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

• ClinicalTrials.gov Identifier: NCT00607230
• Recruitment Status: Completed
• First Posted: February 5, 2008
• Last Update Posted: November 5, 2013
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): David M. Nathan, MD, Massachusetts General Hospital

Tracking Information

• First Submitted Date: January 22, 2008
• First Posted Date: February 5, 2008
• Last Update Posted Date: November 5, 2013
• Study Start Date: November 2007
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 4, 2008): concentration of autoreactive t-cells [ Time Frame: Measured weekly in first 8 weeks, then every other week for weeks 8-12 ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: February 4, 2008): Concentration of TNF, TNF-receptors, other cytokines, and c-peptide levels [ Time Frame: Weekly for first 8 weeks, then every other week for weeks 8-12 ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Type 1 Diabetes Mellitus

Intervention

• Biological: BCG
  BCG vaccination at 0 and 4 weeks
• Biological: Saline
  Saline vaccination at 0 and 4 weeks

Study Arms

• Experimental: E
  BCG vaccination
  Intervention: Biological: BCG
• Placebo Comparator: P
  Saline vaccination
  Intervention: Biological: Saline

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 4, 2008): 25
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: February 2011
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00607230
• Other Study ID Numbers: 2007p-001347
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: David M. Nathan, MD, Massachusetts General Hospital
• Original Responsible Party: David M. Nathan, MD, Massachusetts General Hospital
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: David M Nathan, MD; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: November 2013