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Trial record 1 of 1 for:    NCT00965458
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Inducing Remission in Type 1 Diabetes With Alefacept (T1DAL)

This study has been completed.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00965458
First received: August 22, 2009
Last updated: August 12, 2014
Last verified: August 2014
  Purpose

The purpose of this trial is to test whether a drug called alefacept will slow or halt destruction of the beta cells in the pancreas. If the destruction of the beta cells is stopped, the patients might be able to produce insulin on their own longer, which could stop or slow the progression of their type 1 diabetes.

This is a multi-center prospective, placebo-controlled, double-blind and randomized trial to investigate the ability of alefacept to protect residual beta cells from ongoing autoimmune destruction in adolescents and young adults with newly diagnosed Type 1 Diabetes Mellitus (T1DM).


Condition Intervention Phase
New-onset Type 1 Diabetes Mellitus
Biological: Alefacept
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: Inducing Remission in New Onset Type 1 Diabetes Mellitus With Alefacept (Amevive®)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) [ Time Frame: Baseline (pre-treatment initiation), Week 52 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) [ Time Frame: Baseline (Pre-treatment initiation), Week 52, and Week 104 ] [ Designated as safety issue: No ]
  • 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) [ Time Frame: Baseline (Pre-treatment initiation), Week 52, and Week 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 ]
  • Major Hypoglycemic Events Occurring From Randomization [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
  • Hemoglobin A1c [ Time Frame: Week 52, Week 104 ] [ Designated as safety issue: No ]
  • Rate of Injection Reactions; Defined as Fever, Chills, Headache, Nausea, Vomiting, and Injection-site Pain in Participants Receiving Alefacept or Placebo. [ Time Frame: Initiation of treatment through duration of study participation ] [ Designated as safety issue: Yes ]
  • Rate of Hypersensitivity Reactions; Defined as Signs and Symptoms of Anaphylaxis, Wheezing, Dyspnea, Urticaria, and Hypotension in Participants Receiving Alefacept or Placebo [ Time Frame: Initiation of treatment through duration of study participation ] [ Designated as safety issue: Yes ]
  • Rate of Evidence of Infection with Epstein-Barr virus (EBV), Cytomegalovirus (CMV), or Tuberculosis (TB) in Participants Receiving Alefacept or Placebo [ Time Frame: Initiation of treatment through duration of study participation ] [ Designated as safety issue: Yes ]
  • Frequency and Severity of all Adverse Events (AEs) in Participants Receiving Alefacept or Placebo [ Time Frame: Initiation of treatment through duration of study participation ] [ Designated as safety issue: Yes ]

Enrollment: 49
Study Start Date: March 2011
Study Completion Date: April 2014
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alefacept
Subjects in this group receive weekly intramuscular injections of alefacept (15 mg) for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.
Biological: Alefacept
Weekly intramuscular injections of alefacept (15 mg) for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.
Other Name: Amevive®
Placebo Comparator: Placebo
Subjects in this group received weekly intramuscular injections of a placebo saline solution of equal volume to the alefacept group for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.
Drug: Placebo
Weekly intramuscular injections of a placebo saline solution of equal volume to the alefacept group for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.
Other Name: Inactive drug (pharmacologically)

Detailed Description:

T1DM is an autoimmune disease that can emerge suddenly, causing dependence on insulin for life. This means that the immune system (the part of your body that helps fight infections) mistakenly attacks the cells in the pancreas that produce insulin (beta cells). As beta cells are destroyed, one's ability to produce insulin is decreased. Insulin helps keep blood glucose (sugar) levels normal.

For a period right after diagnosis, the pancreas is still able to make small amounts of insulin. Individuals with diabetes who have the ability to produce some of their own insulin may be able to achieve better blood sugar control than people who produce no insulin at all. Based on previous research, doctors think that giving medicines to affect the immune system soon after diagnosis may stop, delay, or decrease the destruction of beta cells, resulting in better glucose control. This can help prevent secondary complications of diabetes down the road.

Research has improved the outlook for T1DM over the last decade. Doctors are investigating, for example, how to save insulin-producing cells and extend the honeymoon period as long as possible.

Despite progress towards understanding the science behind T1DM, there remains a significant need to investigate alternative approaches to this disease in order to bring about long-term remission. For this reason, scientists are working hard to develop new treatments that can be given soon after diagnosis to preserve the remaining beta cells.

Currently there is no cure for T1DM; however, with new investigational medications and innovative clinical research studies, such as T1DAL, a new approach towards managing T1DM may be on the horizon.

Enrollees will receive weekly intramuscular injections of alefacept or placebo for two 12 week periods, with a 12-week pause between treatment intervals. This schedule or drug dosing may be altered due to the needs of the subject or at the discretion of the physician investigator.

  Eligibility

Ages Eligible for Study:   12 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recent diagnosis (within 100 days of enrollment) of T1DM
  • Positive for at least one diabetes autoantibody (Glutamate decarboxylase [GAD-65GAD65], IA2, ZnT8, ICA and Insulin, if obtained within 10 days of the onset of exogenous insulin therapy)
  • Peak stimulated C-peptide level > 0.2 pmol/mL following a mixed-meal tolerance test (MMTT)
  • Willingness to provide written informed consent (either the subject or the subject's legally authorized representative)

Exclusion Criteria:

  • Severe reaction or anaphylaxis to human monoclonal antibodies
  • History of malignancy or significant cardiovascular disease (including history of myocardial infarction, angina, use of anti-anginal medicines (e.g., nitroglycerin), or abnormal stress test)
  • History of recent or ongoing uncontrolled bacterial, viral, fungal, or other opportunistic infections
  • Evidence of infection with hepatitis B virus (HBV) as defined by hepatitis B surface antigen, HBsAg; hepatitis C virus (HCV) defined by anti-HCV antibodies; human immunodeficiency virus (HIV); or toxoplasmosis
  • Positive tuberculin skin test (PPD)
  • Clinically active infection with Epstein-Barr virus (EBV)-EBV viral load ≥ 10,000 copies per 10^6 PBMCs; cytomegalovirus (CMV) -CMV viral load ≥10,000 copies per mL whole blood; or tuberculosis (TB)
  • Diagnosis of liver disease or hepatic enzymes, as defined by ALT and/or AST ≥ 2 times the upper limit of normal
  • Prior or current treatment that is known to cause a significant, ongoing change in the course of T1DM or immunologic status, including high-dose inhaled, extensive topical or systemic glucocorticoids
  • 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., atypical antipsychotics, diphenylhydantoin, thiazide, or other potassium-depleting diuretics, β-adrenergic blockers, niacin)
  • Any of the following hematologic abnormalities, confirmed by repeat tests at least 1 week apart:

    1. White blood count <4000/μL or >14,000/μL;
    2. CD4+ count below the lower limit of normal;
    3. Platelet count <150,000 /μL; or
    4. Hemoglobin <10 g/dL.
  • Females who are pregnant, lactating, or planning on pregnancy during the 2-year study period
  • History of bone marrow transplantation, or autoimmune disease associated with lymphopenia
  • Any medical condition that in the opinion of the principal investigator would interfere with safe completion of the trial
  • Prior participation in a clinical trial that could potentially affect T1DM or immunologic status
  • Receipt of a live vaccine (e.g., varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, bacillus Calmette-Guérin, and smallpox) in the 6 weeks before enrollment
  • Participation in an investigational clinical trial within the last six weeks
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00965458

Locations
United States, Arizona
University of Arizona
Tuscon, Arizona, United States, 85724
United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
University of California - San Francisco
San Francisco, California, United States, 94143
United States, Colorado
Barbara Davis Center for Childhood Diabetes - University of Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Hospital & Clinics
Iowa City, Iowa, United States, 52242
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Missouri
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States, 64108
United States, Nebraska
Creighton University
Omaha, Nebraska, United States, 68131
United States, North Carolina
University of North Carolina
Durham, North Carolina, United States, 27713
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Washington
Benaroya Research Institute at Virginia Mason
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Immune Tolerance Network (ITN)
Investigators
Principal Investigator: Mark R Rigby, MD, PhD Indiana University
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00965458     History of Changes
Other Study ID Numbers: DAIT ITN045AI
Study First Received: August 22, 2009
Last Updated: August 12, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
New-onset Type 1 Diabetes Mellitus
New-onset T1DM
New-onset T1D
Alefacept
Amevive®

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Alefacept
Dermatologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014