Type 1 Diabetes Mellitus
Conditions
Keywords
hypoglycemic unawareness
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.
Interventions
BIOLOGICALIslet Transplant
Purified pancreatic islets
Sponsors
National Center for Research Resources (NCRR)
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Mayo Clinic in Rochester, Minnesota.
Pre-assignment details
Three subjects were screened for islet transplantation; one subject was ineligible, being Epstein-Barr virus (EBV) seronegative.
Participants by arm
| Arm | Count |
|---|---|
| Islet Transplant Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Islet Transplant |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 1 / 2 |
Outcome results
Primary
Mean Number of Hypoglycemic Events After Transplant
Hypoglycemia is an abnormally diminished content of glucose in the blood.
Time frame: 3, 6, 9, and 12 months since islet transplantation
Population: The sample size (n=2) was too small to perform a meaningful analysis; therefore the data were not analyzed due to study termination.
Secondary
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.
Time frame: 3, 6, 9, and 12 months since islet transplantation
Population: The sample size (n=2) was too small to perform a meaningful analysis; therefore the data were not analyzed due to study termination.