Trial Outcomes & Findings for Effect of Methyldopa on MHC Class II Antigen Presentation in Type 1 Diabetes (NCT NCT01883804)
NCT ID: NCT01883804
Last Updated: 2022-01-18
Results Overview
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.
COMPLETED
NA
30 participants
6 Weeks (Baseline and week 6)
2022-01-18
Participant Flow
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.
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.
Participant milestones
| Measure |
Methyldopa Group
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 Study
STARTED
|
25
|
|
Overall Study
COMPLETED
|
20
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Methyldopa on MHC Class II Antigen Presentation in Type 1 Diabetes
Baseline characteristics by cohort
| Measure |
Study Group
n=20 Participants
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.
|
|---|---|
|
Age, Continuous
Mean Age
|
24.75 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 Participants
n=5 Participants
|
|
Duration of Type 1 Diabetes
|
133 Days
n=5 Participants
|
|
Hemoglobin A1c
|
7.4 Percentage
n=5 Participants
|
|
C-Peptide AUC following a 2 Hour Mixed Meal Tolerance Test
|
0.64 nmol/L/Min
n=5 Participants
|
|
Positive Insulin Autoantibodies (Index)
|
1 Participants
n=5 Participants
|
|
Positive GAD Autoantibodies
|
15 Participants
n=5 Participants
|
|
Positive IA-2 Autoantibodies
|
14 Participants
n=5 Participants
|
|
Positive ZnT8 Autoantibodies
|
11 Participants
n=5 Participants
|
|
Systolic Blood Pressure
|
113.2 mmHg
STANDARD_DEVIATION 10.03 • n=5 Participants
|
|
Diastolic Blood Pressure
|
69.65 mmHg
STANDARD_DEVIATION 8.16 • n=5 Participants
|
|
Elevated AST Values
|
0 Participants
n=5 Participants
|
|
Elevated ALT Values
|
0 Participants
n=5 Participants
|
|
Abnormal Hemoglobin Levels
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Study Group
n=20 Participants
open label treatment; dose escalation of methyldopa
|
|---|---|
|
The Change From Baseline of DQ8 Antigen Presentation by Peripheral Blood Mononuclear Cells After 6 Weeks of Methyldopa Treatment.
Baseline, α-gliadin/DQ8
|
642 pg/mL
Standard Error 104
|
|
The Change From Baseline of DQ8 Antigen Presentation by Peripheral Blood Mononuclear Cells After 6 Weeks of Methyldopa Treatment.
6 weeks of treatment, α-gliadin/DQ8
|
430 pg/mL
Standard Error 70
|
|
The Change From Baseline of DQ8 Antigen Presentation by Peripheral Blood Mononuclear Cells After 6 Weeks of Methyldopa Treatment.
Baseline, insulin/DQ8
|
27.4 pg/mL
Standard Error 5.2
|
|
The Change From Baseline of DQ8 Antigen Presentation by Peripheral Blood Mononuclear Cells After 6 Weeks of Methyldopa Treatment.
6 weeks of treatment, insulin/DQ8
|
17.9 pg/mL
Standard Error 3.3
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Study Group
n=20 Participants
open label treatment; dose escalation of methyldopa
|
|---|---|
|
The Change in C-Peptide AUC Following a MMTT From Baseline to Study Completion.
Baseline
|
0.6 nmol/L/min
Standard Deviation 0.5
|
|
The Change in C-Peptide AUC Following a MMTT From Baseline to Study Completion.
Study Completion
|
0.7 nmol/L/min
Standard Deviation 0.6
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Study Group
n=20 Participants
open label treatment; dose escalation of methyldopa
|
|---|---|
|
The Change in Hemoglobin A1c From Baseline to Study Completion.
Baseline
|
7.4 percentage
Standard Deviation 1.6
|
|
The Change in Hemoglobin A1c From Baseline to Study Completion.
Study Completion
|
6.5 percentage
Standard Deviation 0.8
|
SECONDARY outcome
Timeframe: 12 weeks (Baseline and week 12)Exogenous insulin use per kg of body weight.
Outcome measures
| Measure |
Study Group
n=20 Participants
open label treatment; dose escalation of methyldopa
|
|---|---|
|
The Change in Insulin Use From Baseline to Study Completion.
Baseline
|
0.37 units/Kg body weight
Standard Deviation 0.20
|
|
The Change in Insulin Use From Baseline to Study Completion.
Study Completion
|
0.36 units/Kg body weight
Standard Deviation 0.19
|
Adverse Events
Study Group
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Study Group
n=25 participants at risk
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.
|
|---|---|
|
General disorders
Fatigue
|
20.0%
5/25 • Number of events 5 • Over the course of the 12 week study.
Adverse event collection occurred at each visit through standard questions asked by the research coordinator and discussions with the investigator.
|
Additional Information
Dr. Aaron Michels
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place