Trial Outcomes & Findings for Islet Transplantation in Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression (NCT NCT00566813)
NCT ID: NCT00566813
Last Updated: 2021-04-06
Results Overview
* Frequency of adverse events including laboratory abnormalities * HbA1C (less than 6.1% is considered normal) * Glucose control and absence of hypoglycemic coma/unawareness, as evidenced by no further requirement for third-party assistance or hospital attendance resulting from a severe hypoglycemic episode * Renal function, measured both by serum creatinine and calculated GFR using the Cockroft \& Gault * Lipid profiles for cholesterol, triglycerides, low density lipoprotein (LDL) and high density lipoprotein (HDL) * PRA * Doppler ultrasound to exclude or document portal vein thrombosis * Immunosuppressive drug trough levels * Renal clearance (GFR) * Liver function tests * Diagnosis of opportunistic infections, e.g., CMV
COMPLETED
PHASE1/PHASE2
10 participants
15 months after the last transplant
2021-04-06
Participant Flow
Recruitment of adults ages 18-65 occurred from 10/22/2004 to 2/21/2006 when the 10th eligible participant was confirmed. Potential participants were recruited from physician referrals at University of Illinois (UIC) or private practice, from information posted on the UIC Transplant Division website, and from diabetes chat groups.
88 individuals completed phone screenings; 15 withdrew, 58 excluded mainly for high weight, kidney disease, high insulin use, lack of hypoglycemia unawareness, previous transplant. 36 enrolled to be screened for eligibility. Of the 36, 5 withdrew, 21 were excluded for not meeting eligibility requirements. Remaining 10 subjects received transplants.
Participant milestones
| Measure |
Group 1 (Islet Cells)
1-3 Islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for three months post-transplant and 7-10 ng/mL therafter; tacrolimus dosed to maintain serum trough levels 3-6 ng/mL throughout the study.
|
Group 2 (Islet Cells + Etanercept + Exenatide)
1-3 islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for 3 months post-transplant and 7-10 mg/mL thereafter; tacrolimus dosed to serum trough levels 3-6 ng/mL throughout the study; etanercept 50 mg IV pre-transplant, 25 mg subcutaneously post-transplant Days 3, 7, 10; exenatide 5-mcg subcutaneously twice daily for I week, then up to 10-mcg twice daily for 6 months after the last islet transplant.
|
|---|---|---|
|
Overall Study
STARTED
|
4
|
6
|
|
Overall Study
COMPLETED
|
4
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Islet Transplantation in Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression
Baseline characteristics by cohort
| Measure |
Islet Cells
n=4 Participants
Islet transplantation and the Edmonton protocol of steroid free immunosuppression
|
Islet Cells + Etanercept + Exenatide
n=6 Participants
Edmonton Protocol, etanercept ,exenatide
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
48.8 years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
44.5 years
STANDARD_DEVIATION 9.7 • n=7 Participants
|
46.2 years
STANDARD_DEVIATION 9.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
6 participants
n=7 Participants
|
10 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 15 months after the last transplantPopulation: The number of participants analyzed represents the number of subjects in Group 1 (Islet Cells) and Group 2 (Islet Cells + Etanercept + Exenatide)
* Frequency of adverse events including laboratory abnormalities * HbA1C (less than 6.1% is considered normal) * Glucose control and absence of hypoglycemic coma/unawareness, as evidenced by no further requirement for third-party assistance or hospital attendance resulting from a severe hypoglycemic episode * Renal function, measured both by serum creatinine and calculated GFR using the Cockroft \& Gault * Lipid profiles for cholesterol, triglycerides, low density lipoprotein (LDL) and high density lipoprotein (HDL) * PRA * Doppler ultrasound to exclude or document portal vein thrombosis * Immunosuppressive drug trough levels * Renal clearance (GFR) * Liver function tests * Diagnosis of opportunistic infections, e.g., CMV
Outcome measures
| Measure |
Islet Cells
n=4 Participants
1-3 Islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for three months post-transplant and 7-10 ng/mL therafter; tacrolimus dosed to maintain serum trough levels 3-6 ng/mL throughout the study.
|
Islet Cells + Etanercept + Exenatide
n=6 Participants
1-3 islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for 3 months post-transplant and 7-10 mg/mL thereafter; tacrolimus dosed to serum trough levels 3-6 ng/mL throughout the study; etanercept 50 mg IV pre-transplant, 25 mg subcutaneously post-transplant Days 3, 7, 10; exenatide 5-mcg subcutaneously twice daily for I week, then up to 10-mcg twice daily for 6 months after the last islet transplant.
|
|---|---|---|
|
Number of Participants With Adverse Events Including Laboratory Abnormalities at the End of Study Participation
|
4 participants
|
5 participants
|
PRIMARY outcome
Timeframe: End of 15 Month Study Participation/Follow-upPrimary efficacy outcome: independence from insulin injections with adequate control of blood glucose in subjects with Type 1 diabetes. Transplant is considered a success when 2 weeks after their last transplant, subjects are not using insulin, and fasting glucose levels do not exceed 7.8 mmol/L (140 mg/dL) more than 3 times/week, and two-hour post-prandial glucose values do not exceed 10 mmol/L (180 mg/dL) more than 4 times/week. During the 15 months after last transplant, a subject will be considered a success if an illness or other event (e.g., high tacrolimus level) causes need for insulin not exceeding 14 days providing evidence of graft rejection is not apparent. The proportion of subjects who are insulin independent and meet criteria for glucose control will be determined at 2 weeks and 1, 3, 6, 12, and 15 months following their final islet transplant.
Outcome measures
| Measure |
Islet Cells
n=4 Participants
1-3 Islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for three months post-transplant and 7-10 ng/mL therafter; tacrolimus dosed to maintain serum trough levels 3-6 ng/mL throughout the study.
|
Islet Cells + Etanercept + Exenatide
n=6 Participants
1-3 islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for 3 months post-transplant and 7-10 mg/mL thereafter; tacrolimus dosed to serum trough levels 3-6 ng/mL throughout the study; etanercept 50 mg IV pre-transplant, 25 mg subcutaneously post-transplant Days 3, 7, 10; exenatide 5-mcg subcutaneously twice daily for I week, then up to 10-mcg twice daily for 6 months after the last islet transplant.
|
|---|---|---|
|
Number of Participants With Insulin Independence at End of Study Participation
|
4 participants
|
5 participants
|
PRIMARY outcome
Timeframe: At end of 15 month study participationHbA1c less than or equal to 6.5 at end of 15 month study participation, and lack of or free from severe hypoglycemic events, defined as an event with symptoms compatible with hypoglycemia in which the subject required the assistance of another person and which was associated with either a blood glucose level \< 50 mg/dl (2.8 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration.
Outcome measures
| Measure |
Islet Cells
n=4 Participants
1-3 Islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for three months post-transplant and 7-10 ng/mL therafter; tacrolimus dosed to maintain serum trough levels 3-6 ng/mL throughout the study.
|
Islet Cells + Etanercept + Exenatide
n=6 Participants
1-3 islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for 3 months post-transplant and 7-10 mg/mL thereafter; tacrolimus dosed to serum trough levels 3-6 ng/mL throughout the study; etanercept 50 mg IV pre-transplant, 25 mg subcutaneously post-transplant Days 3, 7, 10; exenatide 5-mcg subcutaneously twice daily for I week, then up to 10-mcg twice daily for 6 months after the last islet transplant.
|
|---|---|---|
|
Number of Participants With HbA1c Less Than or Equal to 6.5 & Free of Severe Hypoglycemic Events
|
4 participants
|
5 participants
|
Adverse Events
Islet Cells
Islet Cells + Etanercept + Exenatide
Serious adverse events
| Measure |
Islet Cells
n=4 participants at risk
1-3 Islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for three months post-transplant and 7-10 ng/mL therafter; tacrolimus dosed to maintain serum trough levels 3-6 ng/mL throughout the study.
|
Islet Cells + Etanercept + Exenatide
n=6 participants at risk
1-3 islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for 3 months post-transplant and 7-10 mg/mL thereafter; tacrolimus dosed to serum trough levels 3-6 ng/mL throughout the study; etanercept 50 mg IV pre-transplant, 25 mg subcutaneously post-transplant Days 3, 7, 10; exenatide 5-mcg subcutaneously twice daily for I week, then up to 10-mcg twice daily for 6 months after the last islet transplant.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Intrahepatic hematoma
|
0.00%
0/4 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
16.7%
1/6 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
|
Injury, poisoning and procedural complications
Intraperitoneal hematoma
|
0.00%
0/4 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
16.7%
1/6 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
Other adverse events
| Measure |
Islet Cells
n=4 participants at risk
1-3 Islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for three months post-transplant and 7-10 ng/mL therafter; tacrolimus dosed to maintain serum trough levels 3-6 ng/mL throughout the study.
|
Islet Cells + Etanercept + Exenatide
n=6 participants at risk
1-3 islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for 3 months post-transplant and 7-10 mg/mL thereafter; tacrolimus dosed to serum trough levels 3-6 ng/mL throughout the study; etanercept 50 mg IV pre-transplant, 25 mg subcutaneously post-transplant Days 3, 7, 10; exenatide 5-mcg subcutaneously twice daily for I week, then up to 10-mcg twice daily for 6 months after the last islet transplant.
|
|---|---|---|
|
Blood and lymphatic system disorders
Transient anemia
|
100.0%
4/4 • Number of events 4 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
100.0%
6/6 • Number of events 6 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
|
Renal and urinary disorders
Increased creatinine
|
25.0%
1/4 • Number of events 1 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
33.3%
2/6 • Number of events 2 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
|
Gastrointestinal disorders
Temporary nausea, vomiting, and weight loss
|
0.00%
0/4 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
100.0%
6/6 • Number of events 6 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
|
Infections and infestations
Scalene muscle myonecrosis and vertebral osteomyelitis
|
0.00%
0/4 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
|
Reproductive system and breast disorders
Irregular menstrual bleeding and ruptured ovarian cyst
|
25.0%
1/4 • Number of events 1 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
0.00%
0/6 • Adverse event data were collected for 1 year following the last transplant.
Review of Systems and adverse events at each study visit, physical examinations, notification from subjects.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place