Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

NCT02081326 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2013P002633
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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".

Conditions

Autoimmune Diabetes; Diabetes Mellitus, Type One; Diabetes Mellitus, Type I; Covid19

Keywords

Diabetes Mellitus, Type One; Diabetes Mellitus, Type I; Autoimmune Diabetes; Insulin Dependent Diabetes Mellitus 1; IDDM; COVID-19

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c values in juvenile onset type 1 diabetics

  A change in the hemoglobin A1c (HbA1c) measurement compared to self

  1, 2, 3, 4, and 5 years after initial BCG/placebo injection

Secondary Outcomes (3)

• Insulin use in juvenile onset type 1 diabetics (AOO<21 years)

  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)

  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)

  4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection

Other Outcomes (4)

• 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)

  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

  15 months beginning January 2020

• COVID-19 and BCG Adaptive Study: Impact of COVID-19 (severity, duration of symptoms, absence from work)

  15 months beginning January 2020

Study Arms (2)

Bacillus Calmette-Guérin

EXPERIMENTAL

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

Saline injection

PLACEBO COMPARATOR

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

Biological: Saline injection

Interventions

Bacillus Calmette-Guérin BIOLOGICAL

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

Bacillus Calmette-Guérin

Saline injection BIOLOGICAL

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

Saline injection

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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"

You may not qualify if:

• 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)

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Immunobiology Labs CNY 149

Charlestown, Massachusetts, 02129, United States

Location

Related Publications (1)

• 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.

  PMID: 36027906 DERIVED

Related Links

• Faustman Lab Research Website

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 1; COVID-19

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Denise L Faustman, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Denise Louise Faustman, MD, PhD

Study Record Dates

• First Submitted: March 4, 2014
• First Posted: March 7, 2014
• Study Start: June 1, 2015
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2031
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (1)