Clinical trial NCT00607230: Determination of Dosing and Frequency of BCG Administration to Alter T-Lymphocyte Profiles in Type I Diabetics
Official title: Determination of Dosing and Frequency of BCG Administration Necessary to Alter T-Lymphocyte Profiles in Type I Diabetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Keywords: type 1 diabetes mellitus
immune modulation
cure
autoimmunity
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2008-02-05
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: concentration of autoreactive t-cells
timeFrame: Measured weekly in first 8 weeks, then every other week for weeks 8-12
Secondary outcomes:
measure: Concentration of TNF, TNF-receptors, other cytokines, and c-peptide levels
timeFrame: Weekly for first 8 weeks, then every other week for weeks 8-12
Other outcomes:
Locations:
city: Boston
country: United States
facility: Diabetes Research Center at Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: David M Nathan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Faustman DL, Wang L, Okubo Y, Burger D, Ban L, Man G, Zheng H, Schoenfeld D, Pompei R, Avruch J, Nathan DM. Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes. PLoS One. 2012;7(8):e41756. doi: 10.1371/journal.pone.0041756. Epub 2012 Aug 8.