search
Back to results

Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

Primary Purpose

Diabetes Mellitus, Type One, Diabetes Mellitus, Type I, Autoimmune Diabetes

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bacillus Calmette-Guérin
Saline injection
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type One focused on measuring Diabetes Mellitus, Type One, Diabetes Mellitus, Type I, Autoimmune Diabetes, Insulin Dependent Diabetes Mellitus 1, IDDM, COVID-19

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • Immunobiology Labs CNY 149

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Bacillus Calmette-Guérin

Saline injection

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change in HbA1c values in juvenile onset type 1 diabetics
A change in the hemoglobin A1c (HbA1c) measurement compared to self

Secondary Outcome Measures

Insulin use in juvenile onset type 1 diabetics (AOO<21 years)
A change in insulin (IDAA1c) use as reported at study visits compared to self in juvenile onset type 1 diabetes.
Endogenous insulin levels in the blood in juvenile onset type 1 diabetics (AOO<21 years)
A change in c-peptide and proinsulin levels (as an analog for endogenous insulin) in the blood compared to self.
Autoimmunity in juvenile onset type 1 diabetes (AOO<21 years)
A change in autoantibodies and autoreactive T cells to monitor the drug mechanism for autoimmune changes.

Full Information

First Posted
March 4, 2014
Last Updated
March 22, 2023
Sponsor
Massachusetts General Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT02081326
Brief Title
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 2015 (undefined)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bacillus Calmette-Guérin
Arm Type
Experimental
Arm Description
2 BCG vaccinations spaced 4 weeks apart during the first year and then 1 vaccination every year for the next 4 years
Arm Title
Saline injection
Arm Type
Placebo Comparator
Arm Description
2 injections spaced 4 weeks apart during the first year, then 1 injection per year for the next 4 years
Intervention Type
Biological
Intervention Name(s)
Bacillus Calmette-Guérin
Intervention Description
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
Intervention Name(s)
Saline injection
Intervention Description
2 injections spaced 4 weeks apart during the first year, then 1 injection per year for the next 4 years
Primary Outcome Measure Information:
Title
Change in HbA1c values in juvenile onset type 1 diabetics
Description
A change in the hemoglobin A1c (HbA1c) measurement compared to self
Time Frame
1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Secondary Outcome Measure Information:
Title
Insulin use in juvenile onset type 1 diabetics (AOO<21 years)
Description
A change in insulin (IDAA1c) use as reported at study visits compared to self in juvenile onset type 1 diabetes.
Time Frame
4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Title
Endogenous insulin levels in the blood in juvenile onset type 1 diabetics (AOO<21 years)
Description
A change in c-peptide and proinsulin levels (as an analog for endogenous insulin) in the blood compared to self.
Time Frame
4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Title
Autoimmunity in juvenile onset type 1 diabetes (AOO<21 years)
Description
A change in autoantibodies and autoreactive T cells to monitor the drug mechanism for autoimmune changes.
Time Frame
4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Other Pre-specified Outcome Measures:
Title
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)
Description
A change in values as compared to self for participants with AOO>21 years of age.
Time Frame
4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Title
COVID-19 and BCG Adaptive Study: Number of Type 1 Diabetics with COVID-19 symptomatic infections
Description
Number of symptomatic COVID-19 infections determined through PCR and antibody testing and symptoms collected through surveys and visits.
Time Frame
15 months beginning January 2020
Title
COVID-19 and BCG Adaptive Study: Impact of COVID-19 (severity, duration of symptoms, absence from work)
Description
A different severity of symptoms, duration of symptoms or absence from work for COVID-19 positive patients in the BCG or Placebo group.
Time Frame
15 months beginning January 2020
Title
COVID-19 and BCG Adaptive Study: Reported Rates of Infectious Diseases
Description
Rate of reported infectious disease adverse events categorized through MedDRA codes between the BCG and Placebo groups.
Time Frame
15 months beginning January 2020

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Denise L Faustman, MD, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Immunobiology Labs CNY 149
City
Charlestown
State/Province
Massachusetts
ZIP/Postal Code
02129
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
36027906
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.
Results Reference
derived
Links:
URL
http://faustmanlab.org/
Description
Faustman Lab Research Website

Learn more about this trial

Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

We'll reach out to this number within 24 hrs