Diabetes Mellitus, Type I
Conditions
Keywords
Type I diabetes, Islet after Kidney Transplant, Islet transplantation
Brief summary
The purpose of the study is to learn if islet transplantation is an effective treatment for Type 1 diabetes in people who have had a kidney transplant. The primary objectives of the study are: \- To set up islet transplantation in patients who have had a kidney transplant and who are using an immunosuppressive regimen that works The Secondary objective of the study is: * To find out if successful islet transplantation leads to improved metabolic control and reduced renal complication from diabetes
Detailed description
Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2doses of basiliximab. All patients will receive Etanercept to promote engraftment.
Interventions
BIOLOGICALPurified Pancreatic Islets
Islet after kidney transplant in patients with type I diabetes.
DRUGEtanercept
Given as induction for islet cell transplant
Sponsors
Boston Area Diabetes Endocrinology Research Center (funded by NIDDK)
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects * Age 18 to 70 years of age * Have insulin dependent Diabetes Mellitus Type 1 * Are post-renal transplant on maintenance immunosuppression with stable renal function * HbA1c \> 7.5% or \< 7.5% and hypoglycemia unawareness
Exclusion criteria
* Weight more than 90 kg * Insulin requirement \> 60 Units/day * Other (non-kidney) organ transplants except prior failed pancreatic graft. * Untreated or unstable proliferative diabetic retinopathy * Presence of de novo antibody production since the renal allograft or either Class I or Class II panel-reactive anti-HLA antibodies * Active infection * Negative screen for Epstein-Barr virus (EBV) * Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin * History of Factor V Leiden mutation * Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g. warfarin) after transplantation (low-dose aspirin treatment is allowed) or subjects with international normalized ratio (INR) \> 1.5 * Severe co-existing cardiac disease * Persistent elevation of liver function tests at the time of study entry * Acute or chronic pancreatitis * Male subjects with elevation of prostate specific antigen * Pregnancy * Positive screen for polyoma (BK) virus * Untreated hyperlipidemia * Recent hemorrhagic stroke * Factors associated with an increased risk of bleeding Contact PI for complete Incl-Excl criteria list.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Insulin Independence With Both an HbA1c ≤ 6.5% and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant or a Reduction in HbA1c of at Least 1 Point and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant. | 1 year after the subject's first islet transplant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Decrease in HbA1c | 1 year after subject's first islet transplant | Subjects will have a decrease in HbA1c of at least \>1% |
| Stable or Decrease in Urinary Albumin and Creatinine Ratio and Serum Creatinine | 1 year after subjects initial islet transplant | Proteinuria and serum creatinine will be stable or decreased as compared to pre-transplant values |
| An Absence Cardiovascular Events, Cerebral Vascular Accident, and Myocardial Infarction | 1 year after the subject's first islet transplant | — |
| Impact on Vision | 1 year after the subject's first islet transplant | Improvement of frequency of interventions and from changes in reported visual acuity with optical refraction and severity of diabetic retinopathy |
| Absence of Negative Renal Impact Measures | 1 year after the subject's first islet transplant | Loss of allograft survivial (return to dialysis, retransplant, death) and Renal allograft function meausred by SCr |
| Improvement of Metabolic Control | 1 year after the subject's first islet transplant | Whether there is an improvement in metabolic control in IAK will be evaluated based on improvement in 1. basal c-peptide levels, 2. MMTT, 3. insulin requirements, and 4. c-peptide to glucose, creatinine ratio (CPGCR). |
| Number of Participants With a Decrease of Severe Hypoglycemic Events | 1 year after subject's first transplant | Subjects will have a decrease in severe hypoglycemic events |
| Reduction of Insulin Requriements | 1 year after the subject's first islet transplant | Evidence of partial success will be considered for subjects who have a reduction in insulin requirements but who are not insulin independent. This will be assessed by comparing the pre-transplant insulin requirement expressed as insulin units per kg per day with the requirement preceding subsequent islet transplants and the insulin requirements at 6 months and 1, 2, and 3 years after the first and last transplant. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Islet Transplant Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence.
For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft.
Induction therapy for subsequent transplants will be 2 doses of basiliximab.
All patients will receive Etanercept to promote engraftment.
Purified Pancreatic Islets: Islet after kidney transplant in patients with type I diabetes.
Etanercept: Given as induction for islet cell transplant | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Islet Transplant |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 3 / 4 |
Outcome results
Primary
Insulin Independence With Both an HbA1c ≤ 6.5% and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant or a Reduction in HbA1c of at Least 1 Point and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant.
Time frame: 1 year after the subject's first islet transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Islet Transplant | Insulin Independence With Both an HbA1c ≤ 6.5% and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant or a Reduction in HbA1c of at Least 1 Point and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant. | 4 participants |
Secondary
Absence of Negative Renal Impact Measures
Loss of allograft survivial (return to dialysis, retransplant, death) and Renal allograft function meausred by SCr
Time frame: 1 year after the subject's first islet transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplant | Absence of Negative Renal Impact Measures | 4 Participants |
Secondary
An Absence Cardiovascular Events, Cerebral Vascular Accident, and Myocardial Infarction
Time frame: 1 year after the subject's first islet transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplant | An Absence Cardiovascular Events, Cerebral Vascular Accident, and Myocardial Infarction | 4 Participants |
Secondary
Impact on Vision
Improvement of frequency of interventions and from changes in reported visual acuity with optical refraction and severity of diabetic retinopathy
Time frame: 1 year after the subject's first islet transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplant | Impact on Vision | 2 Participants |
Secondary
Improvement of Metabolic Control
Whether there is an improvement in metabolic control in IAK will be evaluated based on improvement in 1. basal c-peptide levels, 2. MMTT, 3. insulin requirements, and 4. c-peptide to glucose, creatinine ratio (CPGCR).
Time frame: 1 year after the subject's first islet transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplant | Improvement of Metabolic Control | 4 Participants |
Secondary
Number of Participants With a Decrease in HbA1c
Subjects will have a decrease in HbA1c of at least \>1%
Time frame: 1 year after subject's first islet transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplant | Number of Participants With a Decrease in HbA1c | 4 Participants |
Secondary
Number of Participants With a Decrease of Severe Hypoglycemic Events
Subjects will have a decrease in severe hypoglycemic events
Time frame: 1 year after subject's first transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplant | Number of Participants With a Decrease of Severe Hypoglycemic Events | 4 Participants |
Secondary
Reduction of Insulin Requriements
Evidence of partial success will be considered for subjects who have a reduction in insulin requirements but who are not insulin independent. This will be assessed by comparing the pre-transplant insulin requirement expressed as insulin units per kg per day with the requirement preceding subsequent islet transplants and the insulin requirements at 6 months and 1, 2, and 3 years after the first and last transplant.
Time frame: 1 year after the subject's first islet transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplant | Reduction of Insulin Requriements | 4 Participants |
Secondary
Stable or Decrease in Urinary Albumin and Creatinine Ratio and Serum Creatinine
Proteinuria and serum creatinine will be stable or decreased as compared to pre-transplant values
Time frame: 1 year after subjects initial islet transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplant | Stable or Decrease in Urinary Albumin and Creatinine Ratio and Serum Creatinine | 4 Participants |