Pediatric Kidney Transplant Without Calcineurin Inhibitors

October 19, 2016 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Calcineurin Inhibitor Sparing Protocol in Living Donor Pediatric Kidney Transplantation

The purpose of this study is to see the effect of using drugs other than calcineurin inhibitors to improve the rate of kidney transplant failure.

Kidney transplantation can help children with end-stage kidney disease. However, it has been difficult to find treatment for donor graft rejection that does not have a lot of side effects. Researchers hope to find treatments (immunosuppressants) with fewer side effects. One approach is to avoid using calcineurin inhibitors and to try a new drug known as sirolimus instead. Another is to use steroids less often. This study will test whether using sirolimus, fewer steroid treatments, MMF, and certain antibodies will improve long-term graft survival in children receiving kidney transplants from living donors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Renal transplantation is widely recognized as the treatment of choice for children with end-stage renal disease (ESRD). Although outcomes of renal transplantation in children have improved during the past decade, success has been limited by both non-specific tolerance and the complications associated with immunosuppressants. Steroids and calcineurin inhibitors have the most toxic side effects. Use of sirolimus for immunosuppression has not been associated with as many complications. Recent studies from Europe have demonstrated that sirolimus can be combined with MMF and steroids to provide excellent graft survival in the absence of calcineurin inhibitors. Steroid side-effects can be lessened by tapering the steroid dose to an every-other-day schedule. This protocol tests whether immunosuppression by IL-2r antibody, sirolimus, MMF, and alternate-day steroids will provide comparable graft survival for living donor recipients, compared to current immunosuppression, but with reduced complications of calcineurin inhibitors.

Evaluations prior to transplantation include a complete history and physical examination, CBC, liver function tests, and antibodies for CMV, EBV, HIV, HbsAG, and HCV. All appropriate vaccinations are provided before transplantation. Transplant recipients receive immunosuppression therapy using antibody induction (daclizumab), corticosteroids, mycophenolate mofetil, and sirolimus. Serum sirolimus levels are measured so that doses can be adjusted to maintain certain blood levels of the drug. Bactrim and ganciclovir are given for infection prophylaxis. If the patient has consistent high levels of fasting cholesterol, treatment with lipitor may be given. A transplant biopsy is performed at the time of the transplant and at 3, 6, and 12 months post transplantation and at times when a rejection is suspected. A radionuclide GFR is done at the same time points, and at 1, 24, and 36 months. The protocol biopsies, blood, and urine samples will be analyzed by genomic methods to determine differences in gene expression post transplantation. In the event of a first acute rejection, patients are treated with Solu-Medrol for 3 consecutive days. A second rejection (at the discretion of the transplant center) or severe rejection (Banff Grade 3) is treated with antibody therapy and, after a second or severe rejection, the immunosuppressant regimen is changed. Patients are followed for 36 months with routine physical examinations and laboratory assessments.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Not Applicable

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
    • Maryland
      • Rockville, Maryland, United States, 20850
        • Lauren Schenker

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

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Patients may be eligible for this study if they:

  • Are 21 years of age and under.
  • Are kidney recipients of living-donor grafts, except when living-donor grafts are identically matched.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Are recipients of identical (HLA matched) living-donor grafts.
  • Are recipients of cadaver-donor grafts.
  • Have certain abnormal kidney diseases that may return.
  • Have failed 2 or more previous kidney transplants.
  • Have fat abnormalities that are inherited or present at high levels.

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
Intervention / Treatment
Experimental: 1
Participants will receive immunosuppression therapy using antibody induction (daclizumab), corticosteroids, mycophenolate mofetil, and sirolimus prior to transplantation. Bactrim and ganciclovir will be taken for infection prophylaxis. If the participant has consistent high levels of fasting cholesterol, treatment with lipitor may be given.
Drug: Daclizumab
1 mg/kg/dose at study entry and Weeks 2, 4, 6, and 8
Other Names:
  • Zenapax
Drug: Methylprednisolone/prednisone
Dosage is dependent on weight and varies throughout study. Refer to protocol for more information.
Other Names:
  • Cellcept
Drug: Mycophenolate mofetil
Solution or oral tablet taken daily. Dosage depends on body surface area.
Drug: Sirolimus
Oral tablet taken once prior to transplant. Dosage dependent on body surface area.
Other Names:
  • Rapamune
Drug: Bactrim
Oral tablet taken three times per week. Dosage is dependent on weight.
Drug: Ganciclovir
Oral tablet taken daily. Dosage is dependent on weight.
Drug: Lipitor
Oral tablet taken daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment
Time Frame: Throughout study
Throughout study
Adverse effects of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment, especially hypertension, serious infections and chronic nephrotoxicity
Time Frame: Throughout study
Throughout study

Secondary Outcome Measures

Outcome Measure
Time Frame
Immune inhibition detected by sensitive and specific assays (including intragraft and peripheral monitoring) for expression patterns of activation and effector function markers
Time Frame: Throughout study
Throughout study

Collaborators and Investigators

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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

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

February 1, 2001

Primary Completion (Actual)

August 1, 2004

Study Completion (Actual)

August 1, 2006

Study Registration Dates

First Submitted

August 29, 2001

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Estimate)

October 21, 2016

Last Update Submitted That Met QC Criteria

October 19, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAIT CN01
  • CN01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: SDY131
    Information comments: ImmPort study identifier is SDY131
  2. Study Protocol
    Information identifier: SDY131
    Information comments: ImmPort study identifier is SDY131
  3. Study summary, -design,-demographics, -mechanistic assays, -files et al.
    Information identifier: SDY131
    Information comments: ImmPort study identifier is SDY131

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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