Extended Follow-Up After Islet Transplantation in T1D

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
Clinical Islet Transplantation Consortium
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01369082
First received: June 3, 2011
Last updated: August 26, 2015
Last verified: August 2015
  Purpose

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 Intervention Phase
Type 1 Diabetes (T1D)
Islet Transplantation
Drug: Maintenance Immunosuppressive Treatment
Phase 3

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Extended Follow-Up After Islet Transplantation in Type 1 Diabetes (CIT-08)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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:
  • 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 ] [ Designated as safety issue: Yes ]
    Measured as part of each annual follow-up evaluation

  • 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 ] [ Designated as safety issue: Yes ]
    Insulin usage will be estimated from the one-week self report values

  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 36 months, 48 months, 60 months, 72 months, 84 months, 96 months, 108 months, 120 months, 132 months and 144 months ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    Glycosylated hemoglobin test determination during each follow-up visit

  • Incidence of all-cause mortality [ Time Frame: By month 144 status post last islet transplant ] [ Designated as safety issue: No ]
  • Donor-specific alloantibodies [ Time Frame: By month 144 status post last islet transplant ] [ Designated as safety issue: No ]
    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.

Estimated Enrollment: 75
Study Start Date: May 2011
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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®

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)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01369082

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
Clinical Islet Transplantation Consortium
Investigators
Principal Investigator: Bernhard Hering, MD University of Minnesota - Clinical and Translational Science Institute
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:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01369082     History of Changes
Other Study ID Numbers: DAIT CIT-08
Study First Received: June 3, 2011
Last Updated: August 26, 2015
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Data and Safety Monitoring Board
United States: Food and Drug Administration

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
Autoimmune Diseases
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Immunosuppressive Agents
Mycophenolate mofetil
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015