Pediatric Kidney Transplant Without Calcineurin Inhibitors

NCT ID: NCT00023231

Last Updated: 2016-10-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-02-28

Study Completion Date

2006-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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End-Stage Renal Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Daclizumab

Intervention Type DRUG

1 mg/kg/dose at study entry and Weeks 2, 4, 6, and 8

Methylprednisolone/prednisone

Intervention Type DRUG

Dosage is dependent on weight and varies throughout study. Refer to protocol for more information.

Mycophenolate mofetil

Intervention Type DRUG

Solution or oral tablet taken daily. Dosage depends on body surface area.

Sirolimus

Intervention Type DRUG

Oral tablet taken once prior to transplant. Dosage dependent on body surface area.

Bactrim

Intervention Type DRUG

Oral tablet taken three times per week. Dosage is dependent on weight.

Ganciclovir

Intervention Type DRUG

Oral tablet taken daily. Dosage is dependent on weight.

Lipitor

Intervention Type DRUG

Oral tablet taken daily

Interventions

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Daclizumab

1 mg/kg/dose at study entry and Weeks 2, 4, 6, and 8

Intervention Type DRUG

Methylprednisolone/prednisone

Dosage is dependent on weight and varies throughout study. Refer to protocol for more information.

Intervention Type DRUG

Mycophenolate mofetil

Solution or oral tablet taken daily. Dosage depends on body surface area.

Intervention Type DRUG

Sirolimus

Oral tablet taken once prior to transplant. Dosage dependent on body surface area.

Intervention Type DRUG

Bactrim

Oral tablet taken three times per week. Dosage is dependent on weight.

Intervention Type DRUG

Ganciclovir

Oral tablet taken daily. Dosage is dependent on weight.

Intervention Type DRUG

Lipitor

Oral tablet taken daily

Intervention Type DRUG

Other Intervention Names

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Zenapax Cellcept Rapamune

Eligibility Criteria

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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.
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Lauren Schenker

Rockville, Maryland, United States

Site Status

Countries

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United States

References

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Harmon W, Meyers K, Ingelfinger J, McDonald R, McIntosh M, Ho M, Spaneas L, Palmer JA, Hawk M, Geehan C, Tinckam K, Hancock WW, Sayegh MH. Safety and efficacy of a calcineurin inhibitor avoidance regimen in pediatric renal transplantation. J Am Soc Nephrol. 2006 Jun;17(6):1735-45. doi: 10.1681/ASN.2006010049. Epub 2006 May 10.

Reference Type RESULT
PMID: 16687625 (View on PubMed)

Iacomini J, Sayegh MH. Measuring T cell alloreactivity to predict kidney transplant outcomes: are we there yet? J Am Soc Nephrol. 2006 Feb;17(2):328-30. doi: 10.1681/ASN.2005121264. Epub 2005 Dec 28. No abstract available.

Reference Type RESULT
PMID: 16382014 (View on PubMed)

Schachter AD, Meyers KE, Spaneas LD, Palmer JA, Salmanullah M, Baluarte J, Brayman KL, Harmon WE. Short sirolimus half-life in pediatric renal transplant recipients on a calcineurin inhibitor-free protocol. Pediatr Transplant. 2004 Apr;8(2):171-7. doi: 10.1046/j.1399-3046.2003.00148.x.

Reference Type RESULT
PMID: 15049798 (View on PubMed)

Hoerning A, Koss K, Datta D, Boneschansker L, Jones CN, Wong IY, Irimia D, Calzadilla K, Benitez F, Hoyer PF, Harmon WE, Briscoe DM. Subsets of human CD4(+) regulatory T cells express the peripheral homing receptor CXCR3. Eur J Immunol. 2011 Aug;41(8):2291-302. doi: 10.1002/eji.201041095. Epub 2011 Jun 24.

Reference Type RESULT
PMID: 21538345 (View on PubMed)

Related Links

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https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT)

Other Identifiers

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CN01

Identifier Type: -

Identifier Source: secondary_id

DAIT CN01

Identifier Type: -

Identifier Source: org_study_id

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