NCT01183455

Brief Summary

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Oct 2010

Typical duration for phase_2

Geographic Reach
1 country

15 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 16, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 17, 2010

Completed
2 months until next milestone

Study Start

First participant enrolled

October 1, 2010

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2014

Completed
Last Updated

December 31, 2014

Status Verified

December 1, 2014

Enrollment Period

3.8 years

First QC Date

August 16, 2010

Last Update Submit

December 30, 2014

Conditions

Keywords

Diabetes Mellitus, Type 1 (new-onset)T1DM (new-onset)T1D (new-onset)Diabetes, AutoimmuneAlpha1-Proteinase InhibitorAlpha-1 AntitrypsinAAT

Outcome Measures

Primary Outcomes (1)

  • Mixed-Meal Tolerance Test (MMTT)-Stimulated 2-hour C-peptide Area Under the Curve (AUC)

    Week 52

Secondary Outcomes (9)

  • MMTT-Stimulated Peak and 4-hour C-peptide AUC

    Weeks 52 and 104

  • MMTT-Stimulated 2-hour C-Peptide AUC Assessed Over Time

    Weeks 0, 14, 26, 52, and 104

  • Insulin Use in Units Per Kilogram Body Weight Per Day

    Weeks 52 and 104

  • Hypoglycemic Events Occurring from Randomization to End of Trial

    Throughout the Study

  • Glycosylated Hemoglobin (HbA1c) Levels

    Weeks 52 and 104

  • +4 more secondary outcomes

Study Arms (2)

Aralast NP

EXPERIMENTAL

Participants will receive Aralast NP (90mg/kg) intravenously once a week for 12 weeks.

Drug: Aralast NP

Placebo

PLACEBO COMPARATOR

Participants will receive placebo intravenously once a week for 12 weeks.

Drug: Placebo

Interventions

Participants will receive IV infusions of Aralast NP (90mg/kg) once a week for 12 weeks.

Also known as: Alpha 1-Proteinase Inhibitor Human, Alpha,-antitrypsin, AAT
Aralast NP

Participants will receive IV infusions of placebo once a week for 12 weeks.

Also known as: Placebo for Aralast NP
Placebo

Eligibility Criteria

Age8 Years - 35 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

University of California San Diego

La Jolla, California, 92093, United States

Location

Barbara Davis Center

Aurora, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

Atlanta Diabetes Associates

Atlanta, Georgia, 30309, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Calvert Memorial Hospital

Prince Frederick, Maryland, 20678, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

University of Massachusetts Medical School

Worchester, Massachusetts, 01655, United States

Location

Columbia University

New York, New York, 10027, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

The Children's Hospital of Philadelphia

Philadephia, Pennsylvania, 19104, United States

Location

Cetero Research San Antonio

San Antonio, Texas, 78229, United States

Location

Related Links

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Diabetes Mellitusalpha 1-Antitrypsin Deficiency

Interventions

alpha 1-Antitrypsin

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System DiseasesLiver DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesSubcutaneous EmphysemaEmphysemaPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

GlycoproteinsGlycoconjugatesCarbohydratesSerpinsPeptidesAmino Acids, Peptides, and ProteinsAcute-Phase ProteinsBlood ProteinsProteinsAlpha-GlobulinsSerum GlobulinsGlobulins

Study Officials

  • Gordon Weir, MD

    Joslin Diabetes Center

    STUDY CHAIR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 16, 2010

First Posted

August 17, 2010

Study Start

October 1, 2010

Primary Completion

August 1, 2014

Study Completion

August 1, 2014

Last Updated

December 31, 2014

Record last verified: 2014-12

Locations