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Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT02081326
Recruitment Status : Active, not recruiting
First Posted : March 7, 2014
Last Update Posted : August 2, 2021
Sponsor:
Information provided by (Responsible Party):
Denise Louise Faustman, MD, Massachusetts General Hospital

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.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type One Diabetes Mellitus, Type I Autoimmune Diabetes Covid19 Biological: Bacillus Calmette-Guérin Biological: Saline injection Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes
Study Start Date : June 2015
Estimated Primary Completion Date : July 2025
Estimated Study Completion Date : July 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02081326


Locations
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United States, Massachusetts
Immunobiology Labs CNY 149
Charlestown, Massachusetts, United States, 02129
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Denise L Faustman, MD, PhD Massachusetts General Hospital
Additional Information:
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Responsible Party: Denise Louise Faustman, MD, Denise Louise Faustman, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02081326    
Other Study ID Numbers: 2013P002633
First Posted: March 7, 2014    Key Record Dates
Last Update Posted: August 2, 2021
Last Verified: July 2021
Keywords provided by Denise Louise Faustman, MD, Massachusetts General Hospital:
Diabetes Mellitus, Type One
Diabetes Mellitus, Type I
Autoimmune Diabetes
Insulin Dependent Diabetes Mellitus 1
IDDM
COVID-19
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
BCG Vaccine
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs