PolyTreg Immunotherapy in Islet Transplantation
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|ClinicalTrials.gov Identifier: NCT03444064|
Recruitment Status : Recruiting
First Posted : February 23, 2018
Last Update Posted : April 17, 2019
Islet transplantation is a relatively new procedure used in people with difficult to control Type 1 diabetes. Patients who receive an islet transplant take medication that suppresses their immune system and prevent rejection of the islet tissue. In spite of the strengths of the current immunosuppression regimen, it has failed to enhance single-donor success rates, and the majority of patients require 2 or more islet transplants to achieve insulin independence. The need for life-long, high-dose immunosuppression is also associated with substantial side effects, and continues to limit application of islet transplantation earlier in the course of the disease.
The investigators have learned that Regulatory T cells (Tregs), a small subset of cluster of differentiation 4+ (CD4+) T cells, have emerged as the major contributor to self-tolerance through suppression of activation and effector function of other immune cells. Tregs function by preventing the initiation of unwanted immune activation and by suppressing ongoing immune response to limit bystander tissue destruction. It has been suggested that infusion of Tregs before extensive graft damage may improve long-term graft outcomes.
This study is an open label, controlled, dose finding pilot study. Up to 18 participants will be recruited including 12 participants receiving the investigational treatment and 6 participants being assigned to control group. All participants will undergo the routine Standard of Care islet transplant procedure, and will be maintained on lower dose tacrolimus and sirolimus immunosuppression.
The primary goal is to assess the safety and feasibility of intravenous infusion of ex vivo-selected and ex vivo-expanded autologous PolyTregs in islet transplant patients. The other goal is to assess the effect of Tregs on beta cell function in islet transplant patients.
The control group (6) will receive the current Edmonton islet transplant induction therapy (Alemtuzumab with Etanercept and Anakinra). The intervention group (up to 12) will receive islet transplant with same induction therapy as control group and PolyTregs (400-1600 million) six weeks post- transplant and will be followed for 1 year to assess safety and preliminary efficacy of Treg therapy. The Treg product will be administered via a peripheral intravenous (IV) line primed with saline per established standard operating procedures in approximately 20 to 30 minutes. The intravenous line will be maintained after the infusion and the participant will be asked to remain in the hospital for 24 hours. All participants will be maintained on low dose tacrolimus and sirolimus immunosuppression.
The investigators will also use retrospective data from the islet transplant cohort receiving Tac/mycophenolate mofetil(MMF) with alemtuzumab (>100 patients).
All study participants will be followed up for 58 weeks. Tests and assessments will be performed at each key study visit and will be allowed for +/- 2 weeks to accommodate scheduling.
The following measurements will be recorded at each key study visit :
Blood work, including the following:
Complete blood count (CBC) and differential
Creatinine and electrolytes
Fasting glucose and c-peptide
Any adverse events
Body weight (kg)
Vital signs (BP, HR)
Glucose records for self-monitoring.
Insulin use (total daily dose)
Autoantibodies and autoreactive T cell
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Diabetes Mellitus, Type 1||Biological: PolyTregs||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Polyclonal Regulatory T Cell (PolyTreg) Immunotherapy in Islet Transplantation|
|Actual Study Start Date :||February 1, 2018|
|Estimated Primary Completion Date :||March 2020|
|Estimated Study Completion Date :||March 2021|
No Intervention: Control
Participants in this arm receive islet transplant only, and no PolyTregs.
Participants in this arm receive PolyTregs infusion at week 6 post islet transplant.
Treatment group receive PolyTregs 6 weeks after islet transplantation as immunotherapy to improve islet survival and reduce the need for immunosuppression drugs.
Other Name: Ex vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T cells
- Adverse Events [ Time Frame: 58 weeks ]Any adverse event that occurs during the study
- Stimulated C-peptide level [ Time Frame: Baseline ]Stimulated C-peptide response during Mixed Meal Tolerance Test (MMTT)
- Stimulated C-peptide level [ Time Frame: Day 30 post islet transplant ]Stimulated C-peptide response during Mixed Meal Tolerance Test (MMTT)
- Stimulated C-peptide level [ Time Frame: Day 90 post islet transplant ]Stimulated C-peptide response during Mixed Meal Tolerance Test (MMTT)
- Stimulated C-peptide level [ Time Frame: Week 58 post islet transplant ]Stimulated C-peptide response during Mixed Meal Tolerance Test (MMTT)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03444064
|Contact: Andrew Malcolm, PhDfirstname.lastname@example.org|
|Contact: Parastoo Dinyari, BScemail@example.com|
|University of Alberta||Recruiting|
|Edmonton, Alberta, Canada, T6G 2C8|
|Contact: Andrew Malcolm, PhD (780) 407-6952 firstname.lastname@example.org|
|Contact: Parastoo Dinyari, BSc (780) 407-3904 email@example.com|
|Principal Investigator: James Shapiro, MD PhD|
|Principal Investigator:||James Shapiro, MD, PhD||University of Alberta|