Methyldopa for Reduction of DQ8 Antigen Presentation in At-Risk Subjects for Type 1 Diabetes (TN-23)
Primary Purpose
Type1 Diabetes Mellitus
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Methyldopa
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Type1 Diabetes Mellitus focused on measuring TrialNet
Eligibility Criteria
Inclusion Criteria:
- Participant in TrialNet Pathway to Prevention Study (TN01)
- Willing to provide Informed Consent or, if the subject is <18 years of age, have a parent or legal guardian provide Informed Consent
- Confirmed positive for one or more autoantibodies, one of which is insulin autoantibody (mIAA)
- Positive for at least one gene encoding HLA-DQ8 (DQB*0302)
- If a female participant with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing prior to randomization and during the study
- Have normal or abnormal glucose tolerance on OGTT performed within 7 weeks of randomization
Exclusion Criteria:
- Inability or unwillingness of a participant to give written informed consent or comply with study protocol
- History of clinically significant anemia or Hemoglobin <10 g/dl
- Evidence of liver dysfunction
- History of renal insufficiency
- History of symptomatic hypotension including positional hypotension
- Systolic BP < 100 mmHg for adults or blood pressure < 5th percentile for age/height/gender in children and adolescents
- Use of a treatment that is known to cause a significant, ongoing change in the course of diabetes or immunologic status, within 4 weeks prior to participation. This includes high-dose inhaled, extensive topical or systemic glucocorticoids
- Females who are pregnant at the time of screening, breastfeeding or unwilling to defer pregnancy during the 16-month study period. (Female participant must be at least 100 days postpartum before enrollment into study)
- Unable to avoid concurrent antihypertensive medications, monoamine oxidase (MAO) inhibitors, lithium, or medications containing ferrous sulfate or ferrous gluconate
- Unable to avoid medications that affect stomach pH, such as proton pump inhibitors or histamine H2 receptor blockers
- Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Methyldopa
Placebo
Arm Description
Adults: methyldopa 500mg twice daily for one week and then increased to 500mg three times a day Children: methyldopa dose based on weight twice daily for one week then increased to three times a day
Inactive agent to match active drug in appearance and dose frequency.
Outcomes
Primary Outcome Measures
DQ8 Antigen Presentation
insulin peptide-specific DQ8 antigen presentation
Secondary Outcome Measures
Full Information
NCT ID
NCT03396484
First Posted
January 4, 2018
Last Updated
June 26, 2020
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT03396484
Brief Title
Methyldopa for Reduction of DQ8 Antigen Presentation in At-Risk Subjects for Type 1 Diabetes
Acronym
TN-23
Official Title
Methyldopa for Reduction of DQ8 Antigen Presentation in At-Risk Subjects for Type 1 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Study not begun due to continued laboratory work on the feasibility of outcome measures.
Study Start Date
September 2020 (Anticipated)
Primary Completion Date
March 2022 (Anticipated)
Study Completion Date
March 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A study is to see if methyldopa can change the immune system's attack on insulin producing cells in people at early stages of type 1 diabetes.
Detailed Description
The study is a randomized, double blinded, placebo-controlled, multi-center crossover clinical trial.
Eligible subjects will be randomized in a 1:1 allocation ratio to one of two treatment schedules: first methyldopa then placebo vs. first placebo then methyldopa.
The study objective is to assess the safety, efficacy, and mode of action of methyldopa to reduce DQ8 antigen presentation in individuals at Stage 1 and 2 of type 1 diabetes (T1D).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type1 Diabetes Mellitus
Keywords
TrialNet
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Methyldopa
Arm Type
Experimental
Arm Description
Adults: methyldopa 500mg twice daily for one week and then increased to 500mg three times a day
Children: methyldopa dose based on weight twice daily for one week then increased to three times a day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Inactive agent to match active drug in appearance and dose frequency.
Intervention Type
Drug
Intervention Name(s)
Methyldopa
Other Intervention Name(s)
Aldomet
Intervention Description
Tablet for oral dosing
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablet for oral dosing
Primary Outcome Measure Information:
Title
DQ8 Antigen Presentation
Description
insulin peptide-specific DQ8 antigen presentation
Time Frame
6 months after initiation of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant in TrialNet Pathway to Prevention Study (TN01)
Willing to provide Informed Consent or, if the subject is <18 years of age, have a parent or legal guardian provide Informed Consent
Confirmed positive for one or more autoantibodies, one of which is insulin autoantibody (mIAA)
Positive for at least one gene encoding HLA-DQ8 (DQB*0302)
If a female participant with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing prior to randomization and during the study
Have normal or abnormal glucose tolerance on OGTT performed within 7 weeks of randomization
Exclusion Criteria:
Inability or unwillingness of a participant to give written informed consent or comply with study protocol
History of clinically significant anemia or Hemoglobin <10 g/dl
Evidence of liver dysfunction
History of renal insufficiency
History of symptomatic hypotension including positional hypotension
Systolic BP < 100 mmHg for adults or blood pressure < 5th percentile for age/height/gender in children and adolescents
Use of a treatment that is known to cause a significant, ongoing change in the course of diabetes or immunologic status, within 4 weeks prior to participation. This includes high-dose inhaled, extensive topical or systemic glucocorticoids
Females who are pregnant at the time of screening, breastfeeding or unwilling to defer pregnancy during the 16-month study period. (Female participant must be at least 100 days postpartum before enrollment into study)
Unable to avoid concurrent antihypertensive medications, monoamine oxidase (MAO) inhibitors, lithium, or medications containing ferrous sulfate or ferrous gluconate
Unable to avoid medications that affect stomach pH, such as proton pump inhibitors or histamine H2 receptor blockers
Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carla Greenbaum, MD
Organizational Affiliation
Type 1 Diabetes TrialNet
Official's Role
Study Chair
12. IPD Sharing Statement
Links:
URL
https://www.trialnet.org/
Description
TrialNet Public Website
Learn more about this trial
Methyldopa for Reduction of DQ8 Antigen Presentation in At-Risk Subjects for Type 1 Diabetes
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