Proleukin and Rapamune in Type 1 Diabetes

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase I Trial of Proleukin and Rapamune in Recent-onset Type 1 Diabetes Mellitus (ITN018AI)

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: IL-2
* Drug: Rapamycin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapamycin/IL-2 combination therapy<br>IL-2 (Proleukin) was administered at 4.5 3 106 IU s.c., three times per week for 4 weeks for a total of 12 doses. Rapamycin (Rapamune or Sirolimus) was administered without a loading dose at 2 mg/day, with adjustments to maintain trough blood levels of 5-10 ng/mL for 3 months. | Drug: IL-2<br>* Administered by subcutaneous injection at a dose of 4.5x10^6 IU/day, three times weekly for 28 days starting on day 0.<br>* Other names: Proleukin;Drug: Rapamycin<br>* 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.<br>* Other names: Sirolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events and laboratory anomalies |  | through day 364 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, juvenile diabetes, type 1 diabetes, diabetes mellitus, recent onset, new onset