Miami, Florida 33136

  • Dependent

Purpose:

The purpose of this study is to test whether the islet cell transplantation procedures and results from a previous study in Edmonton, Canada, can be repeated. The study also is designed to learn more about diabetes control using islet cell transplantation. This is a Phase I/II study (a study that examines effectiveness and looks for side effects). The transplanting of islet cells has been studied in Type 1 diabetic patients whose blood sugar levels will not stay normal, despite intensive insulin therapy. A recent study conducted in Edmonton, Canada, was able to demonstrate that islet transplantation led to insulin independence in a majority of the patients treated. This study extends the results obtained from the Edmonton study, which used islet transplantation in Type 1 diabetic patients with steroid-free immunosuppression.


Study summary:

This is a Phase I/II study (a study that examines effectiveness and looks for side effects). The transplanting of islet cells has been studied in Type 1 diabetic patients whose blood sugar levels will not stay normal, despite intensive insulin therapy. A recent study conducted in Edmonton, Canada, was able to demonstrate that islet transplantation led to insulin independence in a majority of the patients treated. This study extends the results obtained from the Edmonton study, which used islet transplantation in Type 1 diabetic patients with steroid-free immunosuppression. Eligible patients were randomly selected from the total pool of people who applied through the Immune Tolerance Network. Patients will receive at least 10,000 "islet equivalents" per kilogram (2.2 pounds) of body weight. This likely will require 2 separate islet infusions from 2 separate donors. Immediately before the first transplant, patients will be given anti-rejection (immune suppressing) drugs, including tacrolimus and sirolimus (orally) and daclizumab (intravenously). The islets will be infused into the liver through a tube placed in the portal vein. Heparin (a medication to prevent blood clots) will be administered with the islet infusion. A longer-acting form of heparin will also be given by daily injections during the next week after each transplant. After surgery, patients will receive insulin intravenously for 24 hours. Patients will have an abdominal ultrasound and blood tests to determine liver function. If fewer than 10,000 islets were transplanted, patients will continue insulin treatment, with the dosages adjusted if necessary to account for the transplanted islets. They will take daclizumab every 2 weeks for 8 weeks and tacrolimus and sirolimus daily. Patients will be given antibiotics to prevent infections. Blood tests to see how much immunosuppressant drug is in the blood will be performed until the drug is at a stable level. Periodically there will be tests to see if the islet cells are functioning. Blood will be drawn to check drug levels and for other tests routinely. Daily insulin requirements will be checked, and these will be recorded monthly. Patients will be followed for at least 1 year post final transplant. Additional follow-up may be provided at least annually for up to 5 years.


Criteria:

Inclusion Criteria Patients may be eligible for this study if they: - Have had Type 1 diabetes mellitus for more than 5 years, and are exhibiting 1 of the following, despite intensive insulin management efforts: a) hypoglycemic unawareness, as defined by inability to sense hypoglycemia until the blood glucose falls to less than 54 mg/dl; b) metabolic instability, with 2 or more episodes of severe hypoglycemia (defined as an event with symptoms consistent with hypoglycemia in which the patient requires the assistance of another person and which is associated with a blood glucose below 54 mg/dl) or 2 or more hospital visits for diabetic ketoacidosis over the last year; or c) despite efforts at optimal glucose control, progressive secondary complications of diabetes as defined by retinopathy, nephropathy, or neuropathy. - Are 18 to 65 years of age. Exclusion Criteria Patients will not be eligible for this study if they: - Have had severe cardiac disease as defined by: a) recent myocardial infarction within the past 6 months; b) angiographic evidence of non-correctable coronary artery disease; or c) evidence of ischemia on a functional cardiac exam. - Actively abuse alcohol or substances, including cigarette smoking (must not have smoked within the last 6 months). - Have psychiatric problems that prevent them from being a suitable candidate for transplantation (such as schizophrenia, bipolar disorder, or major depression that is not controlled or stable on current medication). - Have a history of not following prescribed regimens. - Have active infection including hepatitis C, hepatitis B, HIV, or TB (or under treatment for suspected TB). - Have a history of malignancy, except squamous or basal skin cancer. - Weigh more than 70 kg or have a BMI greater than 26 kg/m2 at time of screening. - Have a C-peptide value of 0.3 ng/ml or more following a 5.0 gram intravenous arginine infusion. - Are unable to provide informed consent. - Have gallstones or hemangioma in liver. - Have untreated proliferative retinopathy. - Are breast-feeding or pregnant, or intend to try and become pregnant (females) or to father a child (males), or fail to follow birth control methods. - Have had a previous transplant, or evidence of anti-HLA antibody. - Have an insulin requirement of more that 0.7 IU/kg/day. - Have an HbA1c higher than 12 percent. - Are unable to reach the hospital for transplantation within 2 hours of notification. - Have untreated or treated hyperlipidemia. - Have a medical condition requiring chronic use of steroids. - Use coumadin or other anticoagulants (aspirin is allowed). - Have Addison's disease. - Have a negative screen for Epstein-Barr virus (EBV).


Study is Available At:


Original ID:

DAIT NIS01 (ITN005CT)


NCT ID:

NCT00014911


Secondary ID:


Study Acronym:


Brief Title:

Islet Cell Transplants for Diabetes


Official Title:

Islet Transplantation for Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression (ITN005CT - NIS01)


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

65 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institute of Allergy and Infectious Diseases (NIAID)


Oversight Authority:

United States: Federal Government


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Intervention Model: Single Group Assignment, Mask


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

40


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:James Shapiro
Principal Investigator

Study Dates

Start Date:April 2001
Completion Date:August 2010
Completion Type:Actual
Primary Completion Date:June 2005
Primary Completion Type:Actual
Verification Date:March 2011
Last Changed Date:March 2, 2011
First Received Date:April 13, 2001

Study Outcomes

Outcome Type:Primary Outcome
Measure:Insulin independence at one year post-transplant
Time Frame:At 2 weeks, and 1, 3, 6 and 12 months following final transplant
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Partial graft function
Time Frame:At 2 weeks, and 1, 3, 6 and 12 months following final transplant, but more or fewer assessments are
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Stimulated C-peptide greater than 0.5 mg/ml
Time Frame:At 2 weeks, and 1, 3, 6 and 12 months following final transplant, but more or fewer assessments are
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:HbA1c less than 6.5%
Time Frame:At 2 weeks, and 1, 3, 6 and 12 months following final transplant, but more or fewer assessments are
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Absence of hypoglycemic coma/unawareness
Time Frame:At 2 weeks, and 1, 3, 6 and 12 months following final transplant, but more or fewer assessments are
Safety Issues:False

Study Interventions

Intervention Type:Procedure
Name:Islet cells infusion
Description:A target total of greater than or equal to 10,000 IE (islet equivalent) per kilogram of the recipient's body weight will be infused into the portal vein with a precutaneous tranhepatic catheter. Up to three transplants are possible depending on individual results.
Arm Name:A
Intervention Type:Drug
Name:Sirolimus
Description:Administered orally at a loading dose of 0.2 mg/kg daily, immediately pre-transplant and continued at a dose of 0.1 mg/kg daily each morning. Three months after the most recent transplant the dose will be changed to 12-15ng/mL. After three months following the last transplant the dose will again change to 7-10 ng/mL.
Arm Name:A
Intervention Type:Drug
Name:Tacrolimus
Description:Administered orally at a dose of 1 mg, given immediately before transplantation, and continued at a dose of 1 mg twice daily. When possible the dose will be changed to 3-6ng/mL and will remain at this level for the remainder of the study.
Arm Name:A
Intervention Type:Drug
Name:Daclizumab
Description:Administered at a dose of 1 mg/kg via peripheral IV and given immediately before transplantation.Additionally administered at weeks 2, 4, 6, and 8 following transplantation, totaling 5 doses (over 8 weeks). Further daclizumab dosing may be necessary based on individual results and transplantation needs.
Arm Name:A
Intervention Type:Drug
Name:Sulfamethoxazole
Description:An antibacterial used to prevent opportunistic infections
Arm Name:A
Intervention Type:Drug
Name:Ganciclovir
Description:An antiviral used to kill viruses and stop viral replication
Arm Name:A
Intervention Type:Drug
Name:Trimethoprim
Description:An antibacterial used to prevent opportunistic infections
Arm Name:A
Intervention Type:Drug
Name:Pentamidine
Description:An antiprotozoal used to prevent disease
Arm Name:A

Study Arms

Study Arm Type:Experimental
Arm Name:A
Description:All study participants

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Institute of Allergy and Infectious Diseases (NIAID)
Agency Class:Other
Agency Type:Collaborator
Agency Name:Immune Tolerance Network (ITN)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation:Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, Secchi A, Brendel MD, Berney T, Brennan DC, Cagliero E, Alejandro R, Ryan EA, DiMercurio B, Morel P, Polonsky KS, Reems JA, Bretzel RG, Bertuzzi F, Froud T, Kandaswamy R, Sutherland DE, Eisenbarth G, Segal M, Preiksaitis J, Korbutt GS, Barton FB, Viviano L, Seyfert-Margolis V, Bluestone J, Lakey JR. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006 Sep 28;355(13):1318-30.
PMID:17005949

Data Source: ClinicalTrials.gov

Date Processed: September 23, 2021

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