Determination of Dosing and Frequency of BCG Administration to Alter T-Lymphocyte Profiles in Type I Diabetics

Study Overview
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Brief Summary
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Type 1 diabetes is caused by an autoimmune destruction of the insulin producing cells of the pancreas. The investigators have discovered the specific autoimmune cells responsible for destroying the insulin-producing cells in an animal model of type 1 diabetes, and the means of destroying those cells.

Detailed Description
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The investigators are now aiming to use a similar strategy (vaccination with BCG, the vaccine used world-wide to protect against tuberculosis) in human type 1 diabetes to see if the abnormal immune cells can be depleted. This is the first step in trying to cure established type 1 diabetes.

Official Title
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Determination of Dosing and Frequency of BCG Administration Necessary to Alter T-Lymphocyte Profiles in Type I Diabetics

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Biological: BCG
* Biological: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Type 1 diabetic subjects): Type 1 diabetes treated continuously with insulin from time of diagnosis Age 18-55 Anti-GAD positive HIV antibody negative Normal CBC Negative intermediate PPD test performed and read by study staff HCG Negative (females) Exclusion Criteria Type 1 diabetic subjects): History of chronic infectious disease, such as HIV History of tuberculosis, TB risk factors, or history of + PPD, or BCG vaccination Treatment with glucocorticoids (other than intermittent nasal steroids) or disease or condition likely to require steroid therapy Other conditions or treatments associated with increased risk of infections such as patients with 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 Fasting or stimulated (1 mg glucagon stimulation test) c-peptide > 0.2 pmol/mL History of keloid formation HbA1c > 8.0% History or evidence of chronic kidney disease (serum creatinine > 1.5 mg/dL) History of proliferative diabetic retinopathy that has not been treated with laser therapy 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). Inclusion Criteria (Control Non-diabetic Subjects): Age 18-45 Exclusion Criteria (Control Non-diabetic Subjects): History of autoimmune diseases or diabetes History of HIV History of autoimmune disease or type 1 diabetes (use of insulin continuously since diagnosis) in first degree family members

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E<br>BCG vaccination | Biological: BCG<br>* BCG vaccination at 0 and 4 weeks<br>|
| Placebo Comparator: P<br>Saline vaccination | Biological: Saline<br>* Saline vaccination at 0 and 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| concentration of autoreactive t-cells |  | Measured weekly in first 8 weeks, then every other week for weeks 8-12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of TNF, TNF-receptors, other cytokines, and c-peptide levels |  | Weekly for first 8 weeks, then every other week for weeks 8-12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 1 diabetes mellitus, immune modulation, cure, autoimmunity