor the drug mechanism for autoimmune changes.
4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
A change in values as compared to self for participants with AOO>21 years of age.
4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
COVID-19 and BCG Adaptive Study: Number of Type 1 Diabetics with COVID-19 symptomatic infections
Time Frame: 15 months beginning January 2020
Number of symptomatic COVID-19 infections determined through PCR and antibody testing and symptoms collected through surveys and visits.
15 months beginning January 2020
COVID-19 and BCG Adaptive Study: Impact of COVID-19 (severity, duration of symptoms, absence from work)
Time Frame: 15 months beginning January 2020
A different severity of symptoms, duration of symptoms or absence from work for COVID-19 positive patients in the BCG or Placebo group.
15 months beginning January 2020
COVID-19 and BCG Adaptive Study: Reported Rates of Infectious Diseases
Time Frame: 15 months beginning January 2020
Rate of reported infectious disease adverse events categorized through MedDRA codes between the BCG and Placebo groups.
15 months beginning January 2020

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Principal Investigator: Denise L Faustman, MD, PhD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Estimated)

July 1, 2029

Study Completion (Estimated)

July 1, 2031

Study Registration Dates

First Submitted

March 4, 2014

First Submitted That Met QC Criteria

March 6, 2014

First Posted (Estimated)

March 7, 2014

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 8, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013P002633

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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