Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

Covid19 Clinical Trial

Official title:

Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02081326
• Other study ID #: 2013P002633
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 2015
• Est. completion date: July 2031

Study information

• Verified date: May 2024
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: July 2031
• Est. primary completion date: July 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Autoimmune Diabetes
• COVID-19
• Covid19
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type I
• Diabetes Mellitus, Type One

Intervention

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

Locations

Country	Name	City	State
United States	Immunobiology Labs CNY 149	Charlestown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)	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
Other	COVID-19 and BCG Adaptive Study: Number of Type 1 Diabetics with COVID-19 symptomatic infections	Number of symptomatic COVID-19 infections determined through PCR and antibody testing and symptoms collected through surveys and visits.	15 months beginning January 2020
Other	COVID-19 and BCG Adaptive Study: Impact of COVID-19 (severity, duration of symptoms, absence from work)	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
Other	COVID-19 and BCG Adaptive Study: Reported Rates of Infectious Diseases	Rate of reported infectious disease adverse events categorized through MedDRA codes between the BCG and Placebo groups.	15 months beginning January 2020
Primary	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	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.	4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Secondary	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.	4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Secondary	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.	4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection

External Links

•   Faustman Lab Research Website