A Research Trial of Aralast NP in New Onset Diabetes (RETAIN) - Part II
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Purpose
Aralast NP (alpha-1 antitrypsin, AAT), an alpha-1 proteinase inhibitor (human), was the drug to be tested in this clinical trial. Aralast NP is an anti-inflammatory drug that affects the cells that are thought to be involved in the development of type 1 diabetes mellitus (T1DM, T1D). This study, known as RETAIN, was planned as a two-part trial to investigate the effect of Aralast NP on preserving beta cell function and to determine if the intervention would slow the progression of type 1 diabetes.
Part I of this trial (NCT 01183468) was an open-label, safety and dose level study consisting of two groups. After completion of Part I, including a satisfactory safety review, enrollment in Part II was to begin. Part II was designed as a two-arm, double-blind, placebo-controlled clinical trial, and participants were to be randomly assigned to either the Aralast NP treatment or placebo group.
| Condition | Intervention | Phase |
|---|---|---|
|
Diabetes Mellitus, Type 1 |
Drug: Aralast NP Drug: Placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)- Part II |
- Mixed-Meal Tolerance Test (MMTT)-Stimulated 2-hour C-peptide Area Under the Curve (AUC) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
- MMTT-Stimulated Peak and 4-hour C-peptide AUC [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
- MMTT-Stimulated 2-hour C-Peptide AUC Assessed Over Time [ Time Frame: Weeks 0, 14, 26, 52, and 104 ] [ Designated as safety issue: No ]
- Insulin Use in Units Per Kilogram Body Weight Per Day [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
- Hypoglycemic Events Occurring from Randomization to End of Trial [ Time Frame: Throughout the Study ] [ Designated as safety issue: Yes ]
- Glycosylated Hemoglobin (HbA1c) Levels [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
- Emergence of Anti-Alpha 1-Antitrypsin (AAT) Antibodies [ Time Frame: Throughout the Study ] [ Designated as safety issue: Yes ]
- Frequency and Severity of All Adverse Events (AEs) [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
- Changes in D-dimer Levels Indicating Alteration in Coagulant/Anticoagulant Balance [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
- Pharmacokinetic Parameters of Aralast NP [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
| Enrollment: | 0 |
| Study Start Date: | October 2010 |
| Study Completion Date: | August 2014 |
| Primary Completion Date: | August 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Aralast NP
Participants will receive Aralast NP (90mg/kg) intravenously once a week for 12 weeks.
|
Drug: Aralast NP
Participants will receive IV infusions of Aralast NP (90mg/kg) once a week for 12 weeks.
Other Names:
|
|
Placebo Comparator: Placebo
Participants will receive placebo intravenously once a week for 12 weeks.
|
Drug: Placebo
Participants will receive IV infusions of placebo once a week for 12 weeks.
Other Name: Placebo for Aralast NP
|
Detailed Description:
T1D is an autoimmune disease. This means that your immune system (the part of your body that helps fight infections) mistakenly attacks the cells that produce insulin (beta cells in the pancreas). As beta cells are destroyed by your immune cells, your ability to produce insulin is decreased. Insulin helps keep blood glucose levels normal.
Individuals with T1D who have the ability to produce some of their own insulin (even though they still need to take insulin) may be able to achieve better glucose control than people who produce no insulin at all. Better glucose control has been shown to reduce the long-term complications of diabetes. Previous research has shown that giving medicines to affect the immune system soon after type 1 diabetes is diagnosed may stop, delay or decrease the destruction of beta cells, resulting in better glucose control.
In mouse models of disease, alpha-1 proteinase inhibitors have been shown to reverse new-onset diabetes and induce a state of self-tolerance. The RETAIN clinical trial was intended to investigate the effect of Aralast NP on preserving beta cell function and slowing the progression of T1D.
Eligibility| Ages Eligible for Study: | 8 Years to 35 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosed with type 1 diabetes (T1D) within the past 100 days
- Positive for at least one diabetes-related autoantibody (anti-GAD; anti-insulin, if obtained within 10 days of the onset of insulin therapy; IA-2 antibody and/or ICA, or ZnT8)
- Peak stimulated C-peptide level greater than (>) 0.2 pmol/mL following a mixed meal tolerance test (MMTT)
Exclusion Criteria:
- Severe active disease (hepatitis, cardiac or pulmonary disease, hypertension, immunodeficiency)
- History of any bleeding or clotting factor deficiencies, or stroke
- History of vascular disease or significant vascular abnormalities
- Positive serology exposure to hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or toxoplasmosis
- Clinically active infection with Epstein-Barr virus (EBV), cytomegalovirus (CMV), or tuberculosis (TB)
- Prior or current use of oral, inhaled or intranasal glucocorticoids, or any medication known to cause a significant, ongoing change in the course of T1D or immunologic status
- Prior treatment with alpha1-antitrypsin (AAT) or hypersensitivity to AAT or human plasma-derived products
- Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin
- Current use of any medication known to influence glucose tolerance (e.g., beta-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine anti-malarial drugs, lithium, niacin)
- Females who are pregnant or lactating, or are unwilling to defer pregnancy during study participation
- Immunoglobulin A (IgA) deficiency
- Uncontrolled hypertension
- Current life-threatening malignancy
- Any condition that in the investigator's opinion may compromise study participation or may confound the interpretation of the study results
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01183455
| United States, California | |
| University of California San Diego | |
| La Jolla, California, United States, 92093 | |
| United States, Colorado | |
| Barbara Davis Center | |
| Aurora, Colorado, United States, 80045 | |
| United States, Connecticut | |
| Yale University | |
| New Haven, Connecticut, United States, 06511 | |
| United States, Georgia | |
| Atlanta Diabetes Associates | |
| Atlanta, Georgia, United States, 30309 | |
| Emory University | |
| Atlanta, Georgia, United States, 30322 | |
| United States, Iowa | |
| University of Iowa | |
| Iowa City, Iowa, United States, 52242 | |
| United States, Maryland | |
| University of Maryland Medical Center | |
| Baltimore, Maryland, United States, 21201 | |
| Calvert Memorial Hospital | |
| Prince Frederick, Maryland, United States, 20678 | |
| United States, Massachusetts | |
| Joslin Diabetes Center | |
| Boston, Massachusetts, United States, 02215 | |
| Massachusetts General Hospital | |
| Boston, Massachusetts, United States, 02114 | |
| University of Massachusetts Medical School | |
| Worchester, Massachusetts, United States, 01655 | |
| United States, New York | |
| Columbia University | |
| New York, New York, United States, 10027 | |
| United States, Ohio | |
| Nationwide Children's Hospital | |
| Columbus, Ohio, United States, 43205 | |
| United States, Pennsylvania | |
| The Children's Hospital of Philadelphia | |
| Philadephia, Pennsylvania, United States, 19104 | |
| United States, Texas | |
| Cetero Research San Antonio | |
| San Antonio, Texas, United States, 78229 | |
| Study Chair: | Gordon Weir, MD | Joslin Diabetes Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT01183455 History of Changes |
| Other Study ID Numbers: | DAIT ITN041AI Part II |
| Study First Received: | August 16, 2010 |
| Last Updated: | December 30, 2014 |
| Health Authority: | United States: Federal Government United States: Food and Drug Administration |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
|
Diabetes Mellitus, Type 1 (new-onset) T1DM (new-onset) T1D (new-onset) Diabetes, Autoimmune |
Alpha1-Proteinase Inhibitor Alpha-1 Antitrypsin AAT |
Additional relevant MeSH terms:
|
Diabetes Mellitus Diabetes Mellitus, Type 1 Autoimmune Diseases Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases |
Alpha 1-Antitrypsin Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Serine Proteinase Inhibitors Trypsin Inhibitors |
ClinicalTrials.gov processed this record on March 03, 2015