Trial record 12 of 37 for:    Islets of Langerhans Transplantation | Open Studies

Heparinized Islets in Clinical Islet Transplantation

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Corline Systems AB.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
Corline Systems AB
ClinicalTrials.gov Identifier:
NCT00678990
First received: May 14, 2008
Last updated: June 7, 2011
Last verified: June 2011
  Purpose

In this study the islets will be surface modified to carry immobilised heparin (Corline Heparin Surface) prior to transplantation. The primary objective is to protect the islets from being attacked by the immediate defence systems in blood (coagulation and inflammation), so that a larger portion of the islets will survive the initial phase and engraft. Evaluation will be based on metabolic and blood chemistry parameters, and in some patients also by radioactive labelling of islets and imaging by PET.


Condition Intervention
Islet Transplantation
Procedure: Transplantation of islets with heparin coating

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: Open Study to Evaluate Safety and Efficacy of Allogenic Islet Transplantation Using Islets Coated With Immobilised Heparin

Resource links provided by NLM:


Further study details as provided by Corline Systems AB:

Estimated Enrollment: 10
Detailed Description:

Transplantation of islets of Langerhans isolated from donated organs is a promising therapy for diabetes type 1. The results so far have, however, not met with the expectations due to relatively low efficiency. Even in situations where the patients have become insulin-free, it has been estimated that the transplanted islet mass is less than 25% of the islet mass of a healthy individual, which in many cases has required repeated use of insulin injections. The islets are transferred to the patient by an infusion drop to the liver via the portal vein.

Researches within the Nordic Network for Clinical Islet Transplantation have in a series of publications shown that the islets are subject to a violent immunological reaction that is non-specific with regard to the individual patient (IBMIR) during the initial contact with blood (Moberg et al, Lancet 2002, among several). The IBMIR reaction is in the earliest phase mediated by coagulation and complement reactions.

In this study the islets will be surface modified to carry immobilised heparin (Corline Heparin Surface) prior to transplantation. The primary objective is to protect the islets from being attacked by IBMIR so that a larger portion of the islets will survive the initial phase and engraft. In a recent paper published by the research group (Cabric et. al., Diabetes, May 2007), the beneficial effects of immobilised heparin on the islets to counteract IBMIR were shown by experiments at the lab bench and in experimental animals.

The evaluation of the transplantations in this study will be based on metabolic and blood chemistry parameters, similar to the evaluations of other transplanted patients within the Nordic Network. A limited subgroup of patients will be evaluated by means of radioactive labelling of a portion of the transplanted islets allowing for investigation with PET (positron emission tomography). By this method it is possible to show the distribution of islets in the liver and to assess how the islets will survive the first hours after the infusion (Eich et.al., New England Journal of Medicine, June 28, 2007).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must meet all of the following criteria to be considered eligible for participation in the study

  • 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.

If not previously kidney transplanted the patient must also have;

  • At least one episode of severe hypoglycemia in the past 1 year defined as an event with at least one of the following symptoms; memory loss, confusion, uncontrollable behavior, unusual difficulty in awakening, suspected seizure, loss of consciousness, or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood/plasma glucose level < 54 mg/dl [3.0 mmol/L] or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration

and

  • Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more.

Exclusion Criteria:

Patients who meet any of these criteria are not eligible for participation in the study:

  • Patients with prior organ transplants other than a well functioning kidney graft
  • Patients with body mass index (BMI) > 30.
  • Insulin requirement > 1 Unit/kg/day.
  • 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 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.
  • Patients with active peptic ulcer disease, symptomatic gallstones or portal hypertension.
  • Patients who are pregnant or breastfeeding, or who intend to become pregnant.
  • Sexually-active females who are not: a) post-menopausal, b) surgically sterile, or c) using an acceptable method of contraception: oral contraceptives, Norplant, Depo-Provera, and barrier devices combined with spermicidal gel are acceptable; condoms used alone are not acceptable
  • Active alcohol or substance abuse
  • Patients with evidence of high-level sensitization (PRA> 20%).
  • Patients with psychological conditions that make it unsafe to undergo islet transplantation or which preclude compliance with prescribed therapy
  • Activated Protein C Resistance (APC-R)
  • HbA1c >10% (Swedish standard).
  • Allergy to eggs
  • Antibodies against Avidin
  • Patients with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo an islet transplant
  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: NCT00678990

Contacts
Contact: Gunnar Tufveson, Professor +46 18 6113116 gunnar.tufveson@akademiska.se

Locations
Sweden
Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital Not yet recruiting
Göteborg, Sweden, SE-413 45
Contact: Marie Felldin, MD    +46 31 3427019    marie.felldin@surgery.gu.se   
Principal Investigator: Marie Felldin, MD         
Department of Nephrology and Transplantation, University Hospital MAS Not yet recruiting
Malmö, Sweden, SE-205 02
Contact: Helene Andersson, MD    +46 40 331000    helene.h.andersson@skane.se   
Principal Investigator: Helene Andersson, MD         
Department of Transplantation Surgery, Karolinska University Hospital Not yet recruiting
Stockholm, Sweden, SE-141 86
Contact: Torbjörn Lundgren, MD    +46 73 6994946    torbjorn.lundgren@karolinska.se   
Principal Investigator: Annika Tibell, Assoc. Prof.         
Sub-Investigator: Torbjörn Lundgren, MD         
Department of Transplantation and Liver Surgery, Uppsala University Hospital Not yet recruiting
Uppsala, Sweden, SE-751 85
Contact: Gunnar Tufveson, Professor    +46 18 6113116    gunnar.tufveson@akademiska.se   
Principal Investigator: Gunnar Tufveson, Professor         
Sponsors and Collaborators
Corline Systems AB
Investigators
Principal Investigator: Gunnar Tufveson, Professor Uppsala University Hospital
  More Information

No publications provided

Responsible Party: Professor Gunnar Tufveson, Department of Transplantation and Liver Surgery
ClinicalTrials.gov Identifier: NCT00678990     History of Changes
Other Study ID Numbers: SAL-01
Study First Received: May 14, 2008
Last Updated: June 7, 2011
Health Authority: Sweden: Medical Products Agency

Keywords provided by Corline Systems AB:
Islets of Langerhans
islets
heparin

Additional relevant MeSH terms:
Calcium heparin
Heparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 26, 2014