Islet Transplantation in Patients With "Brittle" Type I Diabetes

The purpose of this study is to learn about the safety of islet transplantation for Type 1 diabetes mellitus, which may provide more normal control of blood sugar without the need for insulin shots. Islets are special clusters of cells within the pancreas that produce insulin. These cells will be obtained from cadaver (non-living) donors and given to subjects by vein.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Procedure: Intraportal infusion of islet cells; Biological: Allogenic islet cells (human, U. Chicago)

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lindsay Basto, RN, BSN; Phone Number: 773-702-2504; Email: Lindsay.Basto@uchospitals.edu
• Study Contact Backup: Name: Piotr Witkowski, MD, PhD; Phone Number: (773) 702-2447; Email: pwitkowski@surgery.bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
      • Principal Investigator: Piotr Witkowski, MD, PhD
      • Contact: Lindsay Basto, RN, BSN; Phone Number: 773-702-2504; Email: Lindsay.Basto@uchospitals.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients 18 to 70 years of age.
• Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol.
• Clinical history compatible with T1D with onset of disease at < 40 years of age, insulin-dependence for ≥ 5 years at the time of enrollment, and a sum of patient age and insulin dependent diabetes duration of ≥ 28 and absent stimulated c-peptide (<0.3ng/mL) in response to a mixed meal tolerance test (MMTT; Boost® 6 mL/kg body weight to a maximum of 360 mL; another product with equivalent caloric and nutrient content may be substituted for Boost) measured at 60 and 90 min after the start of consumption and at least one episode of severe hypoglycemia in the 12 months prior to study enrollment; OR a clinical history of "problematic hypoglycemia" defined as defined as two or more episodes per year of severe hypoglycemia or as one episode associated with impaired awareness of hypoglycemia, extreme glycemic lability, or major fear and maladaptive behavior according to recent clinical recommendations.
• Involvement in intensive diabetes management defined as self monitoring of glucose values no less than a mean of three times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. Such management must be under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least 3 clinical evaluations during the 12 months prior to study enrollment.
• Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more OR a HYPO score greater than or equal to the 90th percentile (1047) during the screening period and within the last 6 months; OR marked glycemic lability characterized by wide swings in blood glucose despite optimal diabetes therapy and defined by an LI score greater than or equal to the 90th percentile (433 mmol/L2/h -wk1) during the screening period and within the last 6 months prior to randomization; OR a composite of a Clarke score of 4 or more and a HYPO score greater than or equal to the 75th percentile (423) and a LI greater than or equal to the 75th percentile (329) during the screening period and within the last 6 months.

Exclusion Criteria:

• Body mass index (BMI) >30 kg/m2 or patient weight <50kg.
• Insulin requirement >1.0 IU/kg/day or <15 U/day.
• Untreated proliferative diabetic retinopathy.
• Blood Pressure: SBP >160 mmHg or DBP >100 mmHg.
• Measured glomerular filtration rate <80 mL/min/1.73m2 (using iohexol or calculated using the subject's measured serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI equation) or based on 24-hrs urine collection. Strict vegetarians (vegans) with a calculated GFR <70 mL/min/1.73m2 are excluded. The absolute (raw) GFR value will be used for subjects with body surface areas >1.73 m2.
• Presence or history of macroalbuminuria (>300 mg/g creatinine).
• Presence or history of panel-reactive anti-HLA antibodies above 30% or history/presence of donor specific anti-HLA antibodies in order to avoid unacceptable antigen(s) (Campbell PM 2007).
• For female subjects: Positive pregnancy test, presently breast-feeding, wishes to be pregnant at any time point in the future, which includes during or after the completion of the study even if study participation is ended early, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
• Presence or history of active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded even in the absence of clinical evidence of active infection.
• Known active alcohol or substance abuse.
• Severe co-existing cardiac disease
• Known hypercoagulative state.
• Symptomatic cholecystolithiasis.
• Acute or chronic pancreatitis.

Other protocol related inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Allogenic islet cells (human, U. Chicago)

Procedure: Intraportal infusion of islet cells; Intraportal infusion of islet cell through the portal vein in the liver.; Biological: Allogenic islet cells (human, U. Chicago); Human allogenic islet cells. Immunosuppression may include remicade, thymoglobulin,prograf, solu-medrol, and cellcept. Dosage will vary per patient based on weight. Patients will receive immunosuppression medications while islet cells are functioning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbAlc <7.0% and an absence of severe hypoglycemic events	The proportion of subjects with an HbAlc <7.0% at Day 365 AND free of severe hypoglycemic events from Day 28 to Day 365 inclusive following the first islet transplant.	1 year

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Piotr Witkowski, MD, PhD, University of Chicago

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Anticipated): May 1, 2025
• Study Completion (Anticipated): June 1, 2030

Study Registration Dates

• First Submitted: June 26, 2012
• First Submitted That Met QC Criteria: June 27, 2012
• First Posted (Estimate): June 28, 2012

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 11-0684