Kidney Failure, ChronicPhase 1NCT00768729
Safety of Immunosuppression Minimization in Children and Adolescents After Kidney Transplantation
A Phase 1 study testing Sirolimus and MMF or Azathioprine in people with Kidney Failure, Chronic and Kidney Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
Trial summary
Kidney transplantation is widely considered to be the treatment of choice for children with End Stage Renal Disease (ESRD). The purpose of this study is to determine the safety of sirolimus monotherapy for long-term immunosuppression in children and adolescents after kidney transplantation. Read more about this study
- Who is it for?
- Ages 1 year to 20 years
- Conditions the study is for
- Kidney Failure, Chronic, Kidney Transplantation, Immunosuppression
- What is being tested?
- Sirolimus and MMF or Azathioprine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 5 sitesUnited States
- Study dates
- May 2009to Dec 2012
- Phase
- Phase 1
- 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 1 year to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participant and/or parent guardian able to understand and willing to provide informed consent
- Previously enrolled and completed the CCTPT-PC01 study and within the 36 months post-completion timeframe prior to study entry
- Currently receiving sirolimus and MMF or azathioprine therapy
- No history of acute rejection episodes
- No evidence of acute or chronic rejection on the 24 month CCTPT-PC01 protocol biopsy or any subsequent biopsy obtained after that time prior to study entry
- PRA (Class I and II) less than 5% at study entry
Show all 10Show fewer
- No evidence of donor specific antibody at study entry
- Stable renal function with GFR greater than 60 cc/min 1.73M^2 using the Schwartz calculated method
- A negative pregnancy test for female participants of childbearing potential at study entry
- Agreement by female and male participants to use FDA approved methods of contraception.
Who cannot join
- Total lymphocyte count less than 400 mm^3
- Acute or chronic infection at study entry
- Treatment with investigational drug within 1 month prior to study entry
- Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the study
- History of allergic reaction to Iodine GFR assay
- History of malignancy within the past 12 months
- Inability or unwillingness to give informed consent or comply with the study protocol
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Children's Hospital, Boston
Boston, Massachusetts
Children's Hospital of Central California
Madera, California
Children's Hospital, Philadelphia
Philadelphia, Pennsylvania
UCSF Children's Hospital
San Francisco, California
Children's Hospital and Regional Medical Center, Seattle
Seattle, Washington
About this study
Official title: Immunosuppression Minimization to Single Drug Therapy With Sirolimus (Rapamune) in Pediatric Transplantation
Kidney transplantation is widely considered to be the treatment of choice for children with End Stage Renal Disease (ESRD). The purpose of this study is to determine the safety of sirolimus monotherapy for long-term immunosuppression in children and adolescents after kidney transplantation.
Read the detailed description
Improvements in surgical techniques, donor selection, immunosuppression practices, and the enhanced experience of specialized pediatric transplant teams have all led to marked improvements in patient and kidney graft survival in infants and young children Long-term graft survival rates decrease in adolescents 11 to 17 years of age. Several studies have suggested this decrease may be the result of noncompliance with immunosuppressive medications in this age group. Therefore, protocols that minimize the use of immunosuppressive medications, while retaining kidney function are necessary for improving graft and patient survival in children. The purpose of this study is to determine the safety of sirolimus monotherapy for long-term immunosuppression in children and adolescents after kidney transplantation.
This study will enroll 10 participants who previously completed the CCTPT-PC01 study. The accrual period is scheduled for 12 months. The study follow-up period will last 96 weeks. Patients from the CCTPT-PC01 study have been maintained on sirolimus and mycophenolate mofetil (MMF) since 2-3 months post transplant. Enrolled participants receiving (MMF) or Azathioprine at study entry will have their doses withdrawn gradually over a period of 6 months. Dosage will be reduced by 25% initially and by 25% every 2 months resulting in complete withdrawal by 6 months.
This study will consist of 11 study visits after screening and study entry. Study visits will occur at weeks 1, 8, 16, 24, 32, 40, 48, 60, 72, 84, and 96. A physical exam, vital signs, sirolimus levels, as well as blood and urine collection will occur at all visits. A renal biopsy will be performed at week 96.
- Being tested
- Sirolimus, MMF or Azathioprine
- Keywords
- End stage renal disease, Kidney transplantation, Renal transplantation, Kidney failure, Children, Adolescents, Sirolimus, Rapamycin, CellCept, Mycophenolate mofetil (MMF), Azathioprine
- Medical subject headings
- Kidney Failure, Chronic, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin, Rapamune
Oral tablets or liquid taken every 12 hours. Dosage adjusted to attain target trough levels of 8-12 ng/mL. Participants who have maintained such levels at study entry on once daily dosage will be permitted to continue on once daily dosing.
MMF or AzathioprineDrug
600 mg/m2 MMF taken orally daily or Azathioprine orally daily. Dosage of Azathioprine is dependent on weight. MMF or Azathioprine will be reduced by 25% initially and by 25% every 2 months resulting in complete withdrawal by 6 months.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants who have been maintained on MMF at study entry will start the study on 600 mg/m2 MMF orally daily. Participants who have been maintained on Azathioprine due to MMF intolerance will receive 1 mg/kg Azathioprine orally daily.
Participants will continue receiving sirolimus throughout the study. However, MMF or Azathioprine will be withdrawn gradually over a period of at least 6 months. Dosage will be reduced by 25% initially and by 25% every subsequent 2 months resulting in complete withdrawal by 6 months. Receives: Drug: Sirolimus; Drug: MMF or Azathioprine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Per-person incidence of acute rejection episodes and death or graft loss
Measured: Throughout study
Secondary outcomes (11)
Incidence of chronic allograft dysfunction
Measured: Throughout study
Incidence of sub-clinical rejection
Measured: Throughout study
Incidence of hospitalizations
Measured: Throughout study
Incidence of surgical complications
Measured: Throughout study
Resumption of MMF or other therapy
Measured: Throughout study
Incidence, severity, and treatment of anemia, hypertension, hyperlipidemia, proteinuria, thrombocytopenia, and leukopenia
Measured: Throughout study
Incidence, severity, and treatment of opportunistic infections
Measured: Throughout study
Incidence of biopsy proven PTLD
Measured: Throughout study
Renal function assessed by measured GFR
Measured: At baseline, week 48 and week 96
Development of donor-specific or non-specific anti-HLA antibodies
Measured: Throughout study
Evolution of immune response in cellular, humoral, and molecular assays from baseline through week 96
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 posted8 Oct 2008 (estimated)
- Study startMay 2009
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Kidney Failure, ChronicStudies 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 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- William H. Harmon, MD, Study chair, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00768729
- Sponsor's protocol ID
- DAIT CTOTC-01
- Status last verified
- Feb 2013
- First submitted
- 6 Oct 2008
- Last updated
- 15 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
McDonald RA, Smith JM, Ho M, Lindblad R, Ikle D, Grimm P, Wyatt R, Arar M, Liereman D, Bridges N, Harmon W; CCTPT Study Group. Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. Am J Transplant. 2008 May;8(5):984-9. doi: 10.1111/j.1600-6143.2008.02167.x.
PubMed 18416737Watson CJ, Bradley JA, Friend PJ, Firth J, Taylor CJ, Bradley JR, Smith KG, Thiru S, Jamieson NV, Hale G, Waldmann H, Calne R. Alemtuzumab (CAMPATH 1H) induction therapy in cadaveric kidney transplantation--efficacy and safety at five years. Am J Transplant. 2005 Jun;5(6):1347-53. doi: 10.1111/j.1600-6143.2005.00822.x.
PubMed 15888040
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunosuppression Minimization to Single Drug Therapy With Sirolimus (Rapamune) in Pediatric Transplantation
- ClinicalTrials.gov ID
- NCT00768729
- Acronym / sponsor ID
- DAIT CTOTC-01
- Keywords
- End stage renal disease, Kidney transplantation, Renal transplantation, Kidney failure, Children, Adolescents, Sirolimus, Rapamycin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- May 2009
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 8 Oct 2008 (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.
Kidney transplantation is widely considered to be the treatment of choice for children with End Stage Renal Disease (ESRD). The purpose of this study is to determine the safety of sirolimus monotherapy for long-term immunosuppression in children and adolescents after kidney transplantation.
Detailed description
Improvements in surgical techniques, donor selection, immunosuppression practices, and the enhanced experience of specialized pediatric transplant teams have all led to marked improvements in patient and kidney graft survival in infants and young children Long-term graft survival rates decrease in adolescents 11 to 17 years of age. Several studies have suggested this decrease may be the result of noncompliance with immunosuppressive medications in this age group. Therefore, protocols that minimize the use of immunosuppressive medications, while retaining kidney function are necessary for improving graft and patient survival in children. The purpose of this study is to determine the safety of sirolimus monotherapy for long-term immunosuppression in children and adolescents after kidney transplantation.
This study will enroll 10 participants who previously completed the CCTPT-PC01 study. The accrual period is scheduled for 12 months. The study follow-up period will last 96 weeks. Patients from the CCTPT-PC01 study have been maintained on sirolimus and mycophenolate mofetil (MMF) since 2-3 months post transplant. Enrolled participants receiving (MMF) or Azathioprine at study entry will have their doses withdrawn gradually over a period of 6 months. Dosage will be reduced by 25% initially and by 25% every 2 months resulting in complete withdrawal by 6 months.
This study will consist of 11 study visits after screening and study entry. Study visits will occur at weeks 1, 8, 16, 24, 32, 40, 48, 60, 72, 84, and 96. A physical exam, vital signs, sirolimus levels, as well as blood and urine collection will occur at all visits. A renal biopsy will be performed at week 96.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Sirolimus, Drug: MMF or AzathioprineParticipants who have been maintained on MMF at study entry will start the study on 600 mg/m2 MMF orally daily. Participants who have been maintained on Azathioprine due to MMF intolerance will receive 1 mg/kg Azathioprine orally daily. Participants will continue receiving sirolimus throughout the study. However, MMF or Azathioprine will be withdrawn gradually over a period of at least 6 months. Dosage will be reduced by 25% initially and by 25% every subsequent 2 months resulting in complete withdrawal by 6 months. |
Who may qualify
- Ages
- 1 year to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Participant and/or parent guardian able to understand and willing to provide informed consent
- Previously enrolled and completed the CCTPT-PC01 study and within the 36 months post-completion timeframe prior to study entry
- Currently receiving sirolimus and MMF or azathioprine therapy
- No history of acute rejection episodes
- No evidence of acute or chronic rejection on the 24 month CCTPT-PC01 protocol biopsy or any subsequent biopsy obtained after that time prior to study entry
Key exclusion criteria (7 listed)
- Total lymphocyte count less than 400 mm^3
- Acute or chronic infection at study entry
- Treatment with investigational drug within 1 month prior to study entry
- Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the study
- History of allergic reaction to Iodine GFR assay
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 |
|---|---|---|
| SirolimusAlso: Rapamycin, RapamuneOral tablets or liquid taken every 12 hours. Dosage adjusted to attain target trough levels of 8-12 ng/mL. Participants who have maintained such levels at study entry on once daily dosage will be permitted to continue on once daily dosing. | Drug | 1 |
| MMF or Azathioprine600 mg/m2 MMF taken orally daily or Azathioprine orally daily. Dosage of Azathioprine is dependent on weight. MMF or Azathioprine will be reduced by 25% initially and by 25% every 2 months resulting in complete withdrawal by 6 months. | Drug | 1 |
Primary outcome
Per-person incidence of acute rejection episodes and death or graft loss
Time frame: Throughout study
11 secondary outcomes
Incidence of chronic allograft dysfunction
Time frame: Throughout study
Incidence of sub-clinical rejection
Time frame: Throughout study
Incidence of hospitalizations
Time frame: Throughout study
Incidence of surgical complications
Time frame: Throughout study
Resumption of MMF or other therapy
Time frame: Throughout study
Incidence, severity, and treatment of anemia, hypertension, hyperlipidemia, proteinuria, thrombocytopenia, and leukopenia
Time frame: Throughout study
Incidence, severity, and treatment of opportunistic infections
Time frame: Throughout study
Incidence of biopsy proven PTLD
Time frame: Throughout study
Renal function assessed by measured GFR
Time frame: At baseline, week 48 and week 96
Development of donor-specific or non-specific anti-HLA antibodies
Time frame: Throughout study
Evolution of immune response in cellular, humoral, and molecular assays from baseline through week 96
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 15 Feb 2013.
- Background: PubMed 18416737McDonald RA, Smith JM, Ho M, Lindblad R, Ikle D, Grimm P, Wyatt R, Arar M, Liereman D, Bridges N, Harmon W; CCTPT Study Group. Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. Am J Transplant. 2008 May;8(5):984-9. doi: 10.1111/j.1600-6143.2008.02167.x.
- Background: PubMed 15888040Watson CJ, Bradley JA, Friend PJ, Firth J, Taylor CJ, Bradley JR, Smith KG, Thiru S, Jamieson NV, Hale G, Waldmann H, Calne R. Alemtuzumab (CAMPATH 1H) induction therapy in cadaveric kidney transplantation--efficacy and safety at five years. Am J Transplant. 2005 Jun;5(6):1347-53. doi: 10.1111/j.1600-6143.2005.00822.x.
- CTOTC WebsiteLink provided by the sponsor.
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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.
William H. Harmon, MD study chair
Boston Children's Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sirolimus and MMF or Azathioprine in people with Kidney Failure, Chronic and Kidney Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites 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 10 inclusion and 7 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 15 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Per-person incidence of acute rejection episodes and death or graft loss (time frame: Throughout study). 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 NCT00768729, which also lists 2 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 15 Feb 2013.