Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Denise Louise Faustman, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT02081326
First received: March 4, 2014
Last updated: June 8, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type One
Diabetes Mellitus, Type I
Autoimmune Diabetes
Biological: Bacillus Calmette-Guérin
Biological: Saline injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Improvement in HbA1c [ Time Frame: 1, 2, 3, 4, and 5 years after initial BCG/placebo injection ] [ Designated as safety issue: No ]
    An improvement in the hemoglobin A1c (HbA1c) measurement compared to self


Secondary Outcome Measures:
  • Change in Immune Response [ Time Frame: 2 and 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection ] [ Designated as safety issue: No ]
    Beneficial immune changes of autoimmune reversal that may also lead to a change in insulin


Other Outcome Measures:
  • Stabilization in Urinary C-peptide [ Time Frame: 1, 2, 3, 4, and 5 years after initial BCG/placebo injection ] [ Designated as safety issue: No ]
    Stabilization or improvement in urinary c-peptide of BCG treated group as compared to placebo group or self

  • Stabilization of Stimulated C-peptide [ Time Frame: 1, 2, 3, 4, and 5 years after initial BCG/placebo injection ] [ Designated as safety issue: No ]
    Improvement or stabilization in stimulated C-peptide (self insulin) as measured by a mixed meal tolerance test (MMTT) when compared to self or placebo treated group


Estimated Enrollment: 150
Study Start Date: June 2015
Estimated Study Completion Date: July 2023
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02081326

Contacts
Contact: Denise L Faustman, MD, PhD 617-726-4084 diabetestrial@partners.org

Locations
United States, Massachusetts
Immunobiology Labs CNY 149 Recruiting
Charlestown, Massachusetts, United States, 02129
Contact: Denise L Faustman, MD, PhD    617-726-4084    diabetestrial@partners.org   
Principal Investigator: Denise L. Faustman, MD, PhD         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Denise L Faustman, MD, PhD Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Denise Louise Faustman, MD, Denise Louise Faustman, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02081326     History of Changes
Other Study ID Numbers: 2013P002633
Study First Received: March 4, 2014
Last Updated: June 8, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Diabetes Mellitus, Type One
Diabetes Mellitus, Type I
Autoimmune Diabetes
Insulin Dependent Diabetes Mellitus 1
IDDM

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
BCG Vaccine
Adjuvants, Immunologic
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 27, 2015