Alemtuzumab Induction in Islet Transplantation

This study has been completed.
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
University of Alberta
ClinicalTrials.gov Identifier:
NCT00175253
First received: September 13, 2005
Last updated: July 11, 2012
Last verified: July 2012
  Purpose

Our experience suggests that further research with alemtuzumab is attractive in islet transplantation. Therefore, in this study we propose to combine alemtuzumab induction pre-transplant, with tacrolimus and mycophenolate mofetil maintenance immunosuppression post-transplant. In the critical early phase post transplant, we anticipate that this regimen will prove to be more effective in control of autoimmunity or rejection events, and have a more desirable side-effect profile, than previously tested combinations of induction and immunosuppressive agents.


Condition Intervention Phase
Type 1 Diabetes
Drug: alemtuzumab
Procedure: islet transplant
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: Alemtuzumab Induction With Tacrolimus and MMF Maintenance Immunosuppression in Islet Transplantation

Resource links provided by NLM:


Further study details as provided by University of Alberta:

Estimated Enrollment: 12
Study Start Date: November 2005
Study Completion Date: April 2012
Detailed Description:

This trial is a single-center, prospective, open-label study in 12 Type 1 diabetic participants receiving an islet-alone transplant along with alemtuzumab induction therapy followed by combination tacrolimus and MMF maintenance immunosuppression. Participants will receive 1 to 3 infusions of pancreatic islets of sufficient quantity to attain insulin independence.

The primary objective of this protocol is to assess the safety of a treatment regimen utilizing alemtuzumab induction and a combination of tacrolimus and MMF maintenance immunosuppression 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:

  • open to Canadians only
  • participant must have had Type 1 diabetes mellitus for more than 5 years
  • diabetes must be complicated by at least 1 of the following situations that persist despite intensive insulin management efforts: (1) Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels < 3.0 mmol/L, indicated by, 2 or more episodes of severe hypoglycemia requiring third party assistance within 12 months; or (2) Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and or 2 or more hospital visits for diabetic ketoacidosis over the last 12 months.
  • Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

Exclusion Criteria:

  • Severe co-existing cardiac disease
  • Active alcohol or substance abuse, to include cigarette smoking
  • Psychiatric disorder making the subject not a suitable candidate for transplantation
  • History of non-adherence to prescribed regimens
  • Active infection including Hepatitis C, Hepatitis B, HIV, TB
  • Any history of or current malignancies except squamous or basal skin cancer
  • BMI > 28 kg/m2 at screening visit
  • Creatinine clearance < 65 mL/min/1.73 m2
  • Blood creatinine > 150 µmol/L (1.7 mg/dL)
  • Macroalbuminuria (urinary albumin excretion rate > 300 mg/24h)
  • Baseline Hb < 105g/L (<10.5 g/dL) in women, or < 130 g/L (<13 g/dL) in men
  • Baseline screening liver function tests 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 significant sensitization on PRA
  • Insulin requirement >1.0 U/kg/day
  • HbA1C >12%
  • Uncontrolled hyperlipidemia
  • 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 Celiac disease
  • Patients with Graves disease will be excluded unless previously adequately treated with radioiodine ablative therapy
  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: NCT00175253

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):
Responsible Party: University of Alberta
ClinicalTrials.gov Identifier: NCT00175253     History of Changes
Other Study ID Numbers: 5369
Study First Received: September 13, 2005
Last Updated: July 11, 2012
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
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014