Ignite Creation Date:
2024-05-06 @ 11:10 AM
Last Modification Date:
2024-10-26 @ 12:41 PM
Study NCT ID:
NCT03444064
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-09-14
First Post:
2018-02-16
Brief Title:
PolyTreg Immunotherapy in Islet Transplantation
Sponsor:
University of Alberta
Organization:
University of Alberta
Study Overview
Official Title:
Polyclonal Regulatory T Cell PolyTreg Immunotherapy in Islet Transplantation
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 Tacmycophenolate mofetilMMF 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
Physical examination
Body weight kg
Vital signs BP HR
Glucose records for self-monitoring
Hemoglobin A1c
Insulin use total daily dose
Autoantibodies and autoreactive T cell
MMTT
Immune profile
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 Tacmycophenolate mofetilMMF 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
Physical examination
Body weight kg
Vital signs BP HR
Glucose records for self-monitoring
Hemoglobin A1c
Insulin use total daily dose
Autoantibodies and autoreactive T cell
MMTT
Immune profile
Detailed Description:
BACKGROUND
Type 1 diabetes mellitus T1DM is an autoimmune disease characterized by the destruction of pancreatic beta β-cells resulting in absolute deficiency of insulin To date clinical islet transplantation is an accepted modality to treat select patients who exhibit frequent hypoglycemic events and severe glycemic liability The Edmonton Protocol became a milestone by reporting sustained C-peptide production and high rates of insulin-independence after transplant in patients with T1DM Due to the challenges associated with allo- and autoimmunity in islet transplantation appropriate immunosuppression is necessary to prevent acute andor long-term rejection Current immunosuppression protocols used in Edmonton and many other international sites for islet transplantation consist of a combination of induction anti-inflammatory and maintenance therapy accounting for higher success rates of islet transplantation In spite of the strengths of the current immunosuppression regimen described above it has failed to enhance single-donor success rates 15 with the majority of patients requiring 2 or more islet transplants to achieve insulin independence In Edmonton clinical trials are designed to improve islet isolation engraftment and long-term graft survival The need for life-long high-dose immunosuppression is associated with substantial side effects and continues to limit application of islet transplantation earlier in the course of the disease
Regulatory T cells Tregs are a small subset of CD4 T cells that depend on the FOXP3 transcription factor for their lineage differentiation and function Tregs 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 responses to limit bystander tissue destruction It has been suggested that infusion of Tregs before extensive graft damage may improve long-term graft outcomes Unlike generalized immunosuppressive regimens Tregs are long-lived and can function in a dominant and antigen-specific manner Thus therapeutic infusion of Tregs has the potential to induce long-term donor-specific tolerance without impeding desired immune responses to pathogens and tumors in transplant patients In terms of diabetes both animal and human studies demonstrate the central role of Tregs in preserving β-cell function Infusion of Tregs prevents and even reverses diabetes in non-obese diabetic NOD mice It has been demonstrated in animal studies that infused Tregs migrate to the allograft site shortly after transplantation and can induce stable islet graft survival without immunosuppression Recent human studies report functional defects of Tregs in T1DM which appear to be reversible
This clinical trial is collaboration between Dr Shapiros Clinical Islet Transplantation Program team in Edmonton Alberta with Drs Tang and Bluestones teams at the University of California San Francisco UCSF Drs Tang and Bluestone have been instrumental in developing PolyTreg technology providing an opportunity for this exciting collaboration in a clinical trial of Treg infusion in islet transplantation Dr Tangs team focuses on translating knowledge on mechanisms of immune tolerance into novel therapeutics for treating autoimmune diabetes and preventing transplant rejection They have demonstrated the efficacy of Tregs at multiple levels to halt tissue destruction in diabetic mouse models by subverting fully differentiated effector T-cells Dr Bluestones research over the past 25 years has focused on understanding the basic processes that control T-cell activation and immune tolerance in autoimmunity and organ transplantation including a special emphasis on Tregs Dr Bluestone has demonstrated that PolyTreg immunotherapy can be safely administered in adult patients with new onset T1DM Drs Tang and Bluestone have abundant experience in Treg isolation and production and Treg immunotherapy and bring strong technical and scientific support to this project The investigators expect that this collaboration will integrate the strengths of both Treg immunotherapy and the standard treatment for islet transplant Hence this trial is to investigate the safety and efficacy of Treg infusion incorporated into the current protocol for islet transplantation in the hope of finding more effective alternatives to the current immunosuppression regimen in islet transplantation
TRIAL DESIGN
Based on existing pre-clinical and clinical findings the investigators hypothesize that Tregs protect from both auto and allorejection of transplanted islets thereby improving insulin independent durability and C-peptide function over time in adults with T1DM
Primary Objective
To assess the safety and feasibility of intravenous infusion of ex vivo-selected and ex vivo-expanded autologous polyTregs in islet transplant patients
Primary Outcome MeasureEndpoint
Adverse events
Laboratory abnormalities
Signs of toxicity
Infusion reactions
Complications related to infection
Secondary Objective
To assess effects on endogenous insulin secretion Assess the effect of Tregs on b cell function in islet transplant patients
Secondary Outcome MeasureEndpoint
C-peptide response during MMTTs
Insulin use
HbA1C
Exploratory Objective
Surrogate markers of diabetes immune response Measure the effect of PolyTregs on the pathologic autoimmune and allo-immune responses
Exploratory Outcome MeasureEndpoint Multicolor flow cytometry MFC to assess effect on immune profile pre- infusion 1 2 4 weeks and 3 6 and 12 months post-infusion
Autoantibodies and autoreactive T cell using tetrameror ELISA spot assay pre-infusion and 3 6 and 12 months post infusion
Persistence and stability of infused PolyTregs in blood using deuterium labelling Days 1 7 14 28 3 months6 months and 12 months after infusion
This trial design will allow determination of the following specific aims
To demonstrate the safety of PolyTreg immunotherapy in islet transplantation in Type 1 diabetic patients
To assess the immunological impact of PolyTreg immunotherapy on patients receiving islet transplant
To assess the efficacy and to establish the optimal dose for PolyTreg immunotherapy
The investigators propose that PolyTregs will protectdampen both auto and allo-rejection thereby improving insulin independent durability and C-peptide function over time In this trial the investigators propose low level TacSirolimus immunosuppression the investigators hope that less early exposure and long-term exposure to high dose tacrolimus will lead to marked improvement in Beta cell function less renal dysfunction less opportunistic infections less Posttransplant lymphoproliferative disease PTLD The long-term goal is to develop and optimize PolyTreg dosing for a subsequent Phase 2 efficacysafety randomized controlled trial RCT
STUDY PROCEDURES
Study participants will undergo a screening evaluation for this study This will include the screening for standard of care islet transplant For women of child bearing potential the investigators will ask to confirm they are not pregnant with a blood test If the patient is eligible and has consented to take part he she will be assigned into either the control group or treatment group at the investigators discretion The only difference between the two groups will be that the treatment group will receive PolyTregs infusion and the control group will not receive PolyTregs infusion The investigators will collect certain details from his her medical records including age sex ethnicity and medical information If the patient is assigned into the treatment group a blood sample of 400 mL will be collected for PolyTregs manufacturing which will be infused back to the patient at week 6 after islet transplant The investigators will enrol two participants in the control group at first and will proceed with further enrolment for both groups if the procedure appears safe in the first two patients
For treatment group
Study visit 1 Pre-islet transplant
Before initiation of islet transplant induction therapy a total of 400 ml whole blood will be collected and immediately transported to the UCSF for PolyTregs manufacturing
Study visit 2 Islet transplant
At this visit participants will undergo islet transplant according to the current standard procedures at the University of Alberta Hospital The only difference will be the use of lower doses of TacrolimusSirolimus for immunosuppression
Study visit 3 30 days 7 days post-islet transplant
At visit 2 participants will have standard of care metabolic testing and blood samples taken in the Clinical Investigation Unit CIU at the University of Alberta Hospital UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review participants insulin usage blood glucose records In addition a blood sample will be collected for the testing of immune profiles antibodies and T cell function
Study visit 4 PolyTreg infusion 6 weeks 7 days post-islet transplant
The participant will be admitted to UAH at week 6 post-islet transplantation for PolyTregs infusion He she will stay at the UAH for 24 hours for monitoring after the infusion A blood sample will be collected to assess the persistence and stability of infused PolyTregs while the participant stays in the hospital
Study visit 5 1 week 2 days post-PolyTregs infusion
A blood sample will be collected at UAH at Day 7 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs and participants immune profiles
Study visit 6 2 weeks 4 days post-PolyTregs infusion
A blood sample will be collected at UAH at Day 14 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs and participants immune profiles
Study visit 7 4 weeks 7 days post-PolyTregs infusion
A blood sample will be collected at UAH at Day 28 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs and participants immune profiles
Study visit 8 6 weeks 7 days post-PolyTregs infusion 12 weeks 7 days post-islet transplant
At this visit participants will have standard of care metabolic testing and blood samples taken in the CIU at the UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review participants insulin usage blood glucose records
Study visit 9 12 weeks 7 days post-PolyTregs infusion
A blood sample will be collected at UAH at week 12 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs immune profiles and antibodies and T cell function
Study visit 10 26 weeks 30 days post-PolyTregs infusion
A blood sample will be collected at UAH at week 26 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs immune profiles and antibodies and T cell function
Study visit 11 52 weeks 30 days post-PolyTregs infusion
A blood sample will be collected at UAH at week 52 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs immune profiles and antibodies and T cell function Participants will also have standard of care metabolic testing and blood samples taken in the CIU at UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review participants insulin usage blood glucose records
Long-term Standard of Care Follow-up
After study visit 11 participants will be followed by the standard of care schedule for islet transplant
For control group
Study visit 1 Islet transplant
At this visit participants will undergo islet transplant according to the current standard procedures at the University of Alberta Hospital The only difference will be the use of lower doses of Tacrolimus Sirolimus for immunosuppression
Study visit 2 30 days 7 days post-islet transplant
At visit 2 participants will have standard of care metabolic testing and blood samples taken in the Clinical Investigation Unit CIU at the University of Alberta Hospital UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review patients insulin usage blood glucose records In addition a blood sample will be collected for the testing of immune profiles antibodies and T cell function
Study visit 3 7 weeks 7 days post-islet transplant
At visit 3 a blood sample will be collected at UAH to assess participants immune profiles
Study visit 4 8 weeks 7 days post-islet transplant
At visit 4 a blood sample will be collected at UAH to assess participants immune profiles
Study visit 5 10 weeks 7 days post-islet transplant
At visit 5 a blood sample will be collected at UAH to assess participants immune profiles
Study visit 6 12 weeks 7 days post-islet transplant
At this visit participants will have standard of care metabolic testing and blood samples taken in the Clinical Investigation Unit CIU at the University of Alberta Hospital UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review patients insulin usage blood glucose records
Study visit 7 18 weeks 7 days post-islet transplant
At visit 7 a blood sample will be collected at UAH to assess participants immune profiles and antibodies and T cell function
Study visit 8 32 weeks 30 days post-islet transplant
At visit 8 a blood sample will be collected at UAH to assess participants immune profiles and antibodies and T cell function
Study visit 9 58 weeks 30 days post-islet transplant
At visit 9 a blood sample will be collected at UAH to assess participants immune profiles and antibodies and T cell function Study participants will also have standard of care metabolic testing and blood samples taken in the CIU at UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review participants insulin usage blood glucose records
Long-term Standard of Care Follow-up
After study visit 9 participants will be followed by the standard of care schedule for islet transplant
Type 1 diabetes mellitus T1DM is an autoimmune disease characterized by the destruction of pancreatic beta β-cells resulting in absolute deficiency of insulin To date clinical islet transplantation is an accepted modality to treat select patients who exhibit frequent hypoglycemic events and severe glycemic liability The Edmonton Protocol became a milestone by reporting sustained C-peptide production and high rates of insulin-independence after transplant in patients with T1DM Due to the challenges associated with allo- and autoimmunity in islet transplantation appropriate immunosuppression is necessary to prevent acute andor long-term rejection Current immunosuppression protocols used in Edmonton and many other international sites for islet transplantation consist of a combination of induction anti-inflammatory and maintenance therapy accounting for higher success rates of islet transplantation In spite of the strengths of the current immunosuppression regimen described above it has failed to enhance single-donor success rates 15 with the majority of patients requiring 2 or more islet transplants to achieve insulin independence In Edmonton clinical trials are designed to improve islet isolation engraftment and long-term graft survival The need for life-long high-dose immunosuppression is associated with substantial side effects and continues to limit application of islet transplantation earlier in the course of the disease
Regulatory T cells Tregs are a small subset of CD4 T cells that depend on the FOXP3 transcription factor for their lineage differentiation and function Tregs 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 responses to limit bystander tissue destruction It has been suggested that infusion of Tregs before extensive graft damage may improve long-term graft outcomes Unlike generalized immunosuppressive regimens Tregs are long-lived and can function in a dominant and antigen-specific manner Thus therapeutic infusion of Tregs has the potential to induce long-term donor-specific tolerance without impeding desired immune responses to pathogens and tumors in transplant patients In terms of diabetes both animal and human studies demonstrate the central role of Tregs in preserving β-cell function Infusion of Tregs prevents and even reverses diabetes in non-obese diabetic NOD mice It has been demonstrated in animal studies that infused Tregs migrate to the allograft site shortly after transplantation and can induce stable islet graft survival without immunosuppression Recent human studies report functional defects of Tregs in T1DM which appear to be reversible
This clinical trial is collaboration between Dr Shapiros Clinical Islet Transplantation Program team in Edmonton Alberta with Drs Tang and Bluestones teams at the University of California San Francisco UCSF Drs Tang and Bluestone have been instrumental in developing PolyTreg technology providing an opportunity for this exciting collaboration in a clinical trial of Treg infusion in islet transplantation Dr Tangs team focuses on translating knowledge on mechanisms of immune tolerance into novel therapeutics for treating autoimmune diabetes and preventing transplant rejection They have demonstrated the efficacy of Tregs at multiple levels to halt tissue destruction in diabetic mouse models by subverting fully differentiated effector T-cells Dr Bluestones research over the past 25 years has focused on understanding the basic processes that control T-cell activation and immune tolerance in autoimmunity and organ transplantation including a special emphasis on Tregs Dr Bluestone has demonstrated that PolyTreg immunotherapy can be safely administered in adult patients with new onset T1DM Drs Tang and Bluestone have abundant experience in Treg isolation and production and Treg immunotherapy and bring strong technical and scientific support to this project The investigators expect that this collaboration will integrate the strengths of both Treg immunotherapy and the standard treatment for islet transplant Hence this trial is to investigate the safety and efficacy of Treg infusion incorporated into the current protocol for islet transplantation in the hope of finding more effective alternatives to the current immunosuppression regimen in islet transplantation
TRIAL DESIGN
Based on existing pre-clinical and clinical findings the investigators hypothesize that Tregs protect from both auto and allorejection of transplanted islets thereby improving insulin independent durability and C-peptide function over time in adults with T1DM
Primary Objective
To assess the safety and feasibility of intravenous infusion of ex vivo-selected and ex vivo-expanded autologous polyTregs in islet transplant patients
Primary Outcome MeasureEndpoint
Adverse events
Laboratory abnormalities
Signs of toxicity
Infusion reactions
Complications related to infection
Secondary Objective
To assess effects on endogenous insulin secretion Assess the effect of Tregs on b cell function in islet transplant patients
Secondary Outcome MeasureEndpoint
C-peptide response during MMTTs
Insulin use
HbA1C
Exploratory Objective
Surrogate markers of diabetes immune response Measure the effect of PolyTregs on the pathologic autoimmune and allo-immune responses
Exploratory Outcome MeasureEndpoint Multicolor flow cytometry MFC to assess effect on immune profile pre- infusion 1 2 4 weeks and 3 6 and 12 months post-infusion
Autoantibodies and autoreactive T cell using tetrameror ELISA spot assay pre-infusion and 3 6 and 12 months post infusion
Persistence and stability of infused PolyTregs in blood using deuterium labelling Days 1 7 14 28 3 months6 months and 12 months after infusion
This trial design will allow determination of the following specific aims
To demonstrate the safety of PolyTreg immunotherapy in islet transplantation in Type 1 diabetic patients
To assess the immunological impact of PolyTreg immunotherapy on patients receiving islet transplant
To assess the efficacy and to establish the optimal dose for PolyTreg immunotherapy
The investigators propose that PolyTregs will protectdampen both auto and allo-rejection thereby improving insulin independent durability and C-peptide function over time In this trial the investigators propose low level TacSirolimus immunosuppression the investigators hope that less early exposure and long-term exposure to high dose tacrolimus will lead to marked improvement in Beta cell function less renal dysfunction less opportunistic infections less Posttransplant lymphoproliferative disease PTLD The long-term goal is to develop and optimize PolyTreg dosing for a subsequent Phase 2 efficacysafety randomized controlled trial RCT
STUDY PROCEDURES
Study participants will undergo a screening evaluation for this study This will include the screening for standard of care islet transplant For women of child bearing potential the investigators will ask to confirm they are not pregnant with a blood test If the patient is eligible and has consented to take part he she will be assigned into either the control group or treatment group at the investigators discretion The only difference between the two groups will be that the treatment group will receive PolyTregs infusion and the control group will not receive PolyTregs infusion The investigators will collect certain details from his her medical records including age sex ethnicity and medical information If the patient is assigned into the treatment group a blood sample of 400 mL will be collected for PolyTregs manufacturing which will be infused back to the patient at week 6 after islet transplant The investigators will enrol two participants in the control group at first and will proceed with further enrolment for both groups if the procedure appears safe in the first two patients
For treatment group
Study visit 1 Pre-islet transplant
Before initiation of islet transplant induction therapy a total of 400 ml whole blood will be collected and immediately transported to the UCSF for PolyTregs manufacturing
Study visit 2 Islet transplant
At this visit participants will undergo islet transplant according to the current standard procedures at the University of Alberta Hospital The only difference will be the use of lower doses of TacrolimusSirolimus for immunosuppression
Study visit 3 30 days 7 days post-islet transplant
At visit 2 participants will have standard of care metabolic testing and blood samples taken in the Clinical Investigation Unit CIU at the University of Alberta Hospital UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review participants insulin usage blood glucose records In addition a blood sample will be collected for the testing of immune profiles antibodies and T cell function
Study visit 4 PolyTreg infusion 6 weeks 7 days post-islet transplant
The participant will be admitted to UAH at week 6 post-islet transplantation for PolyTregs infusion He she will stay at the UAH for 24 hours for monitoring after the infusion A blood sample will be collected to assess the persistence and stability of infused PolyTregs while the participant stays in the hospital
Study visit 5 1 week 2 days post-PolyTregs infusion
A blood sample will be collected at UAH at Day 7 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs and participants immune profiles
Study visit 6 2 weeks 4 days post-PolyTregs infusion
A blood sample will be collected at UAH at Day 14 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs and participants immune profiles
Study visit 7 4 weeks 7 days post-PolyTregs infusion
A blood sample will be collected at UAH at Day 28 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs and participants immune profiles
Study visit 8 6 weeks 7 days post-PolyTregs infusion 12 weeks 7 days post-islet transplant
At this visit participants will have standard of care metabolic testing and blood samples taken in the CIU at the UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review participants insulin usage blood glucose records
Study visit 9 12 weeks 7 days post-PolyTregs infusion
A blood sample will be collected at UAH at week 12 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs immune profiles and antibodies and T cell function
Study visit 10 26 weeks 30 days post-PolyTregs infusion
A blood sample will be collected at UAH at week 26 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs immune profiles and antibodies and T cell function
Study visit 11 52 weeks 30 days post-PolyTregs infusion
A blood sample will be collected at UAH at week 52 after PolyTregs infusion to assess the persistence and stability of infused PolyTregs immune profiles and antibodies and T cell function Participants will also have standard of care metabolic testing and blood samples taken in the CIU at UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review participants insulin usage blood glucose records
Long-term Standard of Care Follow-up
After study visit 11 participants will be followed by the standard of care schedule for islet transplant
For control group
Study visit 1 Islet transplant
At this visit participants will undergo islet transplant according to the current standard procedures at the University of Alberta Hospital The only difference will be the use of lower doses of Tacrolimus Sirolimus for immunosuppression
Study visit 2 30 days 7 days post-islet transplant
At visit 2 participants will have standard of care metabolic testing and blood samples taken in the Clinical Investigation Unit CIU at the University of Alberta Hospital UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review patients insulin usage blood glucose records In addition a blood sample will be collected for the testing of immune profiles antibodies and T cell function
Study visit 3 7 weeks 7 days post-islet transplant
At visit 3 a blood sample will be collected at UAH to assess participants immune profiles
Study visit 4 8 weeks 7 days post-islet transplant
At visit 4 a blood sample will be collected at UAH to assess participants immune profiles
Study visit 5 10 weeks 7 days post-islet transplant
At visit 5 a blood sample will be collected at UAH to assess participants immune profiles
Study visit 6 12 weeks 7 days post-islet transplant
At this visit participants will have standard of care metabolic testing and blood samples taken in the Clinical Investigation Unit CIU at the University of Alberta Hospital UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review patients insulin usage blood glucose records
Study visit 7 18 weeks 7 days post-islet transplant
At visit 7 a blood sample will be collected at UAH to assess participants immune profiles and antibodies and T cell function
Study visit 8 32 weeks 30 days post-islet transplant
At visit 8 a blood sample will be collected at UAH to assess participants immune profiles and antibodies and T cell function
Study visit 9 58 weeks 30 days post-islet transplant
At visit 9 a blood sample will be collected at UAH to assess participants immune profiles and antibodies and T cell function Study participants will also have standard of care metabolic testing and blood samples taken in the CIU at UAH These tests assess the function of transplanted islets and include an arginine-stimulated c-peptide test and an Ensure test Blood samples will be taken at various time intervals over approximately 90 minutes and will test for HbA1c c-peptide insulin and glucose The investigators may also ask to review participants insulin usage blood glucose records
Long-term Standard of Care Follow-up
After study visit 9 participants will be followed by the standard of care schedule for islet transplant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None