Extended Follow-Up After Islet Transplantation in T1D

Islet Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01369082
• Other study ID #: DAIT CIT-08
• Status: Completed
• Phase: N/A
• First received: June 3, 2011
• Last updated: November 7, 2017
• Start date: May 2011
• Est. completion date: July 2017

Study information

• Verified date: November 2017
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Islet Transplantation
• Type 1 Diabetes (T1D)

Intervention

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.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	University of Miami	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of California, San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Clinical Islet Transplantation Consortium, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 ß-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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence of all-cause mortality		By month 144 status post last islet transplant
Secondary	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

External Links

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