Trial · Interventional

CompletedPhase 1/2Results postedRegistry data

Islet Transplantation in Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression

NCTNCT00566813Other idIND11807-2004-0532

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Overview

Status: Completed
Phase: Phase 1/2
Enrollment: 10 participants (actual)
Sponsor: University of Illinois at Chicago · Other
Design: Not randomized · Open label (no masking)
Countries: 1 country
United States
Start: Nov 2004
Primary completion: 5 Jul 2010
Completion: 15 Jul 2020
First posted: 4 Dec 2007 (estimated)
Last update posted: 6 Apr 2021
Conditions: Diabetes Mellitus, Type 1

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2005201020152020

Ph 1/2
Islet Transplantation in Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression
NCT00566813
Nov 2004 to 15 Jul 2020

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The primary purpose of this study is to demonstrate the safety of allogeneic islet transplantation in type 1 diabetic patients performed at the University of Illinois at Chicago (UIC). The purpose is to reproduce the Edmonton protocol to demonstrate that pancreatic islets isolated at UIC are safe and of sufficient quality to provide reproducible graft function.

Interventions

Islet Cell TransplantDrug
Islet Cell Transplant plusDrug

Arms2

Active comparator
Group 1 (Islet Cell Transplant)
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.
Active comparator
Group 2 (Islet Cell Transplant plus)
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.

Primary outcomes3

Outcomes the sponsor listed as primary.

Number of Participants With Adverse Events Including Laboratory Abnormalities at the End of Study Participation
Time frame · 15 months after the last transplant
Registry description
* 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
Number of Participants With Insulin Independence at End of Study Participation
Time frame · End of 15 Month Study Participation/Follow-up
Registry description
Primary 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.
Number of Participants With HbA1c Less Than or Equal to 6.5 & Free of Severe Hypoglycemic Events
Time frame · At end of 15 month study participation
Registry description
HbA1c 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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· 15 months after the last transplant

Number of Participants With Adverse Events Including Laboratory Abnormalities at the End of Study Participation

Group	Value (participants)
Islet Cells	4
Islet Cells + Etanercept + Exenatide	5

Primary outcomeNumber· End of 15 Month Study Participation/Follow-up

Number of Participants With Insulin Independence at End of Study Participation

Group	Value (participants)
Islet Cells	4
Islet Cells + Etanercept + Exenatide	5

Primary outcomeNumber· At end of 15 month study participation

Number of Participants With HbA1c Less Than or Equal to 6.5 & Free of Severe Hypoglycemic Events

Group	Value (participants)
Islet Cells	4
Islet Cells + Etanercept + Exenatide	5

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Islet Cells1-3 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.	–	0 / 4	4 / 4
Islet Cells + Etanercept + Exenatide1-3 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.	–	2 / 6	6 / 6

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

ResultGangemi A, Salehi P, Hatipoglu B, Martellotto J, Barbaro B, Kuechle JB, Qi M, Wang Y, Pallan P, Owens C, Bui J, West D, Kaplan B, Benedetti E, Oberholzer J. Islet transplantation for brittle type 1 diabetes: the UIC protocol. Am J Transplant. 2008 Jun;8(6):1250-61. doi: 10.1111/j.1600-6143.2008.02234.x. Epub 2008 Apr 29. PMID 18444920

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years up to 75 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: * Type 1 diabetes \> 5 years complicated by at least one of the following situations despite intensive insulin management: * Reduced awareness of hypoglycemia at plasma glucose levels \< 54 mg/dL * Metabolic lability/instability characterized by two or more episodes of severe hypoglycemia or hospital visits for diabetic ketoacidosis over the last year * Progressive secondary complications of diabetes: * Retinopathy-three step progression using the ETDRS grading system or equivalent progression; * Nephropathy- microalbuminuria rise of 50 µg/min (72 mg/24h) over three months within the past two years despite using an ACE inhibitor; * Neuropathy-persistent gastroparesis, postural hypotension, neuropathic bowel or bladder, or severe peripheral neuropathy unresponsive to management Exclusion Criteria: * Co-existing cardiac disease: * Myocardial infarction within past six months * Angiographic evidence of non-correctable coronary artery disease * Ischemia on functional cardiac exam d. Heart failure \> NYHA II * Active alcohol or substance abuse or cigarette smoking * Psychiatric disorder: schizophrenia, bipolar disorder, or major depression that is unstable on medication * Non-adherence to prescribed regimens * Active infection including hepatitis C, hepatitis B, HIV * TB by history, current infection, or under treatment for suspected TB * History of malignancies except squamous or basal skin cancer * Stroke within the past 6 months * BMI \> 26 kg/m2 or body weight \> 70 kg at screening visit * C-peptide response to glucagon stimulation, any C-peptide ≥ 0.3 ng/mL * Inability to provide informed consent * Age less than 18 or greater than 65 years * Creatinine clearance \< 85 mL/min/1.73 m2 by 24-hour urine collection * Serum creatinine \> 1.5 mg/dL * Macroalbuminuria \> 300 mg/24h * Baseline Hb \< 12 gm/dL in women, \< 13 gm/dL in men * Baseline liver function tests outside normal range * Untreated proliferative retinopathy * Positive pregnancy test, intent for pregnancy, male's intent to procreate, unwilling to use effective contraception, breast-feeding * Previous transplant or PRA reactivity \> 20%) * Insulin requirement \> 0.7 IU/kg/day * HbA1C \> 12% * Hyperlipidemia * Chronic use of steroids * Use of coumadin or other anticoagulant (except aspirin) or PT INR \> 1.5 * Addison's disease * Allergy to radiographic contrast material

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