Islet Transplantation in Type 1 Diabetic Patients Using the University of Illinois at Chicago (UIC) Protocol

NCT00679042 | Active Not Recruiting Phase 3 Results DMC

• 1 other identifier: IND11807-2007-0330
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

In an earlier Phase 1/2 clinical trial using the Edmonton Protocol of steroid free immunosuppression, investigators at University of Illinois at Chicago (UIC) demonstrated the safety of islet preparation, iset transplantation, and medical treatment at UIC. Therefore, the primary purpose of the present Phase 3 clinical trial is to demonstrate the safety and efficacy of allogeneic islet transplantation in improving glycemic control in Type 1 diabetic patients using the UIC protocol that was developed and proven effective during the Phase 1/2 clinical trial.

Conditions

Type 1 Diabetes Mellitus

Keywords

Diabetes Mellitus Type 1; Type 1 Diabetes Mellitus; Islets of Langerhans Transplantation; Allogeneic Islet transplantation

Outcome Measures

Primary Outcomes (2)

• Treatment Emergent Adverse Events

  Safety endpoints: Incidence and severity of events related to islet infusion, immunosuppression, and islet preparations

  From first islet transplant through one year after last transplant (maximum 3 infusions possible), an average of 1 year

• Number of Subjects Reaching the Efficacy Goal

  A successful primary endpoint was defined as HbA1c ≤ 6.5% at the one-year follow-up visit and absence of severe hypoglycemic events (SHE) from Day 28 post-first transplant to 1 year after first and last transplant. The primary analysis was to estimate the true rate of the composite favorable outcome at 1 year following first and last transplant in patients in the ITT population.

  One year after islet transplant

Secondary Outcomes (3)

• Number of Patients Presenting With Insulin Independence at Day 365 Post First and Last Transplant

  1 year after islet infusion

• Hypoglycemic Episodes by HYPO Score

  One year after the last transplant

• Reduction in Hypoglycemic Severity Measured by %Reduction in HYPO Score

  One year after the first and last transplant

Study Arms (1)

Treatment

EXPERIMENTAL

All subjects will receive up to 3 transplantations of allogeneic human islets of Langerhans.

Biological: Islets of Langerhans transplantation

Interventions

Islets of Langerhans transplantation BIOLOGICAL

Each subject may receive 1-3 transplantations of allogeneic human islets of Langerhans and the following medications: Basiliximab 20 mg iv 2 hours before transplant and 20 mg iv 2 weeks post-transplant; Tacrolimus 1 mg p.o. bid adjusted to reach target trough levels of 3-6 ng/ml; Sirolimus 0.2 mg/kg loading dose, then 0.1 mg/kg p.o. daily adjusted to reach target trough levels of 10-15 ng/ml during the first 3 months post transplant and 7-10 ng/ml thereafter; Etanercept 50 mg iv 1 hour before transplant and 25 mg s.c. on days 3, 7,and 10 post-transplant; Exenatide 5-mcg s.c. bid for 1 week, then 10 mcg bid for 6 months after each transplant

Also known as: Islets of Langerhan (Islets), Basiliximab (Simulect®), Tacrolimus (Prograf®), Sirolimus (Rapamune®), Etanercept(Enbrel®), Exenatide (Byetta®)

Treatment

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 mellitus for more than 5 years complicated by the following situations that persist despite intensive insulin management efforts:
• At least one episode of severe hypoglycemia in the past 3 years 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
• Reduced awareness of hypoglycemia, defined by the absence of adequate autonomic symptoms at capillary glucose levels of \<54 mg/dL (3 mmol/l) as reported by the subject

You may not qualify if:

• Co-existing cardiac disease: myocardial infarction within the past 6 months, angiographic evidence of non-correctable coronary artery disease, ischemia on functional cardiac exam, heart failure
• Active alcohol or substance abuse, including cigarette smoking (must be abstinent for six months)
• Psychiatric disorder: schizophrenia, bipolar disorder, or major depression that is unstable on medication
• History of 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
• Family history of MEN2 or MCT
• Stroke within the past 6 months
• BMI \>27 kg/m2
• 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 75 years
• Creatinine clearance \<80 mL/min/1.73 m2 by 24-hour urine collection
• Serum creatinine consistently \>1.5 mg/dL

Sponsors & Collaborators

• CellTrans Inc.: lead

Study Sites (1)

University of Illinois at Chicago Medical Center

Chicago, Illinois, 60612, United States

Location

Related Publications (2)

• Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.

  PMID: 39735417 DERIVED

• Luu QF, Villareal CJ, Fritschi C, Monson RS, Oberholzer J, Danielson KK. Concerns and hopes of patients with type 1 diabetes prior to islet cell transplantation: A content analysis. J Diabetes Complications. 2018 Jul;32(7):677-681. doi: 10.1016/j.jdiacomp.2018.04.002. Epub 2018 Apr 17.

  PMID: 29779835 DERIVED

Related Links

• The Chicago Diabetes Project Homepage

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Islets of Langerhans Transplantation; Basiliximab; Tacrolimus; Sirolimus; 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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Constant Regions; 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: Jennifer Cook
• Organization: CellTrans Inc.

jenny@celltransinc.com

312-413-7727

Study Officials

• Jose Oberholzer, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adjunct Professor of Surgery
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 13, 2008
• First Posted: May 16, 2008
• Study Start: September 5, 2007
• Primary Completion: July 19, 2017
• Study Completion: June 14, 2026
• Last Updated: October 22, 2024
• Results First Posted: April 6, 2021

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)