Islet Cell Transplantation Alone and CD34+ Donor Bone Marrow Cell Infusion in Type 1 Diabetes Mellitus

March 29, 2017 updated by: Rodolfo Alejandro, University of Miami

Islet Cell Transplantation Alone and CD34+ Enriched Donor Bone Marrow Cell Infusion in Patients With Type 1 Diabetes Mellitus; Steroid Free Regimen

SPECIFIC AIMS:

  • To reverse hyperglycemia and insulin dependency in patients with Type 1 diabetes mellitus by islet cell transplantation.
  • To induce a state of donor specific tolerance and eliminate the need for continuous immunosuppressive therapy by simultaneous transplantation of donor bone marrow cells with islets and utilization of the monoclonal antibody Campath-1H for induction of Immunosuppression.
  • To assess long-term function of successful islet cell transplants in patients with Type 1 diabetes mellitus.
  • To determine whether the natural history of the microvascular, macrovascular and neuropathic complications are altered following successful transplantation of islet

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In our current protocol (IRB #2000/0024) the immunosuppressive regimen, comprised of induction with daclizumab and maintenance therapy with sirolimus and tacrolimus, has been combined with the infusion of CD34+ enriched donor bone marrow stem cells in an attempt to create a chimeric state and hence induce donor tolerance. This strategy was tested by evaluating graft survival following the removal of all immunosuppressive medication after one year.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • Diabetes Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients between 18 and 65 years of age
  2. Patients with type 1 diabetes mellitus for more than 5 years duration

  3. One or more of the following:

    • Hypoglycemia unawareness - judged by history of blood sugars <54 on glucometer without symptoms and/or hypoglycemic episodes requiring assistance from either family, glucagon administration or emergency services
    • Poor diabetes control (HbA1c>8% or >2 visits/yr to hospital for treatment of ketoacidosis) despite intensive insulin therapy
    • Progressive complications of type 1 diabetes mellitus
  4. Body Mass Index (BMI) ≤26

Exclusion Criteria:

  1. Untreated proliferative diabetic retinopathy;
  2. HbA1C > 12%;
  3. Insulin requirement > 1.0u/kg/d
  4. Stimulated or basal C-peptide > 0.3 ng/ml
  5. Creatinine clearance < 60 and/or serum creatinine consistently > 1.5mg/dl;
  6. Macroalbuminuria > 300mg albumin in 24 hours
  7. Presence of panel reactive antibodies > 20%;
  8. Previous/concurrent organ transplantation (except failed islet cell transplantation);
  9. Any medical condition requiring chronic use of steroids;
  10. Malignancy or previous malignancy (except non-melanomatous skin cancer);
  11. X-ray evidence of pulmonary infection;
  12. Active infections;
  13. Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis can be provided)
  14. Active peptic ulcer disease,
  15. Gall stones and/or portal hypertension and/or hemangioma on liver ultrasound;
  16. Serological evidence of HIV, HBV (HBsAg+ and/or HBcAb+ and/or HBsAb+ without evidence of vaccination), HTLV-1 or HCV;
  17. Negative serology for Epstein Barr virus (EBV) or evidence of acute infection (IgM>IgG);
  18. Abnormal liver function test;
  19. Anemia (hemoglobin <12.0 g/dl);
  20. Hyperlipidemia (fasting total cholesterol >240mg/dl and/or fasting triglycerides >200mg/dl and/or fasting LDL cholesterol>140mg/dl);
  21. Body Mass Index above 26 and/or weight >80kg;
  22. Prostate specific antigen (PSA) > 4 ng/ml;
  23. Unstable cardiovascular status (including positive stress echocardiography if >age 35);
  24. Active alcohol or substance abuse;
  25. Sexually active females who are not: a) post-menopausal, b) surgically sterile, or c) not using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices are acceptable; condoms used alone are not acceptable);
  26. Positive pregnancy test or intent for future pregnancy, or male subject's intent to procreate.
  27. Any condition or any circumstances that makes it unsafe to undergo an islet cell transplant.
  28. History of previous transplant or previous bone marrow infusion.
  29. Persistent leucopenia (white blood cell count <3,000/mm3

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Islet Transplantation and Bone Marrow
Administration of islets and infusion of CD34 enriched Bone Marrow cells in subjects with type 1 diabetes, impaired awareness of hypoglycemia and severe hypoglycemia.
Biological: Islet Transplantation and Bone Marrow
Islet transplantation and CD34 Bone Marrow infusion in subjects with type 1 diabetes.
Other Names:
  • Islet
  • type 1 DM
  • Bone marrow

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The Achievement of Persistent Islet Function Following Cessation of Immunosuppression.
Time Frame: for the duration of islet graft function
Immunosuppression was never discontinued. Patients elected to move to other trials to receive additional islet infusions. Since immunosuppression was never discontinued we were not able to evaluate the primary endpoint.
for the duration of islet graft function
A Reduction or Absence of Rejection Episodes
Time Frame: for the duration of islet graft function
Number of rejection episodes after transplantation. Immunosuppression was never discontinued. Patients elected to move to other trials to receive additional islet infusions. Since immunosuppression was never discontinued we were not able to evaluate the primary endpoint.
for the duration of islet graft function

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Subjects With Basal C-peptide Greater Than 0.5 ng/ml
Time Frame: for the duration of islet graft function
Number of subjects with basal C-peptide greater than 0.5 ng/ml prior to weaning of immunosuppression;
for the duration of islet graft function
Number of Subjects With Reduction of Severe Hypoglycemia and Improvement in Hypoglycemia Awareness
Time Frame: for the duration of islet graft function
Number of subjects with reduction of episodes of severe hypoglycemia and the presence of awareness of hypoglycemia
for the duration of islet graft function

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Miami

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Diabetes Research Institute Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rodolfo Alejandro, MD, Diabetes Research Institute University of Miami

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2000

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 14, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 14, 2006

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 18, 2006

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 4, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 29, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2000/0024
  • R01DK056953 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Single arm few subjects.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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