Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

March 22, 2023 updated by: Denise Louise Faustman, MD, Massachusetts General Hospital

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

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

Genders Eligible for Study

All

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

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 (Anticipated)

July 1, 2025

Study Completion (Anticipated)

July 1, 2027

Study Registration Dates

First Submitted

March 4, 2014

First Submitted That Met QC Criteria

March 6, 2014

First Posted (Estimate)

March 7, 2014

Study Record Updates

Last Update Posted (Actual)

March 24, 2023

Last Update Submitted That Met QC Criteria

March 22, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013P002633

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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