The Effects of Alpha-1 Antitrypsin (AAT) on the Progression of Type 1 Diabetes

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if the drug Alpha-1 Antitrypsin (AAT, Aralast NP) will preserve beta-cell function and help slow the progression of type 1 diabetes.

Official Title
-----------------
The Effects of Open Label Alpha-1 Antitrypsin on the Progression of Type 1 Diabetes in Subjects With Detectable C-peptide

Conditions
-----------------
Diabetes, Type 1 Diabetes

Intervention / Treatment
-----------------
* Drug: Alpha 1-Antitrypsin (AAT, Aralast NP)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of Type 1 Diabetes Mellitus based on ADA Criteria for fewer than 5 years but more than 100 days 6-45 years of age, inclusive. To assess safety, we will initially enroll 8 patients over the age of 16. Following the last infusion of the 8th patient, we will assess adverse events. As long as there are no stopping criteria met for these 8 patients we will decrease the age criteria down to 6 years old. C-peptide increase during screening mixed meal tolerance test with a minimal stimulated value of ≥ 0.2 pmol/mL. Positive for antibodies to insulin (if insulin autoantibody positive only, determination must be within two weeks of insulin initiation), GAD-65, IA-2 or ZnT8 Agree to intensive management of diabetes with an HgbA1c goal of < 7.0% If female, (a) surgically sterile or (b) postmenopausal or (c) if of reproductive potential, willing to use medically acceptable birth control (e.g. female hormonal contraception, barrier methods or sterilization. ) until 3 months after completion of any treatment period If male and of reproductive potential, willing to use medically acceptable birth control until 3 months after completion of any treatment period, unless the female partner is postmenopausal or surgically sterile Serum creatinine ≤ 1.5 x upper limit of normal AST < 2 times the upper limit of normal Hematology:WBC > 3000 x 109/L; platelets > 100 x 109/L; hemoglobin > 10.0 g/dL. Exclusion Criteria: Unable or unwilling to comply with the requirements of the study protocol Body Mass Index (BMI) > 30 kg/m2 Unstable blood sugar control defined as one or more episodes of severe hypoglycemia (defined as hypoglycemia that required the assistance of another person) within the last 30 days Previous immunotherapy for T1D Administration of an experimental agent for T1D at any time or use of an experimental device for T1D within 30 days of screening, unless approved by the study PI History of any organ transplant, including islet cell transplant Active autoimmune or immune deficiency disorder (e.g. sarcoidosis, rheumatoid arthritis) Serum bilirubin > ULN, except those subjects whose abnormal values were attributed to any stable, benign condition (such as Gilbert's Syndrome) may be included TSH outside the normal range at screening, except those subjects on stable doses of thyroid hormone replacement therapy may be included Known HIV positivity, active hepatitis B or active hepatitis C infection Anticipated pregnancy during active dosing or within 3 months after completion of active dosing phase History of a malignant neoplasm within the previous 5 years (except in situ cervical cancer and curable non-melanoma skin malignancy) Any social condition or medical condition that would, in the opinion of the investigator, prevent complete participation in the study or that would pose a significant hazard to the subjects' participation History of active substance abuse within 12 months of screening A psychiatric or medical disorder that would prevent giving informed consent Individuals with a history of IgA deficiency Individuals with a history of hypersensitivity to AAT

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alpha-1 Antitrypsin (AAT, Aralast NP)<br>Alpha-1 Antitrypsin (AAT, Aralast NP) as prescribed for study duration | Drug: Alpha 1-Antitrypsin (AAT, Aralast NP)<br>* Eligible subjects will be treated once a week for 8 weeks (8 total treatments).<br>* Other names: Aralast NP;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess participant safety & feasibility of study drug administration |  | Study duration is 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess AAT treatment on the maintenance of c-peptide production |  | Stimulated c-peptide at year one and two. | 
| Assess the effects of AAT on glycemic variability and A1c. |  | Continuous Glucose Monitoring at one and two years. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
diabetes, type 1 diabetes, AAT, Alpha-1 Antitrypsin