Diabetes Mellitus, Tuberculosis
Conditions
Brief summary
The study hypothesis is that type 2 diabetics have abnormal cell-mediated immunity to tuberculosis manifesting as altered cytokine responses by peripheral blood mononuclear cells (PBMCs). This hypothesis will be tested using the live tuberculosis vaccine, Bacille Calmette-Guerin (BCG), in U.S.-born type 2 diabetics and nondiabetics. The investigators will control for potential confounding by age, sex, race, comorbidities, and select medications. Expression of key cytokines will be measured with real-time polymerase chain reaction.
Detailed description
The project has three specific aims: Specific Aim 1: To assess differences between the study groups in cytokine expression before and after BCG vaccination. The investigators will determine within-individual variability in cytokine measurements and describe the kinetics of cytokine response to BCG. Peak response levels, time to peak, and patterns of cytokines expressed will be compared. Specific Aim 2: To evaluate the effect of hyperglycemia on the cytokine response of type 2 diabetics. The investigators will evaluate whether levels of hemoglobin A1C (HbA1C) are associated with degree of cytokine response and test if type 2 diabetics who have good glucose control are different from nondiabetics. Specific Aim 3: To evaluate the effect of testing PBMCs from diabetics outside of their diabetic milieu. Investigators will compare the BCG-specific cytokine responses of PBMCs stimulated in normal medium, PBMCs stimulated in glucose correlating to the person's most recent HbA1C, and whole blood samples.
Interventions
BIOLOGICALBCG
Both arms: diabetics and nondiabetics will receive vaccination in the upper arm with a 0.1-mg intradermal dose of a single strain of BCG (Mycobax, Sanofi-Aventis), which is FDA approved for this indication.
Sponsors
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Type 2 diabetes or healthy individual Able to give consent US-born Age 30-65
Exclusion criteria
\* Immunosuppressive disease * Immunosuppressive medications * Pregnancy * Renal failure * Advanced pulmonary disease * Prior BCG vaccination * Prior TB infection * Type 1 diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antigen-specific Immune Response Measured by Reaction to Tuberculin Skin Test | 5 months | Participants had baseline tuberculin testing (TST), followed by BCG vaccination, and at 5 months after vaccination, study participants had repeat tuberculin skin testing done. |
| Kinetics of Mycobacterial-specific Immune Response After BCG Vaccination | 5 months | Blood was sampled at times 0, 2, 4, 6, 8, 12, 16, and 20 weeks post BCG vaccination and Interferon gamma production was measured as change from pre-vaccination baseline. Timeline of peak IFn-g response was measured for both study groups. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Diabetes Persons with diagnosis of diabetes. Received biological intervention: BCG
BCG: Both arms: diabetics and nondiabetics will receive vaccination in the upper arm with a 0.1-mg intradermal dose of a single strain of BCG (Mycobax, Sanofi-Aventis), which is FDA approved for this indication. | 6 |
| Participants Without Diabetes Persons with no diagnosis of diabetes and negative diabetes screening labs. Received biological intervention: BCG.
BCG: Both arms: diabetics and nondiabetics will receive vaccination in the upper arm with a 0.1-mg intradermal dose of a single strain of BCG (Mycobax, Sanofi-Aventis), which is FDA approved for this indication. | 4 |
| Total | 10 |
Baseline characteristics
| Characteristic | Participants With Diabetes | Participants Without Diabetes | Total |
|---|---|---|---|
| Age, Continuous | 59.5 years | 41.5 years | 54.5 years |
| Hemoglobin A1C | 6.65 % | 5.65 % | 6.1 % |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 |
Outcome results
Primary
Antigen-specific Immune Response Measured by Reaction to Tuberculin Skin Test
Participants had baseline tuberculin testing (TST), followed by BCG vaccination, and at 5 months after vaccination, study participants had repeat tuberculin skin testing done.
Time frame: 5 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants With Diabetes | Antigen-specific Immune Response Measured by Reaction to Tuberculin Skin Test | 0 mm |
| Participants Without Diabetes | Antigen-specific Immune Response Measured by Reaction to Tuberculin Skin Test | 3 mm |
Primary
Kinetics of Mycobacterial-specific Immune Response After BCG Vaccination
Blood was sampled at times 0, 2, 4, 6, 8, 12, 16, and 20 weeks post BCG vaccination and Interferon gamma production was measured as change from pre-vaccination baseline. Timeline of peak IFn-g response was measured for both study groups.
Time frame: 5 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Diabetes | Kinetics of Mycobacterial-specific Immune Response After BCG Vaccination | 8 weeks when peak response was observed | Standard Deviation 1 |
| Participants Without Diabetes | Kinetics of Mycobacterial-specific Immune Response After BCG Vaccination | 8 weeks when peak response was observed | Standard Deviation 1 |