Type 1 Diabetes
Conditions
Keywords
oral insulin
Brief summary
The study is a 2 arm, multi-center, randomized, open-labeled clinical trial designed to assess the effects of varying doses and schedules of oral insulin on immunological and metabolic markers in relatives at risk for type 1 diabetes (T1D).
Detailed description
A minimum of 40 eligible participants will be identified for study participation from the TrialNet Pathway to Prevention study. Participants must have a relative with type 1 diabetes and be positive for insulin autoantibodies and at least one other autoantibody. All participants will receive active treatment of recombinant insulin treatment in capsules of either 67.5 mg daily or 500mg every other week. Participants will need to visit the study site up to eleven times over one year for blood tests and other study procedures. During the beginning treatment phase there are two visits one month apart for those given the 67.5 mg dose, and three visits two weeks apart to titrate the dose for those in the 500mg treatment group. There are three additional treatment visits at months 2, 3, and 6 and 4 additional visits for follow-up at months 7, 8, 9 and 12. The primary outcome is the change in immune function as assessed by change in level or quality of T lymphocyte or autoantibody biomarkers measured between 13 and 26 weeks compared to baseline. .
Interventions
DRUG67.5 mg oral insulin crystals daily
human insulin crystals in capsules
DRUG500mg oral insulin crystals every other week
human insulin crystals in capsules
Sponsors
Type 1 Diabetes TrialNet
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Participants in TrialNet Natural History/Pathway to Prevention Study (TN01); is relative of proband with type 1 diabetes * Between ages 3-45 with normal Oral Glucose Tolerance Test (OGTT) or between ages 3-7 with an abnormal OGTT * Confirmed positive for insulin autoantibodies within previous six months * Confirmed positive for one or more other autoantibodies on two separate occasions within the past six months
Exclusion criteria
* Diagnosed with type 1 diabetes * History of treatment with insulin or oral hypoglycemic agent * History of therapy with immunosuppressive drugs or non-physiologic glucocorticoids within the past two years for a period of more than three months * Ongoing use of medications known to influence glucose tolerance * Pregnant or intending to become pregnant while on study or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in GAD65 Autoantibody Titer (DK Units/mL) | 13 and 26 weeks after first dose versus baseline | Change in T-lymphocyte (GAD65) biomarker of beta cell specific immune response |
| Change in mIAA Autoantibody Titer From Baseline | 13 and 26 weeks after first dose versus baseline | Micro-islet autoantibodies (mIAA) autoantibody titers are a measure of of beta cell immune response |
Countries
Australia, Canada, Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 67.5 mg Oral Insulin Crystals Daily 67.5 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given daily for six months
67.5 mg oral insulin crystals daily: human insulin crystals in capsules | 45 |
| 500mg Oral Insulin Crystals Every Other Week 500 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given every other week for six months
500mg oral insulin crystals every other week: human insulin crystals in capsules | 47 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | 67.5 mg Oral Insulin Crystals Daily | Total | 500mg Oral Insulin Crystals Every Other Week |
|---|---|---|---|
| Age, Continuous | 8.9 years | 8.1 years | 7.9 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 83 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Glucose Tolerance Abnormal Glucose Tolerance | 9 Participants | 20 Participants | 11 Participants |
| Glucose Tolerance Normal Glucose Tolerance | 36 Participants | 72 Participants | 36 Participants |
| HLA DR3 Absent | 31 Participants | 58 Participants | 27 Participants |
| HLA DR3 Present | 14 Participants | 33 Participants | 19 Participants |
| HLA DR3 Unknown | 0 Participants | 1 Participants | 1 Participants |
| HLA DR4 Absent | 22 Participants | 37 Participants | 15 Participants |
| HLA DR4 Present | 23 Participants | 54 Participants | 31 Participants |
| HLA DR4 Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 42 Participants | 84 Participants | 42 Participants |
| Relationship to person with type 1 diabetes Child | 1 Participants | 3 Participants | 2 Participants |
| Relationship to person with type 1 diabetes Other | 4 Participants | 8 Participants | 4 Participants |
| Relationship to person with type 1 diabetes Parent | 6 Participants | 18 Participants | 12 Participants |
| Relationship to person with type 1 diabetes Sibling | 34 Participants | 63 Participants | 29 Participants |
| Sex: Female, Male Female | 20 Participants | 41 Participants | 21 Participants |
| Sex: Female, Male Male | 25 Participants | 51 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 47 |
| other Total, other adverse events | 25 / 45 | 24 / 47 |
| serious Total, serious adverse events | 0 / 45 | 0 / 47 |
Outcome results
Primary
Change in GAD65 Autoantibody Titer (DK Units/mL)
Change in T-lymphocyte (GAD65) biomarker of beta cell specific immune response
Time frame: 13 and 26 weeks after first dose versus baseline
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 67.5 mg Oral Insulin Crystals Daily | Change in GAD65 Autoantibody Titer (DK Units/mL) | 13 weeks | 247 DK Units/mL |
| 67.5 mg Oral Insulin Crystals Daily | Change in GAD65 Autoantibody Titer (DK Units/mL) | 26 weeks | 193 DK Units/mL |
| 500 mg Oral Insulin Crystals Every Other Week | Change in GAD65 Autoantibody Titer (DK Units/mL) | 13 weeks | 234 DK Units/mL |
| 500 mg Oral Insulin Crystals Every Other Week | Change in GAD65 Autoantibody Titer (DK Units/mL) | 26 weeks | 196 DK Units/mL |
Primary
Change in mIAA Autoantibody Titer From Baseline
Micro-islet autoantibodies (mIAA) autoantibody titers are a measure of of beta cell immune response
Time frame: 13 and 26 weeks after first dose versus baseline
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 67.5 mg Oral Insulin Crystals Daily | Change in mIAA Autoantibody Titer From Baseline | 13 weeks | 0.021 DK Units/mL |
| 67.5 mg Oral Insulin Crystals Daily | Change in mIAA Autoantibody Titer From Baseline | 26 weeks | 0.020 DK Units/mL |
| 500 mg Oral Insulin Crystals Every Other Week | Change in mIAA Autoantibody Titer From Baseline | 13 weeks | 0.020 DK Units/mL |
| 500 mg Oral Insulin Crystals Every Other Week | Change in mIAA Autoantibody Titer From Baseline | 26 weeks | 0.017 DK Units/mL |