Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00006505
Status:
COMPLETED
Last Update Posted:
2021-04-20
First Post:
2000-11-17
Brief Title:
Solitary Islet Transplantation for Type 1 Diabetes Mellitus Using Steroid Sparing Immunosuppression
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Solitary Islet Transplantation for Type 1 Diabetes Mellitus Using Steroid Sparing Immunosuppression
Status:
COMPLETED
Status Verified Date:
2021-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will test whether a new islet transplant procedure will enable patients with type 1 diabetes mellitus to stop insulin therapy Islets are cell clusters in the pancreas that contain insulin-producing cells The new procedure features three important advances first developed by a group in Edmonton Canada over the way islet transplants have traditionally been performed 1 the islets are transplanted immediately after they are removed from the donor 2 islets are transplanted from two different donors in order to obtain the number of islets in a normal pancreas and 3 the anti-rejection drug regimen is designed to reduce the harmful side effects of conditioning chemotherapy In the standard transplant procedure patients receive intensive chemotherapy following the transplant This study will use no radiation and lower-dose chemotherapy
Patients between the ages of 18 and 65 with the diagnosis of type 1 diabetes mellitus for at least 5 years may be eligible for this study Candidates will be screened with a medical history and physical examination blood tests chest X-ray and tuberculin skin test electrocardiogram and exercise test for heart function abdominal ultrasound psychological evaluation and an arginine stimulated c-peptide test The latter test determines if the patient is producing any insulin Eligibility is restricted to patients who make no insulin at all
The study has an active phase lasting 15 months and follow-up that continues indefinitely Patients will receive 10000 islet equivalents per kilogram 22 pounds of body weight This will likely require two separate transplant procedures from two donors Before the first surgery patients will be given anti-rejection immune suppressing drugs including FK506 and rapamycin orally and daclizumab intravenously The islets will be infused through a tube placed in the portal vein the large vein that feeds the liver After surgery patients will receive insulin intravenously for 24 hours They will then have an abdominal ultrasound and blood tests to determine liver function If fewer than 10000 islets were transplanted patients will continue insulin treatment with the dosages adjusted to account for the transplanted islets They will take Daclizumab every 2 weeks and FK506 and rapamycin daily Blood tests to follow how much of these drugs are in the blood stream will be performed daily at first and then weekly after blood levels of these drugs stabilize They will be given antibiotics to prevent infections The arginine test will be repeated 2 weeks after the transplant and periodically thereafter Blood will be drawn weekly to check drug levels and monthly for other tests The investigators will track daily insulin requirements and these will be recorded monthly
Patients who require a second transplant to achieve the required amount of islets will return for the procedure when a compatible organ is donated The second procedure will be done as described above As before insulin will be infused for 24 hours following surgery It will then be stopped however and will not be resumed unless blood glucose levels reach above 180 milligramsdeciliter Patients will continue taking FK506 and rapamycin indefinitely Daclizumab will be given every 2 weeks for 4 doses following the second transplant and then stopped Patients will take an antiviral called ganciclovir for 14 weeks and another antibiotic for 1 year following surgery For the first year after surgery patients will have frequent blood tests to monitor drug levels and immune function They will return to NIH for a complete history and physical examination 2 and 3 years after the final islet transplant and will be contacted yearly by phone to ascertain their general health status and whether they remain insulin independent
Patients between the ages of 18 and 65 with the diagnosis of type 1 diabetes mellitus for at least 5 years may be eligible for this study Candidates will be screened with a medical history and physical examination blood tests chest X-ray and tuberculin skin test electrocardiogram and exercise test for heart function abdominal ultrasound psychological evaluation and an arginine stimulated c-peptide test The latter test determines if the patient is producing any insulin Eligibility is restricted to patients who make no insulin at all
The study has an active phase lasting 15 months and follow-up that continues indefinitely Patients will receive 10000 islet equivalents per kilogram 22 pounds of body weight This will likely require two separate transplant procedures from two donors Before the first surgery patients will be given anti-rejection immune suppressing drugs including FK506 and rapamycin orally and daclizumab intravenously The islets will be infused through a tube placed in the portal vein the large vein that feeds the liver After surgery patients will receive insulin intravenously for 24 hours They will then have an abdominal ultrasound and blood tests to determine liver function If fewer than 10000 islets were transplanted patients will continue insulin treatment with the dosages adjusted to account for the transplanted islets They will take Daclizumab every 2 weeks and FK506 and rapamycin daily Blood tests to follow how much of these drugs are in the blood stream will be performed daily at first and then weekly after blood levels of these drugs stabilize They will be given antibiotics to prevent infections The arginine test will be repeated 2 weeks after the transplant and periodically thereafter Blood will be drawn weekly to check drug levels and monthly for other tests The investigators will track daily insulin requirements and these will be recorded monthly
Patients who require a second transplant to achieve the required amount of islets will return for the procedure when a compatible organ is donated The second procedure will be done as described above As before insulin will be infused for 24 hours following surgery It will then be stopped however and will not be resumed unless blood glucose levels reach above 180 milligramsdeciliter Patients will continue taking FK506 and rapamycin indefinitely Daclizumab will be given every 2 weeks for 4 doses following the second transplant and then stopped Patients will take an antiviral called ganciclovir for 14 weeks and another antibiotic for 1 year following surgery For the first year after surgery patients will have frequent blood tests to monitor drug levels and immune function They will return to NIH for a complete history and physical examination 2 and 3 years after the final islet transplant and will be contacted yearly by phone to ascertain their general health status and whether they remain insulin independent
Detailed Description:
We will test whether pancreatic islets isolated from cadaveric human donor pancreata can be
transplanted into the portal vein of patients with type 1 diabetes mellitus T1DM in such a way so as to achieve insulin independence for the recipient The protocol will employ a defined islet isolation procedure percutaneous islet infusion into the recipient s portal vein via an intra-portal catheter tight glycemic control during the peri-transplant period and a novel immunosuppressive protocol that avoids glucocorticoids Up to 20 patients between the ages of 18 and 65 who have been diagnosed with T1DM for at least five years and who have no detectable endogenous insulin producing capacity will be enrolled Since the study calls for at least 10000 islet equivalents IEQs per kilogram recipient body weight to be transplanted and since a typical human pancreas yields approximately 20 to 40 times 105 IEQs most protocol enrollees will require islets isolated from two different donors Islets will be transplanted shortly after isolation and since human donor pancreata are available at unpredictable times the timing of the islet transplant procedure will also be unpredictable The study s primary end-point will be insulin independence at one year following the transplantation of at least 10000 IEQs per kilogram recipient body weight Secondary endpoints will be evidence of partial islet function as reflected by stimulated c-peptide secretion a Hgb A1c of 70 or less and the absence of severe hypoglycemia Additional secondary endpoints will be to determine 1 if any immune parameters are predictive of islet loss 2 if islet transplantation has any effect on renal function and 3 if the protocol influences fasting lipid profiles
transplanted into the portal vein of patients with type 1 diabetes mellitus T1DM in such a way so as to achieve insulin independence for the recipient The protocol will employ a defined islet isolation procedure percutaneous islet infusion into the recipient s portal vein via an intra-portal catheter tight glycemic control during the peri-transplant period and a novel immunosuppressive protocol that avoids glucocorticoids Up to 20 patients between the ages of 18 and 65 who have been diagnosed with T1DM for at least five years and who have no detectable endogenous insulin producing capacity will be enrolled Since the study calls for at least 10000 islet equivalents IEQs per kilogram recipient body weight to be transplanted and since a typical human pancreas yields approximately 20 to 40 times 105 IEQs most protocol enrollees will require islets isolated from two different donors Islets will be transplanted shortly after isolation and since human donor pancreata are available at unpredictable times the timing of the islet transplant procedure will also be unpredictable The study s primary end-point will be insulin independence at one year following the transplantation of at least 10000 IEQs per kilogram recipient body weight Secondary endpoints will be evidence of partial islet function as reflected by stimulated c-peptide secretion a Hgb A1c of 70 or less and the absence of severe hypoglycemia Additional secondary endpoints will be to determine 1 if any immune parameters are predictive of islet loss 2 if islet transplantation has any effect on renal function and 3 if the protocol influences fasting lipid profiles
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-DK-0036 | None | None | None |