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Islet transplantation using brain-dead donors and donors after cardiac death for patients with insulin-dependent diabetes mellitus suffering from complicating hypoglycemia unawareness (Islet transplantation for insulin-dependent diabetes mellitus)

Islet transplantation using brain-dead donors and donors after cardiac death for patients with insulin-dependent diabetes mellitus suffering from complicating hypoglycemia unawareness (Islet transplantation for insulin-dependent diabetes mellitus)

Kazuhiko Nakao

July. 08, 2021

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Mar. 31, 2022

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https://jrct.mhlw.go.jp/latest-detail/jRCTa071190048

Eguchi Susumu

Nagasaki Univercity Hospital

1-7-1 Sakamoto, Nagasaki, Nagasaki, Japan

sueguchi@nagasaki-u.ac.jp

Tomohiko Adachi

Nagasaki University Hospital

1-7-1 Sakamoto, Nagasaki, Nagasaki, Japan

+81-95-819-7316

adatomo@nagasaki-u.ac.jp

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Male or female; 20 to 65 years of age.
2. Ability to 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 insulin dependence for > 5 years at the time of the registration.
5. Absent stimulated C-peptide (< 0.3ng/mL).
6. Involvement in intensive diabetes management defined as the self monitoring of glucose values no less than a mean of three times each day, averaged over each week, and the administration of three or more insulin injections each day or insulin pump therapy. Such management must have been subjected to at least 3 clinical evaluations during the previous 12 months.
7. At least one episode of severe hypoglycemia in the past 12 months defined as an event with symptoms compatible with hypoglycemia in which the subject required the assistance of another person and which was associated with either a blood glucose level < 54 mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration.
8. At least once evaluated glycemic lability status by a Clarke score, a HYPO score and a glycemic lability index (LI) score.

1. BMI > 25 kg/m2 or weight > 80 kg.
2. Insulin requirement of > 0.8 IU/kg/day or 55 U/day.
3. Mean HbA1c value of several measurements in the previous 12 months >10 %.
4. Untreated proliferative diabetic retinopathy.
5. Blood pressure: SBP > 160 mmHg or DBP > 100 mmHg.
6. Creatinine clearance < 60 mL/min (applied only to islet transplantation alone case).
7. Presence of proteinuria > 1g/day.
8. For female participants: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 3 months after discontinuation. For male participants: Intent to procreate during the duration of the study or within 3 months after discontinuation or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant, Depo-Provera, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
9. Active infection including hepatitis B, hepatitis C, HIV, or TB as determined by a positive skin test or clinical presentation, or under treatment for suspected TB. Positive tests are acceptable only if associated with a history of previous vaccination in the absence of any sign of active infection. Positive tests are otherwise not acceptable, even in the absence of any active infection at the time of evaluation.
10. Negative screen for Epstein-Barr Virus (EBV) by IgG determination.
11. Difficulty of administration for laboratory and physical tests for evaluation or regular outpatient visits.
12. Mental abnormalities to hinder medical procedure under protocol (Assessment by psychiatrists is required and final decision is made by investigators in charge).
13. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.

Both

Insulin-dependent diabetes mellitus suffering from complicating hypoglycemia unawareness

Immunosuppressant

Insulin-dependent diabetes mellitus

The proportion of subjects with HbA1c < 7.4% and who are free of severe hypoglycemic events (from day 90 to day 365) one years after the first islet cell infusion.

1. Proportion of patients with HbA1c (NGSP) < 7.4% and severe hypoglycemic unawareness disappears 2 years after the first transplantation.
2. Proportion of patients with severe hypoglycemic attack unawareness.
3. Proportion of patients with HbA1c value (NGSP) < 7.4% two years after the first transplantation.
4. Proportion of patients with HbA1c value (NGSP) < 6.9% two years after the first transplantation.
5. Percentage of patients with insulin withdrawal by 2 years after the first transplantation.

Complete

+81-75-753-4680

Nov. 11, 2019