NCT00285194

Brief Summary

The collective effects of two-layer pancreas preservation, pretransplant islet culture, day -2 pretransplant immunosuppression, and induction immunosuppression with the FcR-nonbinding anti-CD3 monoclonal antibody hOKT3γ1 (Ala-Ala)to facilitate diabetes reversal after single-donor islet transplantation.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Apr 2000

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

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

April 1, 2000

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2004

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2004

Completed
2.1 years until next milestone

First Submitted

Initial submission to the registry

January 30, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 1, 2006

Completed
Last Updated

August 2, 2012

Status Verified

July 1, 2012

Enrollment Period

3.8 years

First QC Date

January 30, 2006

Last Update Submit

July 31, 2012

Conditions

Type 1 DiabetesHypoglycemia

Outcome Measures

Primary Outcomes (7)

  • Safety, tolerability, immune activity, and pharmacokinetics of hOKT3γ1 (Ala-Ala) antibody induction therapy for the prevention of autoimmune destruction and rejection of allogeneic islet transplants as measured by:

  • -Physical examination

  • -Vital signs

  • -Body weight

  • -Adverse events

  • -Laboratory and diagnostic safety assessments included complete blood counts with differential and platelets, circulating T cell phenotypes, and serum chemistry.

  • -Immune activity and pharmacokinetic assessments included hOKT3γ1 (Ala-Ala) level and half-life, monoclonal antibody coating and modulation of CD3 on peripheral blood T cells, and anti-hOKT3γ1 (Ala-Ala) antibody responses.

Secondary Outcomes (4)

  • Efficacy of hOKT3γ1 (Ala-Ala) antibody induction therapy for the prevention of autoimmune destruction and rejection of islet transplants as defined by:

  • -Proportion of subjects with full islet graft function (insulin independence and HbA1c <7%);

  • -Proportion of subjects with partial islet graft function (insulin dependence, basal or arginine-stimulated C-peptide levels of greater or equal to 0.5 ng/ml and HbA1c <7%);

  • -Proportion of subjects with slet graft loss will be defined as a return to insulin therapy for >30 days, absence of basal and arginine-stimulated C-peptide, re-transplantation, or patient death;

Interventions

Allogeneic Islets of LangerhansDRUG
hOKT3γ1 (Ala-Ala)DRUG

Eligibility Criteria

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

You may qualify if:

  • Primary islet allotransplant
  • Type 1 diabetes mellitus, complicated by at least one of the following situations that persist despite intensive efforts in close cooperation with their diabetes care team:
  • Metabolic lability/instability;
  • Reduced awareness of hypoglycemia;
  • Persistently poor glucose control (as defined by HgbA1c\>10% at the end of six months of intensive management efforts with the diabetes care team);
  • Progressive secondary complications.
  • Age 18 and older
  • Able to give written informed consent

You may not qualify if:

  • Age less than 18 years
  • Body weight greater than75 kg.
  • BMI greater than 26 kg/m2 for male and females
  • Waist-to-hip ratio 0.80 (female) and 0.95 (male)
  • First degree relative with type 2 diabetes
  • Insulin requirement of greater than 0.7 IU/kg/day
  • HbA1C greater than 12%
  • Positive C-peptide response to intravenous arginine stimulation
  • Untreated proliferative retinopathy
  • Macroalbuminuria (urinary albumin excretion greater than 300 mg/24hrs)
  • Creatinine clearance greater than 85 ml/min/1.73 m2 in females, greater than 95 ml/min/1.73 m2 in males
  • Serum creatinine greater than 1.2 mg/dl
  • Previous pancreas or islet transplant
  • Previous OKT3 antibody therapy
  • Presence of history of panel-reactive anti-HLA antibodies greater than 10%
  • +23 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Universtiy of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

  • Hering BJ, Kandaswamy R, Harmon JV, Ansite JD, Clemmings SM, Sakai T, Paraskevas S, Eckman PM, Sageshima J, Nakano M, Sawada T, Matsumoto I, Zhang HJ, Sutherland DE, Bluestone JA. Transplantation of cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody. Am J Transplant. 2004 Mar;4(3):390-401. doi: 10.1046/j.1600-6143.2003.00351.x.

    PMID: 14961992RESULT

Related Links

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Hypoglycemia

Interventions

alanylalanine

Condition Hierarchy (Ancestors)

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

Study Officials

  • Bernhard J. Hering, M.D.

    University of Minnesota

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 30, 2006

First Posted

February 1, 2006

Study Start

April 1, 2000

Primary Completion

January 1, 2004

Study Completion

January 1, 2004

Last Updated

August 2, 2012

Record last verified: 2012-07

Locations

US(1)