Alemtuzumab Induction in Islet Transplantation

Type 1 Diabetes Clinical Trial

Official title:

Alemtuzumab Induction With Tacrolimus and MMF Maintenance Immunosuppression in Islet Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00175253
• Other study ID #: 5369
• Status: Completed
• Phase: Phase 2
• First received: September 13, 2005
• Last updated: July 11, 2012
• Start date: November 2005
• Est. completion date: April 2012

Study information

• Verified date: July 2012
• Source: University of Alberta
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Type 1 Diabetes

Intervention

Drug:
• alemtuzumab

Procedure:
• islet transplant

Locations

Country	Name	City	State
Canada	University of Alberta - Clinical Islet Transplant Program	Edmonton	Alberta

Sponsors (2)

Lead Sponsor	Collaborator
University of Alberta	Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

Canada,