CNTRP POSITIVE Study

Summary

Adequate control of immunosuppression is critical in preventing graft failure after solid organ transplantation (SOT) and in avoiding life-threatening viral and malignant complications. Prolonging patient and graft survival and delaying re-transplantation as children reach adulthood is critical to optimal use of a scarce resource. This requires tailoring post-transplant management to the unique needs of the child. Immunosuppression management is challenging in infants, children and youth. The interval from birth to young adulthood sees profound changes in physiological processes, body size and immune maturation; infancy and adolescence are the periods of most rapid and dramatic change. Three pivotal factors affect immunosuppression control in the child: 1) age-dependent variation in drug metabolism; 2) developmental changes in immune function with increased childhood susceptibility to infections, including those caused by viruses; and 3) behavioural changes in adolescence and young adulthood linked with poor treatment adherence.

This project will identify the most important factors influencing immunosuppression control across the pediatric age range, from infancy to young adulthood, including age-related changes in drug metabolism, immune function, and susceptibility to viral infections, as well as health care system factors affecting treatment adherence. This is the first comprehensive, multi-organ transplant study to identify age-related biologic and health care systems determinants of variability in immunosuppression control in children and youth. Results will inform personalized age-appropriate strategies to improve immunosuppression control and reduce the unacceptably high graft failure and viral complication rates in this vulnerable population.

The POSITIVE Study brings together researchers across Canada and is one of 6 projects and 3 cores that constitute the Canadian Institute of Health Research (CIHR) funded interdisciplinary research program called the Canadian National Transplant Research Program (CNTRP). The CNTRP is a national program designed to increase organ and tissue donation in Canada and enhance the survival and quality of life of Canadians who receive transplants. As a national program, CNTRP provides robust power for pediatric studies that would not otherwise be possible. While primarily focused on issues unique to a pediatric and young adult population, this study will interact closely with all other CNTRP projects. These reciprocal interactions will accelerate new discovery that can be cross-applied in different populations outside of pre-specified age groups. Interactions will ensure rapid knowledge transfer, uptake and dissemination into practice. This is the largest national cohort study of pediatric transplant patients to date in Canada, and it will create a longitudinal dataset with clinical and biological specimens linkable to transplant registries and provincial administrative datasets.

Conditions

• Transplant
• Adaptive Immunity
• EBV
• Medication Adherence
• PTLD

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• Alberta Children's Hospital

  collaborator OTHER

• Stollery Children's Hospital

  collaborator OTHER

• St. Justine's Hospital

  collaborator OTHER

• The Children's Hospital of Winnipeg

  collaborator OTHER

• Montreal Children's Hospital of the MUHC

  collaborator OTHER

• Provincial Health Services Authority

  collaborator OTHER

• Toronto General Hospital

  collaborator OTHER

• Vancouver General Hospital

  collaborator OTHER

• Royal Victoria Hospital, Canada

  collaborator OTHER

• The Ottawa Hospital

  collaborator OTHER

• Foothills Medical Centre

  collaborator OTHER

• Centre hospitalier de l'Université de Montréal (CHUM)

  collaborator OTHER

• University of British Columbia

  collaborator OTHER

• The Hospital for Sick Children

  lead OTHER

Principal Investigators

• Seema Mital, MD · SickKids Hospital

Eligibility

Min Age

0 Years

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-04-30

Primary Completion

2019-11-30

Completion

2020-04-30

Countries

• Canada

Study Locations