AzTrials
AzTrials

Diabetes Mellitus, Insulin-DependentPhase 2NCT00014911

Islet Transplantation for Type 1 Diabetes

A Phase 2 study testing Islet Transplantation, Sirolimus and Tacrolimus in people with Diabetes Mellitus, Insulin-Dependent, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Diabetes Mellitus, Insulin-Dependent
What is being tested?
Islet Transplantation, Sirolimus and Tacrolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
9 sitesin 5 countries
Study dates
Apr 2001to Aug 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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 virus, hepatitis B virus, human immunodeficiency virus (HIV), or Tuberculosis (TB) (or under treatment for suspected TB).
Show all 22Show fewer
  • Have a history of malignancy, except squamous or basal skin cancer.
  • Weigh more than 70 kilograms or have a Body Mass Index (BMI) greater than 26 kg/m^2 at time of screening.
  • Have a C-peptide value of 0.3 ng/ml or more following a 5.0 gram intravenous arginine infusion challenge.
  • 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-human leukocyte antigen (HLA) antibody.
  • Have an insulin requirement of more that 0.7 International Units (IU)/kilograms/day.
  • Have a blood glycosylated hemoglobin (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).

Trial locations and contacts

9 sites in 5 countries.

9 sites in 5 countries

United States5 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Miami

    Miami, Florida, 33136

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Benaroya Research Institute at Virginia Mason Research Center

    Seattle, Washington, 98101

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

Canada1 site

  • University of Alberta

    Edmonton, Alberta

Other trials in Canada

Germany1 site

  • Justus-Leibig University

    Giessen, 35385

Other trials in Germany

Italy1 site

  • University of Milan

    Milan

Other trials in Italy

Switzerland1 site

  • University of Geneva

    Geneva

Other trials in Switzerland

About this study

Official title: Islet Transplantation for Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression (ITN005CT)

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.

Read the detailed description

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 determine 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 last islet transplantation. Additional follow-up may be provided at least annually for up to 9 years post first transplantation.

Being tested
Islet Transplantation, Sirolimus, Tacrolimus, Daclizumab, Sulfamethoxazole
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Islet TransplantationProcedure or surgery

    Participants will receive portal vein islet infusions (up to 3), e.g., islet transplantations, with a targeted total of exceeding 10,000 islet equivalents per kilogram of body weight (IE/kg) per infusion. Up to three transplants are possible depending on individual results.

  • SirolimusDrug

    Administered at a dose of 0.2 mg/kg by mouth once pre-transplantation then 0.1 mg/kg daily post-transplantation. Dosing will be adjusted to achieve a trough peripheral blood level of 12-15 ng/mL x3 months after transplantation and 7-12 ng/mL for the remainder of the study.

  • TacrolimusDrug

    Administered at a dose of 1 mg by mouth once pre-transplantation followed by 1 mg twice daily post transplantation. Levels will be adjusted to achieve a peripheral blood trough level of 3-6 ng/mL for maintenance immunosuppression.

  • DaclizumabDrug

    Administered at a dose of 1 mg/kg intravenously immediately pre-transplantation and 2, 4, 6, and 8 weeks post-transplantation, totaling 5 doses(over 8 weeks). Further daclizumab dosing may be necessary based on individual results and islet transplantation needs.

  • SulfamethoxazoleDrug

    An antibacterial used to prevent opportunistic infections

  • GanciclovirDrug

    An antiviral used to kill viruses and stop viral replication

  • TrimethoprimDrug

    An antibacterial used to prevent opportunistic infections

  • PentamidineDrug

    An antiprotozoal used to prevent disease

Study groups in NCT00014911
Study groupRoleWhat they receive
Islet TransplantationExperimentalAll study participants
Receives: Procedure: Islet Transplantation; Drug: Sirolimus; Drug: Tacrolimus; Drug: Daclizumab; Drug: Sulfamethoxazole; Drug: Ganciclovir; Drug: Trimethoprim; Drug: Pentamidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent of Participants That Achieved Insulin Independence With Adequate Control of Blood Glucose Levels at One Year Post Final Islet Transplantation.

    Insulin independence: exogenous insulin not required and glycemic control is achieved as defined by maintaining 1.) a blood glycosylated hemoglobin (HbA1c) level < 6.5% (Normal:<5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher),2) a blood glucose level after an overnight fast not exceeding 140 mg per deciliter (dL) more than three times in any week (Normal: 70 to 120 mg/dL), and 3)not exceeding a 2-hour postprandial blood glucose level of 180 mg/dL more than four times per week (Normal: <140mg/dL if <=50 years of age, <150 mg/dL for ages 50-60 years and <160 mg/dL for ages 60+)

    Measured: One year status post participant receipt of final islet transplantation

Secondary outcomes (3)

  1. Percent of Participants With Partial Islet Function One Year Post Final Islet Transplantation.

    Partial islet function definition: a fasting basal C-peptide level >= 0.3 ng/mL and a continuing need for insulin or suboptimal glycemic control (Note: C-peptide is a substance that the pancreas releases into the bloodstream in equal amounts to insulin, thereby showing how much insulin the body is making). Adequate glycemic control is defined by: 1) a blood HbA1c level <6.5%, 2) a blood glucose level after an overnight fast not exceeding 140 mg/dL more than three times in any week and, 3) a 2-hour postprandial blood glucose level not exceeding 180 mg/dL more than four times per week

    Measured: One year post receipt of final islet transplantation

  2. Percent of Participants That Achieved Insulin Independence From First Transplant

    Insulin independence: exogenous insulin not required and glycemic control is achieved as defined by maintaining 1) a blood glycosylated hemoglobin (HbA1c) level < 6.5% (Normal:<5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher),2) a blood glucose level after an overnight fast not exceeding 140 mg per deciliter (dL) more than three times in any week (Normal: 70 to 120 mg/dL), and 3)not exceeding a 2-hour postprandial blood glucose level of 180 mg/dL more than four times per week (Normal: <140mg/dL if <=50 years of age, <150 mg/dL for ages 50-60 years and <160 mg/dL for ages 60+)

    Measured: First transplantation until end of study (up to six years post final transplantation)

  3. Percent of Participants With Detectable Fasting Basal C-Peptide Levels

    C-peptide is a substance that the pancreas releases into the bloodstream in equal amounts to insulin, thereby showing how much insulin the body is making. C-peptide secretion is used to measure the function of transplanted islets. Higher levels indicate better islet function. Detectable fasting basal levels of C-peptide secretion are >=0.3 ng/ml.

    Measured: Two years post first transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Study startApr 2001
  3. Primary completionJun 2005
  4. Study completionAug 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00014911
Sponsor's protocol ID
DAIT ITN005CT (DAIT NIS01)
Status last verified
Feb 2017
First submitted
13 Apr 2001
Last updated
15 Mar 2017
Individual data sharing
Yes: Data access is provided to the public in : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) portal.

Publications

  • 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. doi: 10.1056/NEJMoa061267.

    PubMed 17005949

  • Brennan DC, Shannon MB, Koch MJ, Polonsky KS, Desai N, Shapiro J. Portal vein thrombosis complicating islet transplantation in a recipient with the Factor V Leiden mutation. Transplantation. 2004 Jul 15;78(1):172-3. doi: 10.1097/01.tp.0000128332.71657.ea. No abstract available.

    PubMed 15257060

  • Benedini S, Ermetici F, Briganti S, Codella R, Terruzzi I, Maffi P, Caldara R, Secchi A, Nano R, Piemonti L, Alejandro R, Ricordi C, Luzi L. Insulin-mimetic effects of short-term rapamycin in type 1 diabetic patients prior to islet transplantation. Acta Diabetol. 2018 Jul;55(7):715-722. doi: 10.1007/s00592-018-1141-z. Epub 2018 Apr 13.

    PubMed 29654388

  • Gala-Lopez B, Kin T, O'Gorman D, Pepper AR, Senior P, Humar A, Shapiro AM. Microbial contamination of clinical islet transplant preparations is associated with very low risk of infection. Diabetes Technol Ther. 2013 Apr;15(4):323-7. doi: 10.1089/dia.2012.0297. Epub 2013 Feb 25.

    PubMed 23438305

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Islet Transplantation, Sirolimus and Tacrolimus in people with Diabetes Mellitus, Insulin-Dependent, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Canada, Germany, Italy, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Oct 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent of Participants That Achieved Insulin Independence With Adequate Control of Blood Glucose Levels at One Year Post Final Islet Transplantation. (time frame: One year status post participant receipt of final islet transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00014911, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in