the effects of alpha-1 antitrypsin (aat) on the progression of type 1 diabetes

Conditions: Diabetes; Type 1 Diabetes

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.


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

Keywords: diabetes type 1 diabetes aat alpha-1 antitrypsin