Extended Follow-Up After Islet Transplantation in T1D

• ClinicalTrials.gov Identifier: NCT01369082
• Recruitment Status: Completed
• First Posted: June 8, 2011
• Last Update Posted: November 9, 2017
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Clinical Islet Transplantation Consortium
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

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.

Condition or disease	Intervention/treatment
Type 1 Diabetes (T1D); Islet Transplantation	Drug: Maintenance Immunosuppressive Treatment

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)

Study Design

• Study Type: Observational
• Actual Enrollment: 75 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Extended Follow-Up After Islet Transplantation in Type 1 Diabetes (CIT-08)
• Study Start Date: May 2011
• Actual Primary Completion Date: July 2017
• Actual Study Completion Date: July 2017

Groups and Cohorts

Group/Cohort

Intervention/treatment

CIT Islet Transplantation Recipients; 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; 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.; Other Names: tacrolimus; Prograf®; FK506; sirolimus; rapamycin; Rapamune®; cyclosporine; Neoral®; mycophenolate mofetil (MMF); CellCept®; mycophenolic sodium; Myfortic®

Outcome Measures

Primary Outcome Measures :

1. Duration of sustained islet allograft function [ Time Frame: 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 Outcome Measures :

1. Serum creatinine and calculated eGFR at each annual study visit [ Time Frame: 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
2. Incidence of serious adverse events (SAEs) during the 12-month period preceding each annual study visit [ Time Frame: 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
3. Insulin requirements during a one-week period preceding each annual study visit [ Time Frame: 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
4. Incidence of severe hypoglycemic events during the 12-month period preceding each annual study visit [ Time Frame: 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.
5. HbA1c levels at each annual study visit [ Time Frame: 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
6. Incidence of all-cause mortality [ Time Frame: By month 144 status post last islet transplant ]
7. Donor-specific alloantibodies [ Time Frame: 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.

Biospecimen Retention:   Samples With DNA

Participants are given the option to provide consent for:

1. the collection and storage of blood samples for future research studies
2. the collection and storage of blood samples for future genetic (i.e., DNA) testing.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Cohort from Clinical Islet Transplantation (CIT) parent studies (refer to inclusion criteria) who continue:

• to have islet graft function and
• are on prescribed immunosuppression medications to prevent rejection of their transplant.

Criteria

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.

Contacts and Locations

Locations

United States, California

University of California, San Francisco

San Francisco, California, United States, 94143

United States, Florida

University of Miami

Miami, Florida, United States, 33136

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

University of Illinois

Chicago, Illinois, United States, 60612

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02493

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Clinical Islet Transplantation Consortium

Investigators

• Principal Investigator: Bernhard Hering, MD; University of Minnesota
• Principal Investigator: Ali Naji, PhD; University of Pennsylvania
• Principal Investigator: Camillo Ricordi, MD; University of Miami
• Principal Investigator: Andrew Posselt, MD, PhD; University of California, San Francisco
• Principal Investigator: Nicole Turgeon, MD; Emory University
• Principal Investigator: Xunrong Luo, MD, PhD; Northwestern University

More Information

Additional Information:

National Institute of Allergy and Infectious Diseases 

Division of Allergy, Immunology, and Transplantation (DAIT) 

National Institute of Diabetes and Digestive and Kidney Diseases 

Clinical Islet Transplantation Consortium 

Publications:

Rickels MR, Liu C, Shlansky-Goldberg RD, Soleimanpour SA, Vivek K, Kamoun M, Min Z, Markmann E, Palangian M, Dalton-Bakes C, Fuller C, Chiou AJ, Barker CF, Luning Prak ET, Naji A. Improvement in beta-cell secretory capacity after human islet transplantation according to the CIT07 protocol. Diabetes. 2013 Aug;62(8):2890-7. doi: 10.2337/db12-1802. Epub 2013 Apr 29.

Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, Secchi A, Brendel MD, Berney T, Brennan DC, Cagliero E, Alejandro R, Ryan EA, DiMercurio B, Morel P, Polonsky KS, Reems JA, Bretzel RG, Bertuzzi F, Froud T, Kandaswamy R, Sutherland DE, Eisenbarth G, Segal M, Preiksaitis J, Korbutt GS, Barton FB, Viviano L, Seyfert-Margolis V, Bluestone J, Lakey JR. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006 Sep 28;355(13):1318-30. doi: 10.1056/NEJMoa061267.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01369082
• Other Study ID Numbers: DAIT CIT-08
• First Posted: June 8, 2011
• Last Update Posted: November 9, 2017
• Last Verified: November 2017

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

islet allograft function; c-peptide production; maintenance immunosuppressive medications

Additional relevant MeSH terms:

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Cyclosporine; Sirolimus; Mycophenolic Acid; Tacrolimus; Cyclosporins; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Calcineurin Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents