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

Phase 1

Completed

• Conditions: Diabetes; Type 1 Diabetes
• Interventions: Drug: Alpha 1-Antitrypsin (AAT, Aralast NP)

• Registration Number: NCT01319331
• Lead Sponsor: University of Colorado, Denver

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10
• Study First Submitted: 2011-03-17
• Study First Submitted QC: 2011-03-18
• Study First Posted: 2011-03-21
• Primary Completion: 2015-10
• Study Completion: 2016-05
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-23
• Last Update Posted: 2017-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Alpha-1 Antitrypsin (AAT, Aralast NP)	Alpha 1-Antitrypsin (AAT, Aralast NP)	Alpha-1 Antitrypsin (AAT, Aralast NP) as prescribed for study duration

Primary Outcome Measures

Name	Time	Method
To assess participant safety & feasibility of study drug administration	Study duration is 2 years

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Barbara Davis Center for Childhood Diabetes; 🇺🇸 Aurora, Colorado, United States