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Islet Transplantation for Type 1 Diabetes Mellitus

Primary Purpose

Type 1 Diabetes Mellitus

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Islet Transplant
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring hypoglycemic unawareness

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Duration of diabetes: 5 years or more
  • Type 1 diabetes with C-peptide < 200 pmol/L and a simultaneous plasma glucose between 60 and 250 mg/dl
  • Complex insulin program supervised by an endocrinologist for at least 6 months
  • Hypoglycemic unawareness diagnosed using Clarke Awareness Questionnaire
  • Body weight < 70 kg
  • Body Mass Index < 30 kg/m^2
  • Insulin requirement < 40 units/day by multiple daily injections or < 30 units /day by external insulin pump or < 0.6 unit/kg/day with a HbA1c < 7.0 % ( Normal < 6 %)
  • No overt cardiovascular disease
  • No laser treatment for retinopathy
  • Retinopathy diagnosed by ophthalmologist to be stable and requiring no further evaluation for at least one year
  • Women of child bearing age will have a negative pregnancy test at screening and time of trial initiation
  • Women enrolled in the trial should be willing to practice birth control while on immunosuppression
  • No psychologic issues that would interfere with adherence to safe clinical practice
  • Blood type (ABO) compatibility
  • No evidence of chronic liver disease (aspartate aminotransferase (AST) < 2.5 times normal, alanine aminotransferase (ALT) < 2.5 times normal, international normalized ratio (INR) < 1.4, No evidence of fatty liver on abdominal ultrasound.

Exclusion Criteria:

  • Ongoing infection
  • Ongoing alcohol or drug abuse
  • Clinical portal hypertension
  • Gall stones
  • Liver hemangioma on ultrasound interfering with islet infusion
  • Lack of updated immunization

  • Unstable cardiovascular status as defined by:

    1. Myocardial infarction/acute coronary syndrome in last year
    2. Significant coronary atherosclerosis on angiography
    3. Active ischemia at evaluation
  • Pre-trial low-density lipoprotein (LDL) cholesterol > 100 and triglycerides > 200 mg/dl with or without lipid lowering therapy
  • Active peptic ulcer disease
  • Previous organ transplantation except islet transplantation
  • Negative serology for Epstein-Barr Virus (EBV) or ongoing acute EBV infection

  • Previous malignancy unless

    1. 5 years ago
    2. basal cell cancer
    3. squamous cell cancer
  • Requiring steroid therapy for any reason
  • Positive Purified Protein Derivative (PPD - Tuberculosis Skin Test)
  • Serological evidence of HIV, Hepatitis C or Hepatitis B
  • Chronic anemia
  • Single Antigen B (SAB) normalized value >1500

  • Renal disease

    1. Iothalamate clearance < 70 cc/min
    2. 24 hour urine protein > 500 mg/24 hours

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Islet Transplant

Arm Description

Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets.

Outcomes

Primary Outcome Measures

Mean Number of Hypoglycemic Events After Transplant
Hypoglycemia is an abnormally diminished content of glucose in the blood.

Secondary Outcome Measures

Mean Glycated Hemoglobin (HbA1c) Since Transplant
HbA1c is a lab test that shows the average level of blood sugar (glucose) over the previous 3 months. It shows how well the subject is controlling his/her diabetes.

Full Information

First Posted
February 20, 2007
Last Updated
April 18, 2013
Sponsor
Mayo Clinic
Collaborators
National Center for Research Resources (NCRR)
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1. Study Identification

Unique Protocol Identification Number
NCT00437398
Brief Title
Islet Transplantation for Type 1 Diabetes Mellitus
Official Title
Islet Transplantation for Type 1 Diabetes Mellitus
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated early due to difficulty in recruiting subjects, and ran short of funds.
Study Start Date
July 2006 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
National Center for Research Resources (NCRR)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The complex program of insulin replacement for type 1 diabetes that is current clinical standard of care is difficult to implement for long periods of time, associated with an increased risk of severe hypoglycemia and implemented by less than 50 % of the population of such patients. Outcomes of transplantation of isolated human islets have substantially improved and been performed at about 40 institutions around the world. We are proposing a clinical phase 1/phase 2 study of islet transplantation alone evaluating safety and efficacy in five patients with type 1 diabetes. Islet isolation from deceased donor pancreases will be performed at the Mayo Rochester Islet Isolation facility and islets infused by Interventional Radiology into the portal venous system. Following islet infusion, patients will be hospitalized for 48 hours in the General Clinical Research Center (GCRC) or at the Rochester Methodist Hospital. Multiple safety and efficacy outcomes will be followed on multiple occasions during the first year and periodically thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus
Keywords
hypoglycemic unawareness

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Islet Transplant
Arm Type
Experimental
Arm Description
Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets.
Intervention Type
Biological
Intervention Name(s)
Islet Transplant
Intervention Description
Purified pancreatic islets
Primary Outcome Measure Information:
Title
Mean Number of Hypoglycemic Events After Transplant
Description
Hypoglycemia is an abnormally diminished content of glucose in the blood.
Time Frame
3, 6, 9, and 12 months since islet transplantation
Secondary Outcome Measure Information:
Title
Mean Glycated Hemoglobin (HbA1c) Since Transplant
Description
HbA1c is a lab test that shows the average level of blood sugar (glucose) over the previous 3 months. It shows how well the subject is controlling his/her diabetes.
Time Frame
3, 6, 9, and 12 months since islet transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Duration of diabetes: 5 years or more Type 1 diabetes with C-peptide < 200 pmol/L and a simultaneous plasma glucose between 60 and 250 mg/dl Complex insulin program supervised by an endocrinologist for at least 6 months Hypoglycemic unawareness diagnosed using Clarke Awareness Questionnaire Body weight < 70 kg Body Mass Index < 30 kg/m^2 Insulin requirement < 40 units/day by multiple daily injections or < 30 units /day by external insulin pump or < 0.6 unit/kg/day with a HbA1c < 7.0 % ( Normal < 6 %) No overt cardiovascular disease No laser treatment for retinopathy Retinopathy diagnosed by ophthalmologist to be stable and requiring no further evaluation for at least one year Women of child bearing age will have a negative pregnancy test at screening and time of trial initiation Women enrolled in the trial should be willing to practice birth control while on immunosuppression No psychologic issues that would interfere with adherence to safe clinical practice Blood type (ABO) compatibility No evidence of chronic liver disease (aspartate aminotransferase (AST) < 2.5 times normal, alanine aminotransferase (ALT) < 2.5 times normal, international normalized ratio (INR) < 1.4, No evidence of fatty liver on abdominal ultrasound. Exclusion Criteria: Ongoing infection Ongoing alcohol or drug abuse Clinical portal hypertension Gall stones Liver hemangioma on ultrasound interfering with islet infusion Lack of updated immunization Unstable cardiovascular status as defined by: Myocardial infarction/acute coronary syndrome in last year Significant coronary atherosclerosis on angiography Active ischemia at evaluation Pre-trial low-density lipoprotein (LDL) cholesterol > 100 and triglycerides > 200 mg/dl with or without lipid lowering therapy Active peptic ulcer disease Previous organ transplantation except islet transplantation Negative serology for Epstein-Barr Virus (EBV) or ongoing acute EBV infection Previous malignancy unless 5 years ago basal cell cancer squamous cell cancer Requiring steroid therapy for any reason Positive Purified Protein Derivative (PPD - Tuberculosis Skin Test) Serological evidence of HIV, Hepatitis C or Hepatitis B Chronic anemia Single Antigen B (SAB) normalized value >1500 Renal disease Iothalamate clearance < 70 cc/min 24 hour urine protein > 500 mg/24 hours
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yogish C. Kudva, M.B.B.S.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Links:
URL
http://clinicaltrials.mayo.edu
Description
Mayo Clinic Clinical Trials

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Islet Transplantation for Type 1 Diabetes Mellitus

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