Islet Transplantation Using Campath-1H and Infliximab Induction

This study has been completed.
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by:
University of Alberta
ClinicalTrials.gov Identifier:
NCT00175266
First received: September 12, 2005
Last updated: October 1, 2009
Last verified: October 2009
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes
Drug: alemtuzumab
Procedure: islet transplant
Drug: infliximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Islet Transplantation in Type 1 Diabetic Patients Using Campath-1H and Infliximab Induction

Resource links provided by NLM:


Further study details as provided by University of Alberta:

Estimated Enrollment: 12
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00175266

Locations
Canada, Alberta
University of Alberta - Clinical Islet Transplant Program
Edmonton, Alberta, Canada, T6G2C8
Sponsors and Collaborators
University of Alberta
Juvenile Diabetes Research Foundation
Investigators
Principal Investigator: A.M. James Shapiro, MD, PhD University of Alberta
  More Information

No publications provided by University of Alberta

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00175266     History of Changes
Other Study ID Numbers: 3516
Study First Received: September 12, 2005
Last Updated: October 1, 2009
Health Authority: Canada: Health Canada

Keywords provided by University of Alberta:
islet
transplantation

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Alemtuzumab
Infliximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014