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

NCT00566813 | Completed Phase 1 Results DMC

• 1 other identifier: IND11807-2004-0532
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

Diabetes Mellitus, Type 1; Islets of Langerhans Transplantation; Exenatide; Soluble tumor necrosis factor receptor

Outcome Measures

Primary Outcomes (3)

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

  * 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

  15 months after the last transplant

• Number of Participants With Insulin Independence at End of Study Participation

  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.

  End of 15 Month Study Participation/Follow-up

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

  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.

  At end of 15 month study participation

Study Arms (2)

Group 1 (Islet Cell Transplant)

ACTIVE COMPARATOR

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.

Drug: Islet Cell Transplant

Group 2 (Islet Cell Transplant plus)

ACTIVE COMPARATOR

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.

Drug: Islet Cell Transplant plus

Interventions

Islet Cell Transplant DRUG

1-3 allogeneic islet transplants; two doses of basiliximab 20 mg iv.; sirolimus po trough levels 10-15 ng/ml X 3 months, then 7-10 ng/ml; tacrolimus po trough levels 3-6 ng/ml

Also known as: Allogeneic islets

Group 1 (Islet Cell Transplant)

Islet Cell Transplant plus DRUG

1-3 allogeneic Islets of Langerhans transplantations; two doses of basiliximab 20 mg iv.; sirolimus po daily to maintatin serum levels 12-15 ng/mL for 3 months, and 7-10 ng/mL thereafter; tacrolimus po twice daily to maintain serum levels 3-6 ng/mL; etanercept 50 mg IV before islet transplant, 25 mg subcutaneously post-transplant days 3, 7, 10; exenatide subcutaneously 5 mcg pre-transplant and twice daily for I week, then increased to 10-mcg twice daily for 6 months after the last islet transplant.

Also known as: Islet Cell Transplant + Etanercept + Exenatide

Group 2 (Islet Cell Transplant plus)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• Gangemi 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 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Islets of Langerhans Transplantation; Etanercept; Exenatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Endocrine Surgical Procedures; Surgical Procedures, Operative; Transplantation; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Jose Oberholzer, MD
• Organization: University of Illinois at Chicago

jober@uic.edu

312-996-6771

Study Officials

• Jose Oberholzer, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Division of Transplantation

Study Record Dates

• First Submitted: November 30, 2007
• First Posted: December 4, 2007
• Study Start: November 1, 2004
• Primary Completion: July 5, 2010
• Study Completion: July 15, 2020
• Last Updated: April 6, 2021
• Results First Posted: November 19, 2018

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)