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Pediatric Kidney Transplant Without Calcineurin Inhibitors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00023231
First received: August 29, 2001
Last updated: October 19, 2016
Last verified: October 2016
  Purpose

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 Intervention
End-Stage Renal Disease
Drug: Daclizumab
Drug: Methylprednisolone/prednisone
Drug: Mycophenolate mofetil
Drug: Sirolimus
Drug: Bactrim
Drug: Ganciclovir
Drug: Lipitor

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Calcineurin Inhibitor Sparing Protocol in Living Donor Pediatric Kidney Transplantation

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Efficacy of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Adverse effects of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment, especially hypertension, serious infections and chronic nephrotoxicity [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: February 2001
Study Completion Date: August 2006
Primary Completion Date: August 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00023231

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

Additional Information:
Publications:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: SDY131
ImmPort study identifier is SDY131
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: SDY131
ImmPort study identifier is SDY131
Study summary, -design,-demographics, -mechanistic assays, -files et al.  This link exits the ClinicalTrials.gov site
Identifier: SDY131
ImmPort study identifier is SDY131

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00023231     History of Changes
Other Study ID Numbers: DAIT CN01  CN01 
Study First Received: August 29, 2001
Last Updated: October 19, 2016
Health Authority: United States: Federal Government
Individual Participant Data  
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:
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Prednisolone acetate
Methylprednisolone acetate
Prednisone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Sirolimus
Everolimus
Mycophenolic Acid
Trimethoprim, Sulfamethoxazole Drug Combination
Mycophenolate mofetil
Daclizumab
Ganciclovir
Atorvastatin Calcium
Ganciclovir triphosphate
Calcineurin Inhibitors
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on December 02, 2016