NCT00468442

Brief Summary

Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with the immunosuppressive medications and medications to support islet survival for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.

Trial Health

57
Monitor

Trial Health Score

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

Enrollment
2

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Nov 2006

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

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

Study Start

First participant enrolled

November 1, 2006

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

May 1, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 2, 2007

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2011

Completed
Last Updated

March 21, 2016

Status Verified

February 1, 2016

Enrollment Period

4.8 years

First QC Date

May 1, 2007

Last Update Submit

February 21, 2016

Conditions

Keywords

Insulin dependenceHypoglycemiaHypoglycemia unawareness

Outcome Measures

Primary Outcomes (1)

  • Insulin independence

    75 days after a single islet transplant

Secondary Outcomes (1)

  • reduction in insulin requirements, HbA1c, MAGE, LI, HYPO score, fasting glucose, beta score, quality of life

    75 days and 1 year following first and final infusion

Study Arms (1)

Allogeneic Pancreatic Islet Cells

EXPERIMENTAL

Participants will receive up to three islet transplants and maintenance immunosuppressive therapy.

Biological: Allogeneic Pancreatic Islet CellsBiological: Antithymocyte globulinBiological: DaclizumabBiological: RituximabDrug: Sirolimus

Interventions

transplant of islet cells injected into the portal vein of the liver

Allogeneic Pancreatic Islet Cells

Immunosuppressive that selectively depletes activated T-cells and depletes resting T-cells in a dose-dependent manner.

Also known as: ATG
Allogeneic Pancreatic Islet Cells
DaclizumabBIOLOGICAL

Will replace antithymocyte globulin in all islet transplantations after the first one

Also known as: Zenapax
Allogeneic Pancreatic Islet Cells
RituximabBIOLOGICAL

Depletes transient B-cells

Also known as: Rituxan
Allogeneic Pancreatic Islet Cells

Maintenance immunosuppressive therapy

Also known as: Rapamune
Allogeneic Pancreatic Islet Cells

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Mentally stable and able to comply with study procedures
  • Clinical history compatible with type 1 diabetes with onset at less than 40 years of age, insulin dependence for at least 5 years at study entry, and a sum of age and insulin dependent diabetes duration of at least 28
  • Absent stimulated C-peptide (less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test
  • Involvement of intensive diabetes management, defined as:
  • Self-monitoring of glucose values no less than a mean of three times each day averaged over each week
  • Administration of three or more insulin injections each day or insulin pump therapy
  • Under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least three evaluations the 12 months prior to study enrollment
  • At least one episode of severe hypoglycemia in the past 12 months, defined as an event with one of the following symptoms: memory loss; confusion; uncontrollable behavior; irrational behavior; unusual difficulty in awakening; suspected seizure; seizure; loss of consciousness; or visual symptoms in which the participant was unable to treat him/herself and which was associated with either a blood glucose (BG) level \< 54 mg/dL \[3.0 mmol/L\] or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, in the past 12 months prior to study enrollment
  • Reduced awareness of hypoglycemia. More information about this criterion, including specific definition of hypoglycemia unawareness, is in the protocol.

You may not qualify if:

  • Body mass index (BMI) greater than 30 kg/m2 or weight less than or equal to 50 kg
  • Insulin requirement of more than 1.0 IU/kg/day or less than 15 U/day
  • HbA1c greater than 10%
  • Untreated proliferative diabetic retinopathy
  • Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg
  • Measured glomerular filtration rate using iohexol of less than 80 ml/min/1.73m2. More information about this criterion is in the protocol.
  • Presence or history of macroalbuminuria (greater than 300 mg/g creatinine)
  • Presence or history of panel-reactive anti-HLA antibody levels greater than 20% by flow cytometry. More information about this criterion is in the protocol.
  • Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and 4 months after study completion
  • Active infection, including hepatitis B, hepatitis C, HIV, or tuberculosis. More information about this criterion is in the protocol.
  • Negative for Epstein-Barr virus by IgG determination
  • Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within one year prior to study enrollment
  • History of malignancy except for completely resected squamous or basal cell carcinoma of the skin
  • Known active alcohol or substance abuse
  • Baseline Hgb below the lower limits of normal, lymphopenia, neutropenia, or thrombocytopenia
  • +20 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Location

Related Links

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Hypoglycemia

Interventions

Antilymphocyte SerumDaclizumabRituximabSirolimus

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Immune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex MixturesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodies, Monoclonal, Murine-DerivedMacrolidesLactonesOrganic Chemicals

Study Officials

  • Ali Naji, MD, PhD

    University of Pennsylvania

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 1, 2007

First Posted

May 2, 2007

Study Start

November 1, 2006

Primary Completion

September 1, 2011

Study Completion

September 1, 2011

Last Updated

March 21, 2016

Record last verified: 2016-02

Locations