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

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ClinicalTrials.gov Identifier: NCT01883804
Recruitment Status : Completed
First Posted : June 21, 2013
Results First Posted : March 29, 2018
Last Update Posted : May 4, 2018
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Aaron Michels, MD, University of Colorado Denver School of Medicine Barbara Davis Center

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 1
Intervention Drug: Methyldopa
Enrollment 30
Recruitment Details Participants were recruited through the adult clinic of the Barbara Davis Center, University of Colorado School of Medicine. Recruitment began in July of 2013 and concluded in November of 2015.
Pre-assignment Details A total of 30 participants joined the study. Five participants withdrew prior to the first visit or any study procedures. The remaining 25 participants started the study and 20 completed all study visits and procedures.
Arm/Group Title Methyldopa Group
Hide Arm/Group Description

All participants selected to continue with Methyldopa administration.

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

Period Title: Overall Study
Started 25
Completed 20
Not Completed 5
Arm/Group Title Study Group
Hide Arm/Group Description

All participants selected to continue with Methyldopa administration.

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

Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
Analysis population includes those participants that completed the course of the study.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Mean Age Number Analyzed 20 participants
24.75
(18 to 43)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
7
  35.0%
Male
13
  65.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Hispanic or Latino
1
   5.0%
Not Hispanic or Latino
19
  95.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
  10.0%
White
18
  90.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 20 participants
20
 100.0%
Duration of Type 1 Diabetes  
Mean (Full Range)
Unit of measure:  Days
Number Analyzed 20 participants
133
(21 to 566)
Hemoglobin A1c  
Mean (Full Range)
Unit of measure:  Percentage
Number Analyzed 20 participants
7.4
(5.3 to 12.1)
C-Peptide AUC following a 2 Hour Mixed Meal Tolerance Test  
Mean (Full Range)
Unit of measure:  nmol/L/Min
Number Analyzed 20 participants
0.64
(0.10 to 2.67)
Positive Insulin Autoantibodies (Index)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
1
   5.0%
[1]
Measure Description: Only included if measured within 21 days of starting exogenous insulin.
Positive GAD Autoantibodies  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
15
  75.0%
Positive IA-2 Autoantibodies  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
14
  70.0%
Positive ZnT8 Autoantibodies  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
11
  55.0%
Systolic Blood Pressure  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 20 participants
113.2  (10.03)
Diastolic Blood Pressure  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 20 participants
69.65  (8.16)
Elevated AST Values  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
0
   0.0%
Elevated ALT Values  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
0
   0.0%
Abnormal Hemoglobin Levels   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
0
   0.0%
[1]
Measure Description: Hemoglobin < 12 g/dL
1.Primary Outcome
Title The Change From Baseline of DQ8 Antigen Presentation by Peripheral Blood Mononuclear Cells After 6 Weeks of Methyldopa Treatment.
Hide Description 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.
Time Frame 6 Weeks (Baseline and week 6)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Study Group
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open label treatment; dose escalation of methyldopa
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Baseline, α-gliadin/DQ8 642  (104)
6 weeks of treatment, α-gliadin/DQ8 430  (70)
Baseline, insulin/DQ8 27.4  (5.2)
6 weeks of treatment, insulin/DQ8 17.9  (3.3)
2.Secondary Outcome
Title The Change in C-Peptide AUC Following a MMTT From Baseline to Study Completion.
Hide Description 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.
Time Frame 12 weeks (Baseline and week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Study Group
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open label treatment; dose escalation of methyldopa
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: nmol/L/min
Baseline 0.6  (0.5)
Study Completion 0.7  (0.6)
3.Secondary Outcome
Title The Change in Hemoglobin A1c From Baseline to Study Completion.
Time Frame 12 weeks (Baseline and week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Study Group
Hide Arm/Group Description:
open label treatment; dose escalation of methyldopa
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: percentage
Baseline 7.4  (1.6)
Study Completion 6.5  (0.8)
4.Secondary Outcome
Title The Change in Insulin Use From Baseline to Study Completion.
Hide Description Exogenous insulin use per kg of body weight.
Time Frame 12 weeks (Baseline and week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Study Group
Hide Arm/Group Description:
open label treatment; dose escalation of methyldopa
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: units/Kg body weight
Baseline 0.37  (0.20)
Study Completion 0.36  (0.19)
Time Frame Over the course of the 12 week study.
Adverse Event Reporting Description Adverse event collection occurred at each visit through standard questions asked by the research coordinator and discussions with the investigator.
 
Arm/Group Title Study Group
Hide Arm/Group Description

All participants selected to continue with Methyldopa administration.

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

All-Cause Mortality
Study Group
Affected / at Risk (%)
Total   0/25 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Study Group
Affected / at Risk (%) # Events
Total   0/25 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Study Group
Affected / at Risk (%) # Events
Total   5/25 (20.00%)    
General disorders   
Fatigue  1 [1]  5/25 (20.00%)  5
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
A state of generalized weakness with a pronounced inability to summon sufficient energy to accomplish daily activities. Grade 2 are reported.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Aaron Michels
Organization: Barbara Davis Center for Diabetes, University of Colorado School of Medicine
Phone: 303-724-1923
Responsible Party: Aaron Michels, MD, University of Colorado Denver School of Medicine Barbara Davis Center
ClinicalTrials.gov Identifier: NCT01883804     History of Changes
Other Study ID Numbers: 13-1408
First Submitted: June 17, 2013
First Posted: June 21, 2013
Results First Submitted: March 1, 2018
Results First Posted: March 29, 2018
Last Update Posted: May 4, 2018