Islet Transplantation Using Campath-1H and Infliximab Induction

October 1, 2009 updated by: University of Alberta

Islet Transplantation in Type 1 Diabetic Patients Using Campath-1H and Infliximab Induction

Islet transplantation has been investigated as a treatment for Type 1 diabetes mellitus in selected patients with inadequate glucose control despite insulin therapy. However, the perennial hope that such an approach would result in long-term freedom from the need for exogenous insulin, with stabilization of the secondary complications of diabetes, has failed to materialize in practice. The goal of the present study is therefore to improve the safety and efficacy of clinical islet-alone transplantation by minimizing dependence on calcineurin-inhibitor therapy - thereby avoiding potential nephrotoxicity, and furthermore improving success with single-donor islet infusions by avoiding all diabetogenic immunosuppression. Campath-1H, combined with Infliximab induction therapy provides a unique opportunity to minimize dosing of maintenance long-term immunosuppression while further promoting islet engraftment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a single-centre, prospective, open-label study in Type 1 diabetic participants receiving an islet cell transplant; all participants will receive Campath-1H + Infliximab induction therapy followed by sirolimus and ultra-low dose tacrolimus maintenance therapy.

The primary objective of this protocol is to assess the safety of this treatment regimen in adult Type 1 diabetic participants receiving their first islet transplant.

Study Type

Interventional

Enrollment

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G2C8
        • University of Alberta - Clinical Islet Transplant Program

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • must have Type 1 diabetes mellitus for more than 5 years
  • diabetes must be complicated by at least one of the following situations that persist despite intensive insulin management efforts. The complicating situations are (1) Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels of < 3.0 mmol/L; (2) Metabolic lability/instability, characterized by MAGE ≥ 11.0 mmol/L and wide swings in blood glucose despite optimal diabetes therapy; and (3) Despite efforts at optimal glucose control, progressive secondary complications of diabetes, including retinopathy, neuropathy, or nephropathy

Exclusion Criteria:

  • Severe co-existing cardiac disease
  • Active alcohol or substance abuse
  • Psychiatric disorder making the subject not a suitable candidate for transplantation
  • Active infection including hepatitis C, hepatitis B, HIV, or TB
  • Any history of or current malignancies except squamous or basal skin cancer
  • BMI > 28 kg/m2 or body weight > 85 kg at screening visit
  • Positive fasting C-peptide response on assessment (2 positive results)
  • Creatinine clearance < 80 mL/min/1.73 m2
  • Serum creatinine > 150 µmol/L
  • Macroalbuminuria (urinary albumin excretion rate > 300 mg/24h)
  • Baseline Hb < 105g/L in women, or < 130 g/L in men
  • Baseline LFT's outside of normal range
  • Untreated proliferative retinopathy
  • Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast feeding
  • Previous transplant, or evidence of sensitization on PRA
  • Insulin requirement > 1.0 IU/kg/day
  • HbA1C > 0.12
  • Hyperlipidemia (fasting LDL cholesterol > 3.4 mmol/L, treated or untreated; and/or fasting triglycerides > 2.3 mmol/L)
  • Under treatment for a medical condition requiring chronic use of steroids
  • Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT INR > 1.5
  • Untreated Addison's disease
  • Untreated Celiac disease
  • Untreated thyroid disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alberta

Collaborators

Juvenile Diabetes Research Foundation

Investigators

  • Principal Investigator: A.M. James Shapiro, MD, PhD, University of Alberta

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 15, 2005

Study Record Updates

Last Update Posted (Estimate)

October 2, 2009

Last Update Submitted That Met QC Criteria

October 1, 2009

Last Verified

October 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3516

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Type 1 Diabetes

Clinical Trials on infliximab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jamaica

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe