Methyldopa for Reduction of DQ8 Antigen Presentation in At-Risk Subjects for Type 1 Diabetes

NCT ID: NCT03396484

Last Updated: 2020-06-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-30
• Study Completion Date: 2022-03-31

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).

Conditions

Type1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Methyldopa

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

Group Type: EXPERIMENTAL

Methyldopa

Intervention Type: DRUG

Tablet for oral dosing

Placebo

Inactive agent to match active drug in appearance and dose frequency.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablet for oral dosing

Interventions

Methyldopa

Tablet for oral dosing

Intervention Type: DRUG

Placebo

Tablet for oral dosing

Intervention Type: DRUG

Other Intervention Names

Aldomet

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

• Minimum Eligible Age: 8 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carla Greenbaum, MD

Role: STUDY_CHAIR

Type 1 Diabetes TrialNet

Related Links

https://www.trialnet.org/

TrialNet Public Website

Other Identifiers

UC4DK106993

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UC4DK117009

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Methyldopa

Identifier Type: -

Identifier Source: org_study_id