Intraportal or Intramuscular Site for Islets in Simultaneous Islet and Kidney Transplantation

Study Overview
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Brief Summary
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Islet transplantation is a promising treatment of type 1 diabetes in selected cases. Results are however hampered by a relatively low number of islets surviving the transplantation into the liver, which currently is the site for transplantation. In the present study we compare a new transplantation site (intramuscular in the arm) to the golden standard (the liver) in patients undergoing kidney transplantation from the same donor. In half of the intramuscular transplanted patients, the islets will be mixed with mesenchymal stemcells from the recipient to, possibly, improve the immunological aspects of the transplantation.

Official Title
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Open Multi-Center Randomized Study to Compare Safety and Efficacy of Islet Transplantation Using The Intraportal or Intramuscular Site in Simultaneous Islet and Kidney Transplantation

Conditions
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Type 1 Diabetes, End Stage Renal Disease

Intervention / Treatment
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* Procedure: Intraportal islet transplantation
* Procedure: Intramuscular islet transplantation
* Procedure: Intramuscular transpl with stemcells
* Procedure: Kidney transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients age 18 to 65 years of age. Ability to provide written informed consent. Mentally stable and able to comply with the procedures of the study protocol. Clinical history compatible with type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years at the time of enrolment. Absence of stimulated C-peptide <0.1 nmol/L in response to a MMTT. All subjects must have received adequate medical treatment of their diabetes under the guidance from an experienced diabetologist. All subjects must have renal failure and be eligible for renal transplantation according to local criteria. Exclusion Criteria: Patients with prior organ transplants Patients that qualify for local simultaneous pancreas-kidney transplantation program and who prefer that option Patients with body mass index BMI > 28. Insulin requirement > 1 Unit/kg/day. If the patient is on peritoneal dialysis the same limit is set when the extra carbohydrates in the dialysis fluids have been accounted for. Consistently abnormal liver function tests ( > 1.5 x the upper limit of normal on two consecutive measurements > 2 weeks apart) Unstable diabetic retinopathy Hypercoagulability disorder or coagulopathy or International normalized ratio (INR)>1.5 Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin Patients with unstable cardiovascular status Patients with active infections, unless treatment is not judged necessary by the investigators Patients with serological evidence of infection with HIV, hepatitis B (patients with serology consistent with previous vaccination and a history of vaccination are acceptable) or hepatitis C.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraportal islet transplantation<br>Subject randomized to the protocol with intraportal islet transplantation and kidney transplantation | Procedure: Intraportal islet transplantation<br> <br> Procedure: Kidney transplantation<br>* All patients will undergo kidney transplantation regardless of arm<br>|
| Experimental: Intramuscular islet transplantation<br>Subject randomized to the protocol with intramuscular islet transplantation and kidney transplantation | Procedure: Intramuscular islet transplantation<br> <br> Procedure: Kidney transplantation<br>* All patients will undergo kidney transplantation regardless of arm<br>|
| Experimental: Intramuscular transpl with stemcells<br>Subject randomized to the protocol with intramuscular islet transplantation and where islets have been incubated autologous mesenchymal stemcells. Will also receive kidney transplant | Procedure: Intramuscular transpl with stemcells<br> <br> Procedure: Kidney transplantation<br>* All patients will undergo kidney transplantation regardless of arm<br>|
| Active Comparator: Kidney transplantation only<br>Subject that only undergoes kidney transplantation | Procedure: Kidney transplantation<br>* All patients will undergo kidney transplantation regardless of arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-peptide derived from the Mixed Meal Tolerance Test (MMTT) | Percentage of patients in each study group reaching a systemic C-peptide derived from the MMTT above 0.1 nmol/L basal (fasting) and 90-min 0.3 nmol/L 75 (+/-5) and 365 days (+/-14) after kidney transplantation | 365 days (+/-14) after kidney transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 diabetes, islets, transplantation, nephropathy, intramuscular