Hydroxychloroquine in Individuals At-risk for Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The study is a 2-arm, double blinded, multicenter, 2:1 randomized, placebo controlled clinical trial. Subjects will receive hydroxychloroquine or placebo and close monitoring for progression of T1D.

Detailed Description
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This study is testing a medication, called hydroxychloroquine (HCQ) to assess safety and effectiveness to prevent individuals at risk of type 1 diabetes (T1D) from progressing to type 1 diabetes. HCQ is approved by the U.S. Food and Drug Administration as a treatment for malaria, lupus, and rheumatoid arthritis. HCQ has been used extensively for treatment of autoimmune disease in adults, children, and during pregnancy. This medication has not previously been studied as a treatment to prevent T1D. The goal of this study is to learn if HCQ can help prevent or delay progression from normal glucose tolerance (Stage 1) to abnormal glucose tolerance (Stage 2) or type 1 diabetes (Stage 3). The study involves 5 visits in the first 6 months, then 1 visit every 6 months for the remainder of the study.

Official Title
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Hydroxychloroquine for Prevention of Abnormal Glucose Tolerance and Diabetes in Individuals At-risk for Type 1 Diabetes Mellitus (T1D)

Conditions
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Type1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant in TrialNet Pathway to Prevention Study (TN01) Age 3 years or greater at the time of randomization Willing to provide informed consent Normal glucose tolerance by OGTT within 7 weeks (no more than 52 days) of baseline Two or more diabetes-related autoantibodies present on two separate samples Weight of 12 kg or greater at screening If a female participant with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing prior to randomization and at each study visit Anticipated ability to swallow study medication. Exclusion Criteria: Abnormal Glucose Tolerance or Diabetes History of treatment with insulin or other diabetes therapies Ongoing use of medications known to influence glucose tolerance Ongoing or anticipated future use of medications known to have untoward interactions with hydroxychloroquine Known hypersensitivity to 4-aminoquinoline compounds G6PD deficiency History of retinopathy Have an active infection at time of randomization Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B core antibody or surface antigen), or Hepatitis C infection Deemed unlikely or unable to comply with the protocol or have any complicating medical issues, including prolonged QT interval, a disease previously or likely in the future to require immunosuppression, or abnormal clinical laboratory results that interfere with study conduct or cause increased risk. Deemed unlikely or unable to comply with the protocol or have any complicating medical issues, including prolonged QT interval, a disease previously or likely in the future to require immunosuppression, or abnormal clinical laboratory results that interfere with study conduct or cause increased risk. Be pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Treatment assignment (active drug: placebo) will be assigned in a parallel, randomized, 2:1 model. Assignment will be stratified based on prior treatment for T1D prevention and age.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine<br>Hydroxychloroquine compound for oral use | Drug: Hydroxychloroquine<br>* Hydroxychloroquine for oral administration, dosed by weight<br>* Other names: Plaquenil;|
| Placebo Comparator: Placebo<br>Placebo tablet matching active drug | Drug: Placebo<br>* Placebo tablet identical to active drug<br>* Other names: Inactive Drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Treatment Assignment Glucose Tolerance to Abnormal Glucose Tolerance or Diabetes | The primary outcome is the time from treatment assignment to changes in glucose tolerance. The time to development of abnormal glucose tolerance or the diagnosis of type 1 diabetes will be measured to identify these changes. | Glucose tolerance is measured every 6 months for approximately 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TrialNet