Clinical trial NCT01319331: The Effects of Alpha-1 Antitrypsin (AAT) on 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Type 1 Diabetes
Keywords: diabetes
type 1 diabetes
AAT
Alpha-1 Antitrypsin
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Omni Bio Pharmaceutical, Inc.
First posted: 2011-03-21
Enrollment: 12
Sex: ALL
Minimum age (years): 6
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: To assess participant safety & feasibility of study drug administration
timeFrame: Study duration is 2 years
Secondary outcomes:
measure: To assess AAT treatment on the maintenance of c-peptide production
timeFrame: Stimulated c-peptide at year one and two.
measure: Assess the effects of AAT on glycemic variability and A1c.
timeFrame: Continuous Glucose Monitoring at one and two years.
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Barbara Davis Center for Childhood Diabetes
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Peter A Gottlieb, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ozeri E, Mizrahi M, Shahaf G, Lewis EC. alpha-1 antitrypsin promotes semimature, IL-10-producing and readily migrating tolerogenic dendritic cells. J Immunol. 2012 Jul 1;189(1):146-53. doi: 10.4049/jimmunol.1101340. Epub 2012 May 25.