Islet Transplantation, Type 1 Diabetes (T1D)
Conditions
Keywords
islet allograft function, c-peptide production, maintenance immunosuppressive medications
Brief summary
The purpose of this study is to provide patients who have received at least one islet transplant as a previous participant in a Clinical Islet Transplantation Consortium (CIT) clinical trial with maintenance immunosuppressive medications and to collect information about the safety of the medications and islet function.
Detailed description
After islet-cell transplantation in the CIT studies\*, each subject receives maintenance immunosuppressive medications. The purpose of this protocol is to collect additional follow-up for safety and efficacy from CIT subjects with graft function after their completion in their CIT parent study. It is expected that most subjects will retain measurable islet function and, in the islet-alone studies, continue to receive immunosuppressive medications at the time of completing their CIT parent study. \*CIT parent studies: CIT02 (NCT00464555), CIT03 (NCT00434850), CIT04 (NCT00468403), CIT05 (NCT00468442), CIT06 (NCT00468117), and CIT07 (NCT00434811)
Interventions
DRUGMaintenance Immunosuppressive Treatment
All immunosuppressive and immunomodulatory therapies are used presently to prevent rejection of transplanted islet cells. The agents listed are those used in the parent trials and continued in this trial, CIT08.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Clinical Islet Transplantation Consortium
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who have received an islet transplant during participation in the following Clinical Islet Transplantation (CIT) parent studies: CIT02 (NCT00464555), CIT03 (NCT00434850), CIT04 (NCT00468403), CIT05 (NCT00468442), CIT06 (NCT00468117), and CIT07 (NCT00434811) * A functioning pancreatic islet graft (e.g., absence of graft failure as defined in parent study) requiring immunosuppression * Willingness of participants to continue to use an approved method of contraception during and 4 months after study participation * Ability to provide written informed consent * Resident of the United States of America * Documentation of the existence or lack of health insurance coverage and whether immunosuppressants are covered.
Exclusion criteria
* For female subjects-Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation * For male subjects-Intent to procreate during the duration of the study or within 4 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. * Received an islet transplant in a non-CIT research study * Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of sustained islet allograft function | Month 36,48,60,72,84,96,108,120,132 and 144 status post last islet transplant | A C-peptide \>/= 0.3 ng/mL at 0, 60, or 90 minutes after a Mixed-Meal Tolerance Test (MMTT) will be considered evidence of insulin production by transplanted islets |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of serious adverse events (SAEs) during the 12-month period preceding each annual study visit | Month 36,48,60,72,84,96,108,120,132 and 144 status post last islet transplant | Insulin usage will be estimated from the one-week self report values |
| Insulin requirements during a one-week period preceding each annual study visit | Month 36,48,60,72,84,96,108,120,132 and 144 status post last islet transplant | Insulin usage will be estimated from the one-week self report values |
| Incidence of severe hypoglycemic events during the 12-month period preceding each annual study visit | 36 months, 48 months, 60 months, 72 months, 84 months, 96 months, 108 months, 120 months, 132 months and 144 months | Numbers of severe hypoglycemic events will be estimated from the self report values obtained at each follow-up visit. Defined as an event with one of the following symptoms: memory loss; confusion; uncontrollable behavior; irrational behavior; unusual difficulty in awakening; suspected seizure; 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 glucose level \<54 mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, IV glucose, or glucagon administration. |
| Serum creatinine and calculated eGFR at each annual study visit | Month 36,48,60,72,84,96,108,120,132 and 144 status post last islet transplant | Measured as part of each annual follow-up evaluation |
| Incidence of all-cause mortality | By month 144 status post last islet transplant | — |
| Donor-specific alloantibodies | By month 144 status post last islet transplant | Subjects with confirmed graft failure will continue with annual study visits; however, metabolic assessments should not be completed. Subjects who were enrolled in islet-alone parent studies and who experience graft failure and subsequently stop immunosuppression will have alloantibody assessed 3 months after their last dose of immunosuppression. |
| HbA1c levels at each annual study visit | Month 36,48,60,72,84,96,108,120,132 and 144 status post last islet transplant | Glycosylated hemoglobin test determination during each follow-up visit |
Countries
United States
Outcome results
None listed