Immune Development in Pediatric Transplantation (IMPACT)

End Stage Renal Disease Clinical Trial

Official title:

Immune Development and Alloimmunity in Pediatric Renal Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00951353
• Other study ID #: DAIT CTOTC-02
• Status: Completed
• Start date: July 2009
• Est. completion date: March 2013

Study information

• Verified date: December 2018
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Transplantation is the preferred method of treatment for end-stage renal disease (ESRD) in children. Over the past forty years, the use of newer immunosuppressive drugs has decreased the risk for organ rejection considerably, and improved short-term outcomes. However, these costly and complicated life-long treatment regimens also cause serious side effects. This has been particularly true for children, who undergo treatment with these drugs at the same time they are transitioning, physically and emotionally, from childhood to adulthood. These factors lead to significantly reduced life-spans, decreased drug regimen adherence, and an increased need for re-transplantation, as compared with adults.

Current immunosuppressive procedures and strategies for children mimic those for adults, despite the difference between the two populations' immune systems and needs. New strategies aimed at tailoring to an individual child's needs would both reduce the risk of complications and improve outcomes. The purpose of this study is to generate information which will help to change the current practice of pediatric transplantation into one that is more individualized and preventative.

Description:

Over the past forty years, the use of increasingly effective immunosuppressive drugs has decreased the risk for organ rejection (acute rejection, AR) considerably, and improved short-term outcomes. However, these costly and complicated life-long treatment regimens also cause serious complications in the long-term.

While transplant recipients live significantly longer lives than patients on dialysis, transplant recipients still have much shorter life spans than their healthy counterparts. Among reasons for this difference in life-expectancy are the immunosuppressive-drug related side effects that can lead to complications such as life threatening infections, malignancies, high blood pressure, heart disease, and diabetes. Additionally, certain drugs used to prevent organ rejection are known to contribute to renal damage, leading many patients to experience graft loss within 15 years. To that end, many children undergoing successful kidney transplantation require re-transplantation as adults. Therefore, while transplantation yields high success rates in the short-term, the drugs that are responsible for this early and temporary success are also the cause of later, serious complications. This is especially true for children, who endure extended drug exposures.

The purpose of this study is to explore the impact of viral exposure on children who receive immunosuppressive medications after renal transplantation; study the cellular changes associated with these influences; monitor medication adherence; and observe how all these factors affect the outcome of kidney transplantation in children. The hope is to better understand these processes to optimize future transplant therapies for the pediatric transplant recipient.

This study is designed to observe the immune system response during the first year after kidney transplant. Cells of the immune system in the recipient's blood, urine, and transplanted kidney will be tested to observe how the drugs used to prevent rejection influence them, if these cells change over time, and if they are related to kidney rejection. The comparisons will allow researchers to study how the developing immune system interacts with the kidney transplant. Blood from the kidney donor will be requested so that researchers can study how the recipient's immune system interacts with donor cells.

This study will also look closely at how well participants take prescribed medications. Since transplant medications are known to change the immune system, tests of the immune system cells will be compared to tests designed to measure how accurately medications are taken. Medication adherence will be measured using electronic medication bottle cap records, paper survey results, and drug levels in the blood. In this way, the study team hopes to learn about the impact of children's medications on their immune system.

This study will take place at multiple transplant centers in the United States. It is observational and will involve approximately 75 pediatric renal participants. The study will last for a total of 3 years, which includes a 2 year accrual period and 12 month follow up. Clinical treatment will be determined by standard of care at each participating center. There will be Baseline assessments which will occur before and on the day of transplantation and follow-up study visits will take place at months 1, 3, 6, 9, and 12 after transplant. Study assessments and specimens will also be collected at the time of each clinically indicated biopsy. Study assessments during these follow-up visits will include vital signs; review of current medications; questions related to adverse events (infection, rejection, graft failure, malignancy); treatment adherence surveys; and specimen collection for local and central laboratory testing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: March 2013
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 20 Years

Eligibility

Inclusion Criteria:

• Parent or legal guardian willing to provide informed consent, if necessary

• 1 to 20 years of age (before 21st birthday) at the time of enrollment

• Undergoing renal transplantation

Exclusion Criteria:

• Need for multi-organ transplantation

• Any prior history of organ transplantation

• Inability or unwillingness of participant of their legal guardian to give written informed consent or comply with study protocol

Related Conditions & MeSH terms

• Chronic Kidney Failure
• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency

Locations

Country	Name	City	State
United States	Emory University/ Children's Healthcare of Atlanta	Atlanta	Georgia
United States	University of California at Los Angeles/ Mattel Children's Hospital	Los Angeles	California
United States	Stanford University Medical Center/ Lucille Packard Children's Hospital	Palo Alto	California

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Ettenger R, Chin H, Kesler K, Bridges N, Grimm P, Reed EF, Sarwal M, Sibley R, Tsai E, Warshaw B, Kirk AD. Relationship Among Viremia/Viral Infection, Alloimmunity, and Nutritional Parameters in the First Year After Pediatric Kidney Transplantation. Am J — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of biopsy proven and treated (steroid pulse, taper, immunosuppressant medication changes) acute rejection Banff grade borderline or higher		6 months after transplant
Secondary	Incidence of treated, clinically suspected rejection without biopsy		Throughout study
Secondary	Incidence of biopsy proven and clinically relevant chronic allograft nephropathy		Throughout study
Secondary	Incidence of infection and malignancy		Throughout study
Secondary	Incidence of medication non-adherence in pediatric kidney transplant recipients using self report questionnaires and electronic monitoring bottle caps		Throughout study
Secondary	Clinical impact of medication non-adherence with regard to the incidence of acute and chronic rejection		Throughout study
Secondary	The degree to which a child's T Cells are predominately naïve, TEM, TCM, or TTM as measured by MFC		Throughout study
Secondary	The heterologous alloreactivity of defined viral T cells for donor and third party alloantigens using MHC tetramers with specificity for CMV and EBV		Throughout study
Secondary	The peripheral blood, urine, and allograft transcriptional phenotypes specific to the MFC-defined T cell phenotype		Throughout study
Secondary	Formation of anti-donor HLA, non HLA, and MICA antibodies after transplantation as measured using Luminex platforms and microarray		Throughout study
Secondary	Identification of specific proteins in blood and allograft as correlated with rejection		Throughout study
Secondary	Barriers to adherence as indicated by AMBS, PMBS, and BMQ questionnaires		Throughout study
Secondary	Candidate surrogate markers of immunosuppressive medication non-adherence: • Tacrolimus drug level variation • De novo immune activation using real time PCR message for perforin and granzyme B, and • Anti-HLA antibodies		Throughout study

External Links

•   Clinical Trials in Organ Transplantation in Children (CTOT-C) program website
•   National Institute of Allergy and Infectious Diseases (NIAID) website