Diabetes Mellitus, Type 1
Conditions
Keywords
Islet Transplantation
Brief summary
The purpose of this study is to reverse hyperglycemia and insulin dependency, by islet cell transplantation, in patients with type 1 diabetes mellitus who have a stable kidney allograft.
Detailed description
1. To reverse hyperglycemia and insulin dependency by islet cell transplantation, in patients with Type 1 Diabetes Mellitus who have a stable kidney allograft; 2. To eliminate the incidence of hypoglycemic coma and unawareness by islet cell transplantation; 3. To assess long-term function of successful islet cell transplants; 4. To determine whether the natural history of the microvascular, macrovascular and neuropathic complications of Diabetes Mellitus are altered following successful transplantation of islet cells. 5. To assess the effect of exenatide to improve islet graft function and survival in subjects that demonstrate partial graft loss and have returned to using exogenous insulin. 6. To assess the ability of exenatide to improve islet survival at time of islet transplantation
Interventions
Islet Transplantation in subjects with a previous kidney transplant.
Sponsors
National Institutes of Health (NIH)
Health Resources and Services Administration (HRSA)
Diabetes Research Institute Foundation
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Rodolfo Alejandro
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Patients between 18 and 60 years of age. 2. Patients with type 1 diabetes mellitus. 3. Patients with a renal transplant that is more than 6 months old. 4. Patients with stable renal graft function for the preceding 6 months, i.e. no episodes of rejection and changes in serum creatinine no more than 0.5 mg/dl from baseline. 5. Patients who are taking tacrolimus, sirolimus +/- steroids for maintenance immunosuppression for at least 6 months and are tolerating levels satisfactory for islet transplantation without severe complications. 6. Patients with a body mass index (BMI) of less than or equal to 26.
Exclusion criteria
1. Stimulated or basal C-peptide \> 0.3 ng/ml. 2. Patients with unstable renal function - serum creatinine greater than 0.5 mg/dl above baseline. 3. Patients with proteinuria (albuminuria \> 300 mg in 24 hours +/- protein) of new onset since kidney transplantation. If proteinuria or albuminuria is thought to originate from the native kidney(s) this will not be an exclusion criterion. 4. Patients with corrected creatinine clearance of less than 40. 5. Patients weighing more than 80 kg. 6. Patients with a body mass index (BMI) of greater than 26. 7. Insulin requirement \> 1.0 U/kg/d. 8. Anemia (hemoglobin: males \< 11.0 g/dl; females \< 10.0 g/dl). 9. Abnormal liver function tests (consistently \> 1.5 x normal range). 10. Unstable diabetic retinopathy. 11. Evidence of acute or chronic active Epstein-Barr virus (EBV) infection (IgM ≥ IgG). Patients will be eligible if serological testing becomes consistent with previous exposure (i.e. IgG \> IgM). 12. Patients with history of malignancy or current malignancy other than non-melanomatous skin cancer, or finding of any lesions or symptoms during screening that are suspicious for malignancy, until properly investigated and ruled out. 13. Patients with elevation of prostate-specific antigen \> 4 unless malignancy has been excluded. 14. Patients with unstable cardiovascular status. 15. Patients with active infections until adequately treated, unless treatment is not judged as necessary by the investigators (including, but not limited to, mild skin and nail fungal infections). 16. Patients with serological evidence of infection with HIV, human t cell lymphotropic virus 1 (HTLV 1), HTLV 2, or hepatitis B (patients with serology consistent with previous vaccination and a history of vaccination are acceptable). 17. Patients with history and/or serological evidence of hepatitis C (those patients with hepatitis C, already transplanted in this protocol will continue in this trial). 18. Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis can be provided). 19. Patients with active peptic ulcer disease, gallstones, hepatic hemangioma, or portal hypertension. 20. Patients who are pregnant or breastfeeding, or who intend to procreate. 21. Patients who are sexually active females who are not: * post-menopausal, * surgically sterile, or * using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices combined with spermicidal gel are acceptable; condoms used alone are not acceptable). 22. Active alcohol or substance abuse; smoking in the last 6 months. 23. Patients with evidence of sensitization, i.e. panel reactive antibody (PRA) testing greater than 20%. 24. Lack of updated immunizations per current Centers for Disease Control (CDC) guidelines, as well as immunization against hepatitis B, pneumococcus, and influenza (during season), unless medically contraindicated. 25. Patients with psychogenic factors, which are judged at psychological evaluation, which make it unsafe to undergo islet transplantation, or which preclude therapeutic compliance. 26. Patients with any condition or any circumstance that would make it unsafe to undergo an islet transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Independence. | 1 year | Number of Participants who Achieved Insulin Independence at 1 Year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stimulated C-peptide Greater Than 0.5 ng/ml | 1 year | Partial graft function, as evidenced by basal C-peptide greater than 0.5 ng/ml |
| Reduction of Insulin Requirements | 1year | Reduction in insulin requirements in those patients who do not achieve insulin independence |
| Reduction in Severe Hypoglycemia, Improvement in Hypoglycemia Awareness | 1 years | Elimination or reduction in the incidence of hypoglycemic coma or unawareness |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Islet Transplantation Islet transplantation in subjects with previous kidney transplant | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Islet Transplantation |
|---|---|
| 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 | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 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 | 3 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 6 / 7 |
Outcome results
Primary
Insulin Independence.
Number of Participants who Achieved Insulin Independence at 1 Year
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplantation | Insulin Independence. | 2 Participants |
Secondary
Reduction in Severe Hypoglycemia, Improvement in Hypoglycemia Awareness
Elimination or reduction in the incidence of hypoglycemic coma or unawareness
Time frame: 1 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplantation | Reduction in Severe Hypoglycemia, Improvement in Hypoglycemia Awareness | 6 Participants |
Secondary
Reduction of Insulin Requirements
Reduction in insulin requirements in those patients who do not achieve insulin independence
Time frame: 1year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplantation | Reduction of Insulin Requirements | 4 Participants |
Secondary
Stimulated C-peptide Greater Than 0.5 ng/ml
Partial graft function, as evidenced by basal C-peptide greater than 0.5 ng/ml
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islet Transplantation | Stimulated C-peptide Greater Than 0.5 ng/ml | 6 Participants |