Islet Transplantation for Type 1 Diabetes Mellitus

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00437398
• Collaborator: National Center for Research Resources (NCRR) (NIH)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 66
• Patients Per Site Per Month: 0

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Mellitus	Biological: Islet Transplant	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Islet Transplantation for Type 1 Diabetes Mellitus
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Islet Transplant Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets.	Biological: Islet Transplant; Purified pancreatic islets

Outcome Measures

Primary Outcome Measures

1. Mean Number of Hypoglycemic Events After Transplant [3, 6, 9, and 12 months since islet transplantation]

   Hypoglycemia is an abnormally diminished content of glucose in the blood.

Secondary Outcome Measures

1. Mean Glycated Hemoglobin (HbA1c) Since Transplant [3, 6, 9, and 12 months since islet transplantation]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Yogish C. Kudva, M.B.B.S., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Yogish C. Kudva, MBBS, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00437398
• Other Study ID Numbers: 06-003564; UL1RR024150
• First Posted: Feb 21, 2007
• Last Update Posted: Apr 25, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by Yogish C. Kudva, MBBS, Mayo Clinic: hypoglycemic unawareness
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from the Mayo Clinic in Rochester, Minnesota.
Pre-assignment Detail	Three subjects were screened for islet transplantation; one subject was ineligible, being Epstein-Barr virus (EBV) seronegative.

Arm/Group Title	Islet Transplant
Arm/Group Description	Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets.
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Islet Transplant
Arm/Group Description	Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets.
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The sample size (n=2) was too small to perform a meaningful analysis; therefore the data were not analyzed due to study termination.

Arm/Group Title	Islet Transplant
Arm/Group Description	Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets.
Measure Participants	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The sample size (n=2) was too small to perform a meaningful analysis; therefore the data were not analyzed due to study termination.

Arm/Group Title	Islet Transplant
Arm/Group Description	Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets.
Measure Participants	0

Adverse Events

Time Frame	Subjects were hospitalized for 48 hours for the transplant. They stayed close to hospital for 10-14 days for followup. Subjects were clinically evaluated every 3 months for the first year and annually thereafter.
Arm/Group Title	Islet Transplant
Arm/Group Description	Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets.
All Cause Mortality
	Islet Transplant
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Islet Transplant
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Blood and lymphatic system disorders
hemodynamic instability	1/2 (50%)	1
Infections and infestations
Hospitalization due to neutropenia and fever	1/2 (50%)	1
Other (Not Including Serious) Adverse Events
	Islet Transplant
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Endocrine disorders
Hypoglycemia	1/2 (50%)	2
Injury, poisoning and procedural complications
Mild change in liver function tests	1/2 (50%)	1

Limitations/Caveats

The study was terminated early due to difficulty in recruiting subjects, and ran short of funds. The sample size (n=2) was too small to perform a meaningful analysis.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.