Clinical trial NCT03428945: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Type1 Diabetes Mellitus
Keywords: TrialNet
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2018-02-12
Enrollment: 273
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Change From Treatment Assignment Glucose Tolerance to Abnormal Glucose Tolerance or Diabetes
timeFrame: Glucose tolerance is measured every 6 months for up to 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Barbara Davis Center
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: USF Diabetes Center
state: Florida
city: Atlanta
country: United States
facility: Emory Children's Center
state: Georgia
city: Boise
country: United States
facility: St. Luke's Humphreys Diabetes Center
state: Idaho
city: Idaho Falls
country: United States
facility: Rocky Mountain Clinical Research
state: Idaho
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University - Riley Hospital for Children
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky/UK Healthcare
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Pediatric Endocrinology
state: Kentucky
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Las Vegas
country: United States
facility: Palm Research Center, Inc.
state: Nevada
city: Buffalo
country: United States
facility: UBMD Pediatrics
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Syracuse
country: United States
facility: Joslin Center at SUNY Upstate Medical University
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: The University of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Greenville
country: United States
facility: Endocrinology Specialist / Greenville Health System
state: South Carolina
city: Greenville
country: United States
facility: GHS - Pediatric Endocrinology
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Children's Specialty Clinic
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt Eskind Diabetes Clinic
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: Benaroya Research Institute
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: North Adelaide
country: Australia
facility: Women's and Children's Hospital, Adelaide
state: South Australia
city: Parkville
country: Australia
facility: Walter and Eliza Hall Institute of Medical Research
state: Victoria
city: Perth
country: Australia
facility: Perth Children's Hospital
state: Western Australia
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital For Sick Kids
state: Ontario
city: Halifax
country: Canada
facility: IWK Health Center
city: Milan
country: Italy
facility: San Raffaele Hospital
city: Malmö
country: Sweden
facility: Skane University Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: Devon
city: Plymouth
country: United Kingdom
facility: Plymouth Diabetes Clinical Research Unit
state: Devon
city: Harrogate
country: United Kingdom
facility: Harrogate and District NHS Foundation Trust
state: North Yorkshire
city: Bristol
country: United Kingdom
facility: University of Bristol
state: UK
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
Study officials:
affiliation: Type 1 Diabetes TrialNet
name: Carla Greenbaum, MD
role: STUDY_CHAIR
References: