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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Withdrawn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

About this trial

This is an interventional prevention trial for Type1 Diabetes Mellitus focused on measuring TrialNet

Eligibility Criteria

8 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

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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