End-Stage Renal DiseaseNCT00023231
Pediatric Kidney Transplant Without Calcineurin Inhibitors
A study testing Daclizumab, Methylprednisolone/prednisone and Mycophenolate mofetil in people with End-Stage Renal Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- End-Stage Renal Disease
- What is being tested?
- Daclizumab, Methylprednisolone/prednisone and Mycophenolate mofetil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2001to Aug 2006
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- End-Stage Renal Disease
- Being tested
- Daclizumab, Methylprednisolone/prednisone, Mycophenolate mofetil, Sirolimus, Bactrim
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaclizumabDrug
Also called Zenapax
1 mg/kg/dose at study entry and Weeks 2, 4, 6, and 8
Methylprednisolone/prednisoneDrug
Also called Cellcept
Dosage is dependent on weight and varies throughout study. Refer to protocol for more information.
Solution or oral tablet taken daily. Dosage depends on body surface area.
SirolimusDrug
Also called Rapamune
Oral tablet taken once prior to transplant. Dosage dependent on body surface area.
BactrimDrug
Oral tablet taken three times per week. Dosage is dependent on weight.
GanciclovirDrug
Oral tablet taken daily. Dosage is dependent on weight.
LipitorDrug
Oral tablet taken daily
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 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. Receives: Drug: Daclizumab; Drug: Methylprednisolone/prednisone; Drug: Mycophenolate mofetil; Drug: Sirolimus; Drug: Bactrim; Drug: Ganciclovir; Drug: Lipitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment
Measured: Throughout study
Adverse effects of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment, especially hypertension, serious infections and chronic nephrotoxicity
Measured: Throughout study
Secondary outcomes (1)
Immune inhibition detected by sensitive and specific assays (including intragraft and peripheral monitoring) for expression patterns of activation and effector function markers
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study startFeb 2001
- Primary completionAug 2004
- Study completionAug 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for End-Stage Renal DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00023231
- Sponsor's protocol ID
- DAIT CN01
- Other IDs
- CN01
- Status last verified
- Oct 2016
- First submitted
- 29 Aug 2001
- Last updated
- 21 Oct 2016
- Results posted
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 16687625Iacomini 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.
PubMed 16382014Schachter 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.
PubMed 15049798Hoerning 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.
PubMed 21538345
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Calcineurin Inhibitor Sparing Protocol in Living Donor Pediatric Kidney Transplantation
- ClinicalTrials.gov ID
- NCT00023231
- Acronym / sponsor ID
- DAIT CN01
- Conditions
- End-Stage Renal Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Feb 2001
- Primary completion
- Aug 2004 (actual)
- Study completion
- Aug 2006 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Daclizumab, Drug: Methylprednisolone/prednisone, Drug: Mycophenolate mofetil, Drug: Sirolimus, Drug: Bactrim, Drug: Ganciclovir, Drug: LipitorParticipants 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. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Are 21 years of age and under.
- Are kidney recipients of living-donor grafts, except when living-donor grafts are identically matched.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaclizumabAlso: Zenapax1 mg/kg/dose at study entry and Weeks 2, 4, 6, and 8 | Drug | 1 |
| Methylprednisolone/prednisoneAlso: CellceptDosage is dependent on weight and varies throughout study. Refer to protocol for more information. | Drug | 1 |
| Mycophenolate mofetilSolution or oral tablet taken daily. Dosage depends on body surface area. | Drug | 1 |
| SirolimusAlso: RapamuneOral tablet taken once prior to transplant. Dosage dependent on body surface area. | Drug | 1 |
| BactrimOral tablet taken three times per week. Dosage is dependent on weight. | Drug | 1 |
| GanciclovirOral tablet taken daily. Dosage is dependent on weight. | Drug | 1 |
| LipitorOral tablet taken daily | Drug | 1 |
Primary outcome
Efficacy of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment
Time frame: 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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2016.
- Results publication: PubMed 16687625Harmon 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.
- Results publication: PubMed 16382014Iacomini 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.
- Results publication: PubMed 15049798Schachter 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.
- Results publication: PubMed 21538345Hoerning 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.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Daclizumab, Methylprednisolone/prednisone and Mycophenolate mofetil in people with End-Stage Renal Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment (time frame: Throughout study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00023231, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2016.