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NCT Number: NCT01883804

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.

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Key information

Conditions

Diabetes Mellitus, Type 1 Autoimmune Diseases Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–46 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Barbara Davis Center for Diabetes, University of Colorado School of Medicine

Aurora, Colorado, 80045, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Methyldopa

Drug

6 weeks of Methyldopa administration; where the dose will be increased according to safety of efficacy.

Other names: Aldomet

Primary outcomes

  1. The Change From Baseline of DQ8 Antigen Presentation by Peripheral Blood Mononuclear Cells After 6 Weeks of Methyldopa Treatment.

    Time frame: 6 Weeks (Baseline and week 6)

    Cryopreserved primary peripheral blood mononuclear cells were used as antigen presenting cells to stimulate engineered T-cells (T-cell receptor transductant) responding to a specific peptide presented by HLA-DQ8. Secreted IL-2 from the engineered T-cell was measured by a highly sensitive ELISA. This was done for both an α-gliadin/DQ8 responding T-cell and a separate insulin/DQ8 responding T-cell.

Secondary outcomes

  1. The Change in C-Peptide AUC Following a MMTT From Baseline to Study Completion.

    Time frame: 12 weeks (Baseline and week 12)

    Investigators aim to observe changes in residual endogenous insulin production as measured by C-peptide 2 hour area under the curve following a Mixed Meal Tolerance Test (MMTT). C-peptide is a measure of endogenous insulin secretion as both are secreted in a 1:1 molar ratio. Individuals ingested a liquid meal (Boost) with a fixed amount of protein, fat and carbohydrate in the fasting state followed by the timed measurements of serum C-peptide at 0, 15, 30, 60, 90 and 120 minutes to compute the AUC.

  2. The Change in Hemoglobin A1c From Baseline to Study Completion.

    Time frame: 12 weeks (Baseline and week 12)

    Investigators aim to observe changes in hemoglobin A1c values, a measure of average blood glucose over the preceding 3 months.

  3. The Change in Insulin Use From Baseline to Study Completion.

    Time frame: 12 weeks (Baseline and week 12)

    Exogenous insulin use per kg of body weight.

Sponsors and collaborators

Lead sponsor

University of Colorado, Denver

Other

Collaborators

  • Juvenile Diabetes Research Foundation

Registry information

Official study title

Open Label Pilot Study of the Effect of Methyldopa on MHC-II Antigen Presentation in Type 1 Diabetes

Important dates

Study start
2013
Primary completion
2016
Study completion
2016
First posted
Jun 21, 2013
Registry last updated
Jan 18, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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