Islet Transplantation Using Campath-1H and Infliximab Induction

University of Alberta

Status and phase

Completed

Phase 2

Conditions

Type 1 Diabetes

Treatments

Drug: infliximab

Drug: alemtuzumab

Procedure: islet transplant

Study type

Interventional

Funder types

Other

Identifiers

NCT00175266

3516

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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