Heparinized Islets in Clinical Islet Transplantation

This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring Islets of Langerhans, islets, heparin Read More

Inclusion Criteria

1. Male and female patients age 18 to 65 years of age.
2. Ability to understand and provide written informed consent.
3. Mentally stable and able to comply with the procedures of the study protocol.
4. 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.
5. Stimulated C-peptide < 0.3 ng/mL (0.1 nmol/L) in response to a MMTT, before first islet transplantation.

6. All subjects must have received medical treatment of their diabetes under the guidance from an experienced endocrinologist.

   If not previously transplanted the patient must also have;

7. At least one episode of severe hypoglycaemia in the past 1 year defined as an event with at least one of the following symptoms; memory loss, confusion, uncontrollable behaviour, 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 OR
8. Reduced awareness of hypoglycaemia 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:

1. Patients with prior organ transplants other than a kidney graft and/or islets.
2. Patients with body mass index (BMI) > 30.
3. Insulin requirement > 1 Unit/kg/day at screening.
4. Consistently abnormal liver function tests (> 1.5 x ULN on two consecutive measurements > 2 weeks apart), at screening.
5. Proliferative untreated diabetic retinopathy
6. Increased risk for thrombosis (ex. homozygous APC-resistance) or bleeding (INR>1.5)
7. Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin

8. Patients with increased cardiac risk defined as;

   1. unstable coronary artery disease requiring hospitalization or revascularization within 6 months prior to baseline visit
   2. chronic heart failure which required hospitalization 30 days prior to baseline visit
9. Patients with active infections, unless treatment is not judged necessary by the investigators
10. 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.
11. Patients with active peptic ulcer disease, symptomatic gallstones or portal hypertension.
12. Patients who are pregnant or breastfeeding, or who intend to become pregnant.

13. Sexually active females who are not:

    1. post-menopausal,
    2. surgically sterile, or
    3. using a highly effective method of contraception, such as: intra uterine device, oral contraceptives, implants, injectables or barrier devices combined with spermicidal gel
14. Active alcohol or substance abuse
15. Patients with evidence of high-level sensitization (PRA> 50% with flow cytometry).
16. Patients with psychological conditions that make it unsafe to undergo islet transplantation or which preclude compliance with prescribed therapy
17. HbA1c >11% (International standard) corresponding to IFCC calibration 97 mmol/mol, at screening.
18. Medical history of egg allergy
19. Patients with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo an islet transplant
20. Patients participating in or having participated in any other clinical drug studies in the past four weeks.