Diabetes Mellitus, Type 1
Conditions
Keywords
diabetes, juvenile diabetes, type 1 diabetes, diabetes mellitus, recent onset, new onset
Brief summary
This is a phase I trial in individuals who have been diagnosed with type 1 diabetes within the previous 3-48 months. The study is testing whether two immune system modifying drugs are safe when used in combination and if they have immune altering effects that indicate they can halt the progression of type 1 diabetes progression.
Detailed description
At the time of diagnosis with type 1 diabetes, 15-40% of beta cells may remain active and healthy in the pancreas, capable of producing insulin the body needs to regulate blood glucose levels. Because even small amounts of natural insulin production can decrease the long term effects of diabetes, it is essential that these cells are preserved. This trial will test whether a combination of the drugs Proleukin (IL-2) and Rapamune (sirolimus) may be safely administered to recently diagnosed type 1 diabetes patients and whether it causes changes to the immune system that can halt the autoimmune destruction of the remaining beta cells. This drug combination has been found to be effective for long-term diabetes prevention in mouse models of type 1 diabetes. This study is a phase I study for individuals 18-45 years of age who have been diagnosed with type 1 diabetes in the past 3-48 months. All participants will be treated with Proleukin (administered subcutaneously 3x per week) for 28 days and Rapamune (taken orally, daily) for 12 weeks. The study will last for 12 months, with additional follow-up of 24 months. The majority of study visits occur within the first 6 months. Mixed meal tolerance tests, in which participants take a milkshake-like drink and have blood sampled over a 2 or 4-hour period, will take place during an initial screening visit and three additional times during the first year. All participants will also receive intensive diabetes management designed to maintain stable blood glucose levels.
Interventions
DRUGIL-2
Administered by subcutaneous injection at a dose of 4.5x10\^6 IU/day, three times weekly for 28 days starting on day 0.
DRUGRapamycin
Administered orally, initial daily dose of 2mg. At day 7, dose adjusted to achieve and maintain whole blood trough levels of 5-10 ng/ml.
Sponsors
Immune Tolerance Network (ITN)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with type 1 diabetes (per ADA criteria) more than 3 but less than 48 months prior to enrollment; * 18 to 45 years of age;and * Positive for at least one islet cell autoantibody (GAD65-antibody, CA512-antibody and/or ICA).
Exclusion criteria
* Chronic use of glucocorticoids or other immunosuppressive ages 4 weeks before enrollment; * History of recurrent infections, other autoimmune diseases, cardiac disease, cataracts or other chronic medical conditions that investigators believe could compromise participant safety; * Females who are pregnant, lactating intend to get pregnant, or are unwilling to undergo pregnancy testing during the study; * Males who intend to father a pregnancy during the first 6 months of the study; or * Participation in another clinical study within the last 30 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of adverse events and laboratory anomalies | through day 364 |
Secondary
| Measure | Time frame |
|---|---|
| AUC for C-peptide responses following MMTT | various |
| Frequency of severe hypoglycemia | various |
| Insulin dose in units per kilogram | various |
| HbA1c levels | various |
Countries
United States
Outcome results
None listed