Islet Transplantation in Patients With "Brittle" Type I Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Chicago
Sponsor:
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT01630850
First received: June 26, 2012
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
Diabetes Mellitus, Type 1
Biological: Allogenic islet cells (human, U. Chicago)
Procedure: Intraportal infusion of islet cells

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Islet Transplantation in Patients With "Brittle" Type I Diabetes

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • HbAlc <7.0% and an absence of severe hypoglycemic events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 10
Study Start Date: May 2012
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allogenic islet cells (human, U. Chicago) 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.
Procedure: Intraportal infusion of islet cells
Intraportal infusion of islet cell through the portal vein in the liver.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  • 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.
  • 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.
  • At least one episode of severe hypoglycemia in 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.
  • HbAlc>10%.
  • 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, 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01630850

Contacts
Contact: Lindsay Schenck, RN, BSN 773-702-2504 Lschenck@surgery.bsd.uchicago.edu
Contact: Piotr Witkowski, MD, PhD (773) 702-2447 pwitkowski@surgery.bsd.uchicago.edu

Locations
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Lindsay Schenck, RN, BSN    773-702-2504    Lschenck@surgery.bsd.uchicago.edu   
Principal Investigator: Piotr Witkowski, MD, PhD         
Sponsors and Collaborators
University of Chicago
Investigators
Principal Investigator: Piotr Witkowski, MD, PhD University of Chicago
  More Information

No publications provided

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT01630850     History of Changes
Other Study ID Numbers: 11-0684
Study First Received: June 26, 2012
Last Updated: July 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014