Extended Follow-Up After Islet Transplantation in T1D

Study Overview
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Brief Summary
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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
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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)

Official Title
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Extended Follow-Up After Islet Transplantation in Type 1 Diabetes (CIT-08)

Conditions
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Type 1 Diabetes (T1D), Islet Transplantation

Intervention / Treatment
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* Drug: Maintenance Immunosuppressive Treatment


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CIT Islet Transplantation Recipients<br>Subjects who received an islet-cell transplant for Type 1 Diabetes (T1D) while enrolled in one of the Clinical Islet Transplantation (CIT) parent studies and continue to have islet graft function. All subjects will continue immunosuppressive medications under CIT08. Detailed follow-up evaluations including but not limited to islet function will occur on an annual basis. The immunosuppressive medications (e.g., tacrolimus, sirolimus, cyclosporine, mycophenolate mofetil [MMF], mycophenolic sodium) in this study are obtained by prescription unless provided by the study through the drug distributor. Generic brands are allowed, when available. Antibacterial, antifungal, and antiviral prophylaxis, insulin therapy, and other standard therapies will be provided per site-specific practices. | Drug: Maintenance Immunosuppressive Treatment<br>* 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.<br>* Other names: Myfortic®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of sustained islet allograft function | 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 | Month 36,48,60,72,84,96,108,120,132 and 144 status post last islet transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum creatinine and calculated eGFR at each annual study visit | Measured as part of each annual follow-up evaluation | Month 36,48,60,72,84,96,108,120,132 and 144 status post last islet transplant | 
| Incidence of serious adverse events (SAEs) during the 12-month period preceding each annual study visit | Insulin usage will be estimated from the one-week self report values | Month 36,48,60,72,84,96,108,120,132 and 144 status post last islet transplant | 
| Insulin requirements during a one-week period preceding each annual study visit | Insulin usage will be estimated from the one-week self report values | Month 36,48,60,72,84,96,108,120,132 and 144 status post last islet transplant | 
| Incidence of severe hypoglycemic events during the 12-month period preceding each annual study visit | 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. | 36 months, 48 months, 60 months, 72 months, 84 months, 96 months, 108 months, 120 months, 132 months and 144 months | 
| HbA1c levels at each annual study visit | Glycosylated hemoglobin test determination during each follow-up visit | Month 36,48,60,72,84,96,108,120,132 and 144 status post last islet transplant | 
| Incidence of all-cause mortality |  | By month 144 status post last islet transplant | 
| Donor-specific alloantibodies | 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. | By month 144 status post last islet transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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islet allograft function, c-peptide production, maintenance immunosuppressive medications