Hydroxychloroquine in Individuals At-risk for Type 1 Diabetes Mellitus (TN-22)

• ClinicalTrials.gov Identifier: NCT03428945
• Recruitment Status: Terminated
• First Posted: February 12, 2018
• Last Update Posted: December 28, 2022
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborator: Juvenile Diabetes Research Foundation
• Information provided by (Responsible Party): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Tracking Information

• First Submitted Date: January 24, 2018
• First Posted Date: February 12, 2018
• Last Update Posted Date: December 28, 2022
• Actual Study Start Date: August 15, 2018
• Actual Primary Completion Date: July 11, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 12, 2019)

Change from Treatment Assignment Glucose Tolerance to Abnormal Glucose Tolerance or Diabetes [ Time Frame: Glucose tolerance is measured every 6 months for approximately 6 years ]

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.

Original Primary Outcome Measures (submitted: February 8, 2018)

Progression to Abnormal Glucose Tolerance or Diabetes [ Time Frame: Study duration is based on events observed; the duration is estimated to be approximately 6 years ]

The primary outcome is the time from treatment assignment to development of abnormal glucose tolerance or diagnosis of type 1 diabetes

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Investigator)
Masking Description:

Active drug and placebo will be identical in appearance and packaging

Primary Purpose: Prevention

• Condition: Type1 Diabetes Mellitus

Intervention

• Drug: Hydroxychloroquine
  Hydroxychloroquine for oral administration, dosed by weight
  Other Name: Plaquenil
• Drug: Placebo
  Placebo tablet identical to active drug
  Other Name: Inactive Drug

Study Arms

• Experimental: Hydroxychloroquine
  Hydroxychloroquine compound for oral use
  Intervention: Drug: Hydroxychloroquine
• Placebo Comparator: Placebo
  Placebo tablet matching active drug
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 19, 2022): 275
• Original Estimated Enrollment (submitted: February 8, 2018): 201
• Actual Study Completion Date: November 1, 2022
• Actual Primary Completion Date: July 11, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Participant in TrialNet Pathway to Prevention Study (TN01)
2. Age 3 years or greater at the time of randomization
3. Willing to provide informed consent
4. Normal glucose tolerance by OGTT within 7 weeks (no more than 52 days) of baseline
5. Two or more diabetes-related autoantibodies present on two separate samples
6. Weight of 12 kg or greater at screening
7. If a female participant with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing prior to randomization and at each study visit
8. Anticipated ability to swallow study medication.

Exclusion Criteria:

1. Abnormal Glucose Tolerance or Diabetes
2. History of treatment with insulin or other diabetes therapies
3. Ongoing use of medications known to influence glucose tolerance
4. Ongoing or anticipated future use of medications known to have untoward interactions with hydroxychloroquine
5. Known hypersensitivity to 4-aminoquinoline compounds
6. G6PD deficiency
7. History of retinopathy
8. Have an active infection at time of randomization
9. Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B core antibody or surface antigen), or Hepatitis C infection
10. 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.
11. 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.
12. Be pregnant or breastfeeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Italy, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT03428945
• Other Study ID Numbers: Hydroxychloroquine; UC4DK117009 ( U.S. NIH Grant/Contract ); UC4DK106993 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Original Responsible Party: Same as current
• Current Study Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Original Study Sponsor: Same as current
• Collaborators: Juvenile Diabetes Research Foundation

Investigators

• Study Chair: Carla Greenbaum, MD; Type 1 Diabetes TrialNet

• PRS Account: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Verification Date: December 2022