Type1 Diabetes Mellitus
Conditions
Keywords
TrialNet
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.
Interventions
DRUGHydroxychloroquine
Hydroxychloroquine for oral administration, dosed by weight
DRUGPlacebo
Placebo tablet identical to active drug
Sponsors
Juvenile Diabetes Research Foundation
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
Active drug and placebo will be identical in appearance and packaging
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.
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Treatment Assignment Glucose Tolerance to Abnormal Glucose Tolerance or Diabetes | Glucose tolerance is measured every 6 months for up to 4 years | The primary outcome is the time in months from random treatment assignment to the development of confirmed abnormal glucose tolerance or clinical diabetes. |
Countries
Australia, Canada, Italy, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydroxychloroquine Hydroxychloroquine compound for oral use
Hydroxychloroquine: Hydroxychloroquine for oral administration, dosed by weight | 183 |
| Placebo Placebo tablet matching active drug
Placebo: Placebo tablet identical to active drug | 90 |
| Total | 273 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 3 |
| Overall Study | Withdrawal by Subject | 10 | 10 |
Baseline characteristics
| Characteristic | Placebo | Hydroxychloroquine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 77 Participants | 165 Participants | 242 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 18 Participants | 31 Participants |
| Age, Continuous | 10.9 years | 11.7 years | 11.3 years |
| Autoantibodies positive 1 positive Autoantibody | 1 Participants | 2 Participants | 3 Participants |
| Autoantibodies positive 2 positive Autoantibodies | 23 Participants | 35 Participants | 58 Participants |
| Autoantibodies positive 3 positive Autoantibodies | 24 Participants | 39 Participants | 63 Participants |
| Autoantibodies positive 4 positive Autoantibodies | 18 Participants | 46 Participants | 64 Participants |
| Autoantibodies positive 5 positive Autoantibodies | 24 Participants | 61 Participants | 85 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 15 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants | 162 Participants | 244 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 8 Participants | 10 Participants |
| Race (NIH/OMB) White | 83 Participants | 171 Participants | 254 Participants |
| Region of Enrollment Australia | 7 participants | 13 participants | 20 participants |
| Region of Enrollment Canada | 7 participants | 9 participants | 16 participants |
| Region of Enrollment Finland | 0 participants | 3 participants | 3 participants |
| Region of Enrollment Italy | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Sweden | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United Kingdom | 2 participants | 2 participants | 4 participants |
| Region of Enrollment United States | 72 participants | 155 participants | 227 participants |
| Relationship to person with Type 1 Diabetes More than one first degree relative | 6 Participants | 15 Participants | 21 Participants |
| Relationship to person with Type 1 Diabetes No Relatives | 3 Participants | 10 Participants | 13 Participants |
| Relationship to person with Type 1 Diabetes Offspring | 5 Participants | 6 Participants | 11 Participants |
| Relationship to person with Type 1 Diabetes Parent(s) | 22 Participants | 42 Participants | 64 Participants |
| Relationship to person with Type 1 Diabetes Second Degree Relative | 6 Participants | 9 Participants | 15 Participants |
| Relationship to person with Type 1 Diabetes Sibling(s) | 48 Participants | 100 Participants | 148 Participants |
| Relationship to person with Type 1 Diabetes Third Degree Relative | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 33 Participants | 61 Participants | 94 Participants |
| Sex: Female, Male Male | 57 Participants | 122 Participants | 179 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 183 | 0 / 90 |
| other Total, other adverse events | 125 / 183 | 61 / 90 |
| serious Total, serious adverse events | 5 / 183 | 1 / 90 |
Outcome results
Primary
Change From Treatment Assignment Glucose Tolerance to Abnormal Glucose Tolerance or Diabetes
The primary outcome is the time in months from random treatment assignment to the development of confirmed abnormal glucose tolerance or clinical diabetes.
Time frame: Glucose tolerance is measured every 6 months for up to 4 years
Population: Participants included in the time-to-event analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydroxychloroquine | Change From Treatment Assignment Glucose Tolerance to Abnormal Glucose Tolerance or Diabetes | 19.7 Months |
| Placebo | Change From Treatment Assignment Glucose Tolerance to Abnormal Glucose Tolerance or Diabetes | 18.8 Months |