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

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

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.

Study Overview

• Status: Unknown
• Conditions: Type 1 Diabetes; End Stage Renal Disease
• Intervention / Treatment: Procedure: Intraportal islet transplantation; Procedure: Kidney transplantation; Procedure: Intramuscular islet transplantation; Procedure: Intramuscular transpl with stemcells

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Nordic Network For Clinical Islet Transplantation
• Investigators: Principal Investigator: Kaija Salmela, MD PhD, Kidney Transplant Unit, Helsinki University Hospital, Helsinki, Finland

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Anticipated): January 1, 2016
• Study Completion (Anticipated): July 1, 2016

Study Registration Dates

• First Submitted: October 16, 2013
• First Submitted That Met QC Criteria: October 17, 2013
• First Posted (Estimate): October 22, 2013

Study Record Updates

• Last Update Posted (Estimate): October 6, 2015
• Last Update Submitted That Met QC Criteria: October 5, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Type 1 diabetes; transplantation; nephropathy; intramuscular; islets
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Renal Insufficiency; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 1; Kidney Failure, Chronic
• Other Study ID Numbers: SIK01