Islet Allotransplantation in Type 1 Diabetes

NCT01705899 | Suspended Phase 1 DMC

• 1 other identifier: IRB 2006H0200
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Islet transplantation can provide physiologic insulin replacement to patients with type 1 diabetes without the complications associated with whole pancreas transplantation. The purpose of this study is to achieve insulin-independence in patients with type 1 diabetes, thereby eliminating the need for exogenous insulin injections to maintain normal glucose levels, ameliorating severe hypoglycemia and potentially decreasing the development of diabetes-related complications. This study will investigate islet transplantation in subjects who have preserved renal function and subjects who have undergone cadaveric renal transplantation, since the latter subjects are already on immunosuppression. This is a single center, prospective trial of islet transplantation in subjects receiving islets alone or islets after kidney transplant. This is a phase I study investigating the use of islet transplantation for the treatment of type 1 diabetes. Subjects will be eligible for an islet transplant if they meet all of the inclusion criteria and none of the exclusion criteria outlined in the protocol. In brief, the aims of this study are to establish an islet transplant program at the Ohio State University, determine the safety of islet transplantation in islet alone and kidney transplant recipients, determine whether islet transplantation will reduce the frequency of severe hypoglycemic events, determine whether a novel steroid-free immunosuppressive protocol will prevent rejection in islet transplants and to achieve insulin independence at one year after the final islet transplant.

Conditions

Type 1 Diabetes

Keywords

Type 1 Diabetes; Islet transplant; Kidney transplant

Outcome Measures

Primary Outcomes (50)

• Incidence of adverse events

  Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

• Incidence of serious adverse events

  Serious adverse events will be defined (in accordance with FDA Title 21 CFR 312.32) as the following: * Death * Life-threatening and placing the subject at immediate risk of death * Hospitalization * Persistent or significant disability or incapacity * Congenital abnormal/birth defects * Requiring medical or surgical intervention to prevent permanent damage

  Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

• Incidence of infectious complications

  Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

• Incidence of procedural-related events

  Ex. Bleeding or portal vein thrombosis

  Day 1 post-transplant

• Incidence of elevated liver function tests

  Day 1 post-transplant

• Incidence of hypoglycemia

  Day 1 post-transplant

• Incidence of procedural-related events

  Ex. Bleeding or portal vein thrombosis

  Day 2 post-transplant

• Incidence of elevated liver function tests

  Day 2 post-transplant

• Incidence of hypoglycemia

  Day 2 post-transplant

• Incidence of procedural-related events

  Ex. Bleeding or portal vein thrombosis

  Day 3 post-transplant

• Incidence of elevated liver function tests

  Day 3 post-transplant

• Incidence of hypoglycemia

  Day 3 post-transplant

• Incidence of elevated liver function tests

  Day 5 post-transplant

• Incidence of hypoglycemia

  Day 5 post-transplant

• Incidence of elevated liver function tests

  Day 7 post-transplant

• Incidence of hypoglycemia

  Day 7 post-transplant

• Incidence of elevated liver function tests

  Day 10 post-transplant

• Incidence of hypoglycemia

  Day 10 post-transplant

• Incidence of elevated liver function tests

  Day 14 post-transplant

• Incidence of hypoglycemia

  Day 14 post-transplant

• Incidence of elevated liver function tests

  Day 21 post-transplant

• Incidence of hypoglycemia

  Day 21 post-transplant

• Incidence of abnormalities in lipids

  Day 28 post-transplant

• Incidence of elevated liver function tests

  Day 28 post-transplant

• Incidence of donor-specific antibody development

  Day 28 post-transplant

• Incidence of hypoglycemia

  Day 28 post-transplant

• Incidence of elevated liver function tests

  Day 42 post-transplant

• Incidence of hypoglycemia

  Day 42 post-transplant

• Incidence of elevated liver function tests

  Day 56 post-transplant

• Incidence of hypoglycemia

  Day 56 post-transplant

• Incidence of elevated liver function tests

  Day 90 post-transplant

• Incidence of hypoglycemia

  Day 90 post-transplant

• Incidence of abnormalities in lipids

  Day 90 post-transplant

• Incidence of donor-specific antibody development

  Day 90 post-transplant

• Incidence of elevated liver function tests

  Day 120 post-transplant

• Incidence of hypoglycemia

  Day 120 post-transplant

• Incidence of elevated liver function tests

  Day 180 post-transplant

• Incidence of hypoglycemia

  Day 180 post-transplant

• Incidence of abnormalities in lipids

  Day 180 post-transplant

• Incidence of donor-specific antibody development

  Day 180 post-transplant

• Incidence of elevated liver function tests

  Day 270 post-transplant

• Incidence of hypoglycemia

  Day 270 post-transplant

• Incidence of abnormalities in lipids

  Day 270 post-transplant

• Incidence of donor-specific antibody development

  Day 270 post-transplant

• Incidence of elevated liver function tests

  Day 365 post-transplant

• Incidence of abnormalities in lipids

  Day 365 post-transplant

• Incidence of hypoglycemia

  Day 365 post-transplant

• Incidence of donor-specific antibody development

  Day 365 post-transplant

• Change in microalbumin level

  Days 180 and 365 post-transplant

• Change in measured creatinine clearance

  Days 180 and 365 post-transplant

Secondary Outcomes (8)

• Amount of daily insulin units required

  Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

• Measurement of C-peptide

  Days 1, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

• Change in c-peptide level from fasting following administration of mixed meal

  Days 180 and 365 post-transplant

• Change in acute insulin response to glucose

  Days 180 and 365 post-transplant

• Incidence of blood glucose level <140mg/dl two hours after oral glucose tolerance tests

  Days 180 and 365 post-transplant

Study Arms (2)

Subjects with preserved kidney function

EXPERIMENTAL

Subjects with preserved renal function that have not previously received a kidney transplant will be treated with Human Pancreatic Islets (in the form of islets alone - IA).

Drug: Human Pancreatic Islets

Subjects with prior kidney transplant

EXPERIMENTAL

Subjects with renal failure secondary to diabetes who have received a prior kidney transplant at least 6 months previously and have stable renal function on a steroid-free immunosuppressive regimen will receive Human Pancreatic Islets (in the form of islets after kidney - IAK).

Drug: Human Pancreatic Islets

Interventions

Human Pancreatic Islets DRUG

Pancreatic islet tissue suspended in 150 - 300 ml of phenol red-free CMRL-1066 Transplant Media supplemented with 4% (w/v) HSA and 16mM HEPES in a 600ml transfer pack. Heparin will be administered at 70 IU/kg recipient body weight. Administered by intra-portal vein infusion. To be administered once, however, if full graft function is not achieved, a second or third dose of Pancreatic Islets may be given within 18 months of the first transplant.

Subjects with preserved kidney function; Subjects with prior kidney transplant

Eligibility Criteria

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

You may qualify if:

• Type 1 diabetes \> 5 years
• First islet transplant
• Demonstrate intensive efforts to manage diabetes for last 6 months (≥4 SMBG/day, ≥3 injections of insulin/day or use of pump and ≥3 contacts with diabetes care team in last 12 months)
• Metabolic complications: at least one of the following:
• Reduced hypoglycemia awareness (inability to sense hypoglycemia until blood glucose falls to \< 54 mg/dl or \> one hypoglycemic episode in last 12 months requiring outside help and not explained by clear precipitant)
• ≥2 severe hypoglycemic events or ≥2 hospitalizations for diabetic ketoacidosis (DKA) in last year.
• Ability to provide written informed consent
• Age 18-65
• Specific for group 2: All of above (1-6) with renal transplant at least 6 months previous

You may not qualify if:

• Age \< 18 years or \> 65 years
• Inability to provide informed consent
• Body Mass Index \> 29 kg/m2
• Insulin requirement of \> 50 units/day
• Stimulated C-peptide ≥ 0.2 ng/ml
• Current panel reactive anti-HLA antibodies \>20%
• Cardiovascular instability
• Previous islet transplant
• History of malignancy except squamous and basal cell skin cancer unless disease-free for \> 2 years determined by independent oncologist
• Active peptic ulcer disease
• Condition that may interfere with absorption of medications
• Hemoglobin A1C \> 12%
• Invasive aspergillus infection within one year
• Varicella titer index \<1.0
• Rubella titer \<10 IU/ml

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

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

Study Officials

• Amer Rajab, MD, PhD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2012
• First Posted: October 12, 2012
• Study Start: November 1, 2006
• Primary Completion (Estimated): October 1, 2033
• Study Completion (Estimated): October 1, 2033
• Last Updated: January 16, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)