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Pediatric Kidney Transplant Without Calcineurin Inhibitors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00023231
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : October 21, 2016
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
End-Stage Renal Disease Drug: Daclizumab Drug: Methylprednisolone/prednisone Drug: Mycophenolate mofetil Drug: Sirolimus Drug: Bactrim Drug: Ganciclovir Drug: Lipitor Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Calcineurin Inhibitor Sparing Protocol in Living Donor Pediatric Kidney Transplantation
Study Start Date : February 2001
Actual Primary Completion Date : August 2004
Actual Study Completion Date : August 2006

Resource links provided by the National Library of Medicine

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 Name: Zenapax

Drug: Methylprednisolone/prednisone
Dosage is dependent on weight and varies throughout study. Refer to protocol for more information.
Other Name: 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 Name: 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

Primary Outcome Measures :
  1. Efficacy of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment [ Time Frame: Throughout study ]
  2. Adverse effects of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment, especially hypertension, serious infections and chronic nephrotoxicity [ Time Frame: Throughout study ]

Secondary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00023231

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United States, Maryland
Lauren Schenker
Rockville, Maryland, United States, 20850
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Additional Information:
Publications of Results:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00023231     History of Changes
Other Study ID Numbers: DAIT CN01
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: October 21, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Additional relevant MeSH terms:
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Kidney Failure, Chronic
Renal Insufficiency, Chronic
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Trimethoprim, Sulfamethoxazole Drug Combination
Ganciclovir triphosphate
Calcineurin Inhibitors
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anti-Bacterial Agents