Effect of Methyldopa on MHC Class II Antigen Presentation in Type 1 Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by University of Colorado Denver School of Medicine Barbara Davis Center
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Aaron Michels, MD, University of Colorado Denver School of Medicine Barbara Davis Center
ClinicalTrials.gov Identifier:
NCT01883804
First received: June 17, 2013
Last updated: June 19, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention
Diabetes Mellitus, Type 1
Drug: Methyldopa

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Colorado Denver School of Medicine Barbara Davis Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 50
Study Start Date: June 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study group
All participants selected to continue with Methyldopa administration.
Drug: Methyldopa
6 weeks of Methyldopa administration; where the dose will be increased according to safety of efficacy.
Other Name: Aldomet

  Eligibility

Ages Eligible for Study:   18 Years to 46 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Type 1 Diabetes Mellitus
  • 18-46 years of age
  • Residual C-peptide production during screening
  • Positive for at least one islet autoantibody: insulin (if only insulin autoantibody positive, determination must be within two weeks of insulin initiation), GAD-65, IA-2 or ZnT8
  • Positive for at least one gene encoding HLA-DQ8 (DQB*0302)
  • No history of difficult to control hypertension (defined as requiring > 2 anti-hypertensive medications)
  • Agree to intensive management of diabetes with an HgbA1c goal of < 8.0%
  • If female: (a) surgically sterile or (b) postmenopausal or (c) if of reproductive potential, willing to use medically acceptable birth control (e.g. female hormonal contraception, barrier methods or sterilization.) until study completion
  • If male and of reproductive potential, willing to use medically acceptable birth control until study completion, unless the female partner is postmenopausal or surgically sterile

Exclusion Criteria:

  • Unable or unwilling to comply with the requirements of the study protocol
  • No HLA-DQ8 gene (DQB*0302)
  • Difficult to control hypertension (defined as requiring > 2 anti-hypertensive medications)
  • History of postural hypotension or Addison's disease
  • Body Mass Index (BMI) > 30 kg/m2
  • Unstable blood sugar control defined as one or more episodes of severe hypoglycemia (defined as hypoglycemia that required the assistance of another person) within the last 30 days
  • Administration of an experimental agent for T1D at any time or use of an experimental device for T1D within 30 days of screening, unless approved by the study PI
  • History of any organ transplant, including islet cell transplant
  • Active autoimmune or immune deficiency disorder (e.g. sarcoidosis, rheumatoid arthritis)
  • Anticipated pregnancy during the 12 week study period
  • Any social or medical condition that would, in the opinion of the investigator, prevent complete participation in the study or that would pose a significant hazard to the subjects' participation
  • History of active substance abuse within 12 months of screening
  • A psychiatric or medical disorder that would prevent giving informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01883804

Contacts
Contact: Aimon K Alkanani, BA 303-724-6821 aimon.alkanani@ucdenver.edu

Locations
United States, Colorado
Barbara Davis Center for Diabetes, University of Colorado School of Medicine Recruiting
Aurora, Colorado, United States, 80045
Contact: Aimon K Alkanani, BA    303-724-6821    aimon.alkanani@ucdenver.edu   
Principal Investigator: Aaron Michels, MD         
Sponsors and Collaborators
University of Colorado Denver School of Medicine Barbara Davis Center
Juvenile Diabetes Research Foundation
Investigators
Principal Investigator: Aaron Michels, MD Barbara Davis Center for Diabetes, University of Colorado School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Aaron Michels, MD, Effect of Methyldopa on MHC class II Antigen Presentation in Type 1 Diabetes, University of Colorado Denver School of Medicine Barbara Davis Center
ClinicalTrials.gov Identifier: NCT01883804     History of Changes
Other Study ID Numbers: 13-1408
Study First Received: June 17, 2013
Last Updated: June 19, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Colorado Denver School of Medicine Barbara Davis Center:
Diabetes
Diabetes Mellitus
Type 1 Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Methyldopa
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014