Extended Follow-Up After Islet Transplantation in T1D

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes (T1D); Islet Transplantation
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 75

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • University of Illinois
  • Massachusetts
    • Boston, Massachusetts, United States, 02493
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

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: FK506; tacrolimus; rapamycin; sirolimus; mycophenolate mofetil (MMF); Neoral®; CellCept®; Prograf®; Myfortic®; Rapamune®; cyclosporine; mycophenolic sodium

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: 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: Andrew Posselt, MD, PhD, University of California, San Francisco; Principal Investigator: Nicole Turgeon, MD, Emory University; Principal Investigator: Xunrong Luo, MD, PhD, Northwestern University

Publications and helpful links

General 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.

Helpful Links

• Division of Allergy, Immunology, and Transplantation (DAIT)
• National Institute of Allergy and Infectious Diseases
• National Institute of Diabetes and Digestive and Kidney Diseases
• Clinical Islet Transplantation Consortium

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: June 3, 2011
• First Submitted That Met QC Criteria: June 7, 2011
• First Posted (Estimate): June 8, 2011

Study Record Updates

• Last Update Posted (Actual): November 9, 2017
• Last Update Submitted That Met QC Criteria: November 7, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: islet allograft function; c-peptide production; maintenance immunosuppressive medications
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid; Sirolimus; Cyclosporine; Cyclosporins; Immunosuppressive Agents
• Other Study ID Numbers: DAIT CIT-08