Effect of Methyldopa on MHC Class II Antigen Presentation in Type 1 Diabetes
Type 1 Diabetes is an autoimmune condition in which segments of the immune system cause the destruction of insulin producing cells in the pancreas, leaving individuals with an impaired ability to control blood glucose levels. Currently there is no cure for Type 1 Diabetes and the treatments involve lifelong insulin administration and careful monitoring of blood glucose levels. Long-term complications like cardiovascular disease, nerve damage, and retina damage, may result. Previous studies have shown that improvement in the control of blood glucose can reduce the risks from these long-term complications. Residual insulin production, typically within the first few years following diagnosis, helps to reduce an individual's need to supplement insulin by injection or pump. This effect helps in maintaining the body's ability to regulate blood glucose levels and reducing the needs of external insulin.
Methyldopa, or Aldomet, has been approved by the Food and Drug Administration and is commonly used to treat high blood pressure. This drug has been approved for several decades and has been shown to be safe and effective. This drug has been identified by the researcher to be able to block the communication between two important types of immune cells; which play a critical role in the autoimmune processes of Type 1 Diabetes. The investigators hypothesize that Methyldopa, over a 6 week treatment period, will block this communication and possibly slow down the destruction of insulin producing cells. The investigators hope to assess the appropriate and safe dose to achieve this effect, along with the drug's ability to maintain insulin production and blood glucose control.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open Label Pilot Study of the Effect of Methyldopa on MHC-II Antigen Presentation in Type 1 Diabetes|
- Inhibition of DQ8 Antigen Presentation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Investigators aim to observe inhibition of DQ8 antigen presentation; along with the dose required to achieve this aim. The researchers have devolved an assay to monitor the effect of Methyldopa on the presentation of the DQ8 antigen through the isolation of specific cells found in the blood. Using this assay, the investigators will analyze the ability to block DQ8 antigen presentation as the dose of Methyldopa changes through the course of the study.
- Assessment of C-Peptide Changes [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Investigators aim to observe changes in C-peptide production through the use of Mixed Meal Tolerance Tests. C-peptide is a product of insulin secretion and can help investigators monitor changes in insulin amounts over time. Blood samples will be collected at various time points during the Mixed Meal Tolerance Test, each of which will be analyzed for the amount of c-peptide present.
- Assessment of Insulin Dose and Hemoglobin A1c [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Investigators aim to observe changes in insulin requirements, along with Hemoglobin A1c values, of each participant. Insulin requirements will be reported by each participant during each visit, by way of insulin units being taken or by downloading of insulin pump data. Hemoglobin A1c values will be analyzed during Mixed Meal Tolerance Tests, with the blood already being collected for C-peptide analysis.
- Tolerability of Methyldopa [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]Investigators aim to assess the tolerability of Methyldopa doses required to achieve the primary outcome. This will be assessed through discussions with participants and careful monitoring of any adverse events. Participants will be asked to wear a continuous blood pressure monitor during the 3 days following any changes in the dose of Methyldopa, or any other time point deemed necessary by the study doctor.
|Study Start Date:||June 2013|
|Study Completion Date:||February 2016|
|Primary Completion Date:||February 2016 (Final data collection date for primary outcome measure)|
Experimental: Study group
All participants selected to continue with Methyldopa administration.
6 weeks of Methyldopa administration; where the dose will be increased according to safety of efficacy.
Other Name: Aldomet
Please refer to this study by its ClinicalTrials.gov identifier: NCT01883804
|United States, Colorado|
|Barbara Davis Center for Diabetes, University of Colorado School of Medicine|
|Aurora, Colorado, United States, 80045|
|Principal Investigator:||Aaron Michels, MD||Barbara Davis Center for Diabetes, University of Colorado School of Medicine|