Trial Outcomes & Findings for Study of Islet Transplantation in Type 1 Diabetic Kidney Transplant Recipients (NCT NCT00888628)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

7 participants

Primary outcome timeframe

1 year after the subject's first islet transplant

Results posted on

2017-11-29

Participant Flow

Participant milestones

Participant milestones
Measure	Islet Transplant Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
Overall Study STARTED	7
Overall Study Enrolled	7
Overall Study Screen Failure	2
Overall Study Withdrawn	1
Overall Study Transplanted	4
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Islet Transplantation in Type 1 Diabetic Kidney Transplant Recipients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Islet Transplant n=7 Participants Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year after the subject's first islet transplant

Outcome measures

Outcome measures
Measure	Islet Transplant n=4 Participants Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
Insulin Independence With Both an HbA1c ≤ 6.5% and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant or a Reduction in HbA1c of at Least 1 Point and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant.	4 participants

SECONDARY outcome

Timeframe: 1 year after subject's first islet transplant

Subjects will have a decrease in HbA1c of at least \>1%

Outcome measures

Outcome measures
Measure	Islet Transplant n=4 Participants Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
Number of Participants With a Decrease in HbA1c	4 Participants

SECONDARY outcome

Timeframe: 1 year after subjects initial islet transplant

Proteinuria and serum creatinine will be stable or decreased as compared to pre-transplant values

Outcome measures

Outcome measures
Measure	Islet Transplant n=4 Participants Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
Stable or Decrease in Urinary Albumin and Creatinine Ratio and Serum Creatinine	4 Participants

SECONDARY outcome

Timeframe: 1 year after the subject's first islet transplant

Outcome measures

Outcome measures
Measure	Islet Transplant n=4 Participants Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
An Absence Cardiovascular Events, Cerebral Vascular Accident, and Myocardial Infarction	4 Participants

SECONDARY outcome

Timeframe: 1 year after the subject's first islet transplant

Improvement of frequency of interventions and from changes in reported visual acuity with optical refraction and severity of diabetic retinopathy

Outcome measures

Outcome measures
Measure	Islet Transplant n=4 Participants Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
Impact on Vision	2 Participants

SECONDARY outcome

Timeframe: 1 year after the subject's first islet transplant

Loss of allograft survivial (return to dialysis, retransplant, death) and Renal allograft function meausred by SCr

Outcome measures

Outcome measures
Measure	Islet Transplant n=4 Participants Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
Absence of Negative Renal Impact Measures	4 Participants

SECONDARY outcome

Timeframe: 1 year after the subject's first islet transplant

Whether there is an improvement in metabolic control in IAK will be evaluated based on improvement in 1. basal c-peptide levels, 2. MMTT, 3. insulin requirements, and 4. c-peptide to glucose, creatinine ratio (CPGCR).

Outcome measures

Outcome measures
Measure	Islet Transplant n=4 Participants Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
Improvement of Metabolic Control	4 Participants

SECONDARY outcome

Timeframe: 1 year after subject's first transplant

Subjects will have a decrease in severe hypoglycemic events

Outcome measures

Outcome measures
Measure	Islet Transplant n=4 Participants Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
Number of Participants With a Decrease of Severe Hypoglycemic Events	4 Participants

SECONDARY outcome

Timeframe: 1 year after the subject's first islet transplant

Evidence of partial success will be considered for subjects who have a reduction in insulin requirements but who are not insulin independent. This will be assessed by comparing the pre-transplant insulin requirement expressed as insulin units per kg per day with the requirement preceding subsequent islet transplants and the insulin requirements at 6 months and 1, 2, and 3 years after the first and last transplant.

Outcome measures

Outcome measures
Measure	Islet Transplant n=4 Participants Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
Reduction of Insulin Requriements	4 Participants

Adverse Events

Islet Transplant

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Islet Transplant n=4 participants at risk Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
General disorders Allergic Reaction (Elevated Temp 104.7)	25.0% 1/4 • Number of events 1
Infections and infestations Soft tissue infection	25.0% 1/4 • Number of events 1
Investigations Hyperkalemia	25.0% 1/4 • Number of events 1
Gastrointestinal disorders Nausea and Vomiting	25.0% 1/4 • Number of events 1

Other adverse events

Other adverse events
Measure	Islet Transplant n=4 participants at risk Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes. Etanercept: Given as induction for islet cell transplant
Metabolism and nutrition disorders Hypoglycemia	75.0% 3/4 • Number of events 11
Cardiac disorders Hypertenstion	25.0% 1/4 • Number of events 3
Renal and urinary disorders Elevated Creatinine	50.0% 2/4 • Number of events 4
Infections and infestations Upper Respiratory Infection	25.0% 1/4 • Number of events 5
Gastrointestinal disorders Diarrhea	50.0% 2/4 • Number of events 4
Infections and infestations Urinary Tract Infection	25.0% 1/4 • Number of events 7

Additional Information

James F. Markmann, M.D. Ph.D - Chief, Division of Transplant Surgery

Massachusetts General Hospital

Phone: 617-643-4087

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place