Brief Summary
CMV infection and disease remain a significant clinical challenge for pediatric solid organ transplant (SOT) recipients. Current prevention strategies are limited to prophylaxis in which antiviral medication is administered for a period of several months or preemption in which close monitoring of CMV viral load from the peripheral blood is performed and treatment is initiated when CMV is detected. Each of these strategies has risks, costs, and limitations associated with it. Recently, assays for measurement of an individual patient's CMV immunity have been developed and are clinically available. One of these is the Viracor CMV T cell Immunity Panel. This flow cytometry based assay is performed on peripheral blood and measures cytokine release in response to CMV antigen stimulation by flow cytometry. The thresholds for this assay that confer protection against CMV infection in pediatric SOT recipients are not known. Defining CMV-specific cell mediated immune response thresholds that confer protection against CMV reactivation could inform patient specific durations of antiviral prophylaxis or pre-emptive surveillance testing. Therefore, the objective of this study is to quantify CMVresponsive T lymphocyte populations by flow cytometry (Viracor CMV T cell Immunity Panel) in pediatric heart, kidney, and liver transplant recipients within the first year of transplantation and to investigate potential threshold values that correlate with protection against CMV infection (DNAemia).
Brief Title
CMV T Cell Immunity in Pediatric Solid Organ Transplant Recipients
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Heart Transplant Infection
Kidney Transplant Infection
Liver Transplant Infection
CMV
Eligibility Criteria
Inclusion Criteria:
1. \< 18 years of age at the time of pre-transplant enrollment
2. Potential subject is undergoing evaluation or is currently listed for isolated heart, kidney, or liver transplantation at a participating transplant center OR is anticipated to undergo living-donor kidney or liver transplantation
3. Anticipated to receive ≤ 200 days of antiviral chemoprophylaxis
Note: Subjects who are consented, enrolled, and undergo transplantation at \<18 years of age will remain in the study and be followed post-transplant according to the study plan after they turn 18 years of age. Subjects will be re-consented to remain in the study at their first study visit after turning 18 years of age.
Exclusion Criteria:
I. Exclusion Criteria pre-transplant
1. Prior history of any organ transplant
2. Prior history of hematopoietic cell transplant
3. Anticipated to receive more than one organ at the time of transplant
4. Anticipated to receive \> 200 days of CMV antiviral chemoprophylaxis as part of the local transplant center's standard CMV prevention protocol
5. History of underlying primary (genetic) T cell immune deficiency
II. Exclusion Criteria post-enrollment A) Removal from study due to minimal risk for CMV infection
1. CMV seronegative children \>= 12 months of age will be enrolled pre-transplant but will subsequently be excluded from the study IF they receive an organ from a CMV seronegative donor (CMV D-/R-).
2. Infants \<12 months will be considered seronegative regardless of their CMV IgG status (whether or not this testing was obtained by the local transplant center) UNLESS the infant has a positive pre-transplant CMV culture (from urine) or a positive pre-transplant CMV PCR (from urine, saliva, or blood). Infants \<12 months of age without evidence of prior CMV infection (as defined by these preceding criteria) will be excluded from post-transplant follow up IF they receive an organ from a CMV seronegative donor due to low risk for post-transplant CMV infection. Infants \<12 months of age with evidence of prior CMV infection (as defined above) will remain in the study following transplantation.
B) Removal from study due to age
a. Subjects who are enrolled at \<18 years of age but are not transplanted prior to their 18th birthday will be removed from the study and will not have further pre- or post-transplant follow up.
1. \< 18 years of age at the time of pre-transplant enrollment
2. Potential subject is undergoing evaluation or is currently listed for isolated heart, kidney, or liver transplantation at a participating transplant center OR is anticipated to undergo living-donor kidney or liver transplantation
3. Anticipated to receive ≤ 200 days of antiviral chemoprophylaxis
Note: Subjects who are consented, enrolled, and undergo transplantation at \<18 years of age will remain in the study and be followed post-transplant according to the study plan after they turn 18 years of age. Subjects will be re-consented to remain in the study at their first study visit after turning 18 years of age.
Exclusion Criteria:
I. Exclusion Criteria pre-transplant
1. Prior history of any organ transplant
2. Prior history of hematopoietic cell transplant
3. Anticipated to receive more than one organ at the time of transplant
4. Anticipated to receive \> 200 days of CMV antiviral chemoprophylaxis as part of the local transplant center's standard CMV prevention protocol
5. History of underlying primary (genetic) T cell immune deficiency
II. Exclusion Criteria post-enrollment A) Removal from study due to minimal risk for CMV infection
1. CMV seronegative children \>= 12 months of age will be enrolled pre-transplant but will subsequently be excluded from the study IF they receive an organ from a CMV seronegative donor (CMV D-/R-).
2. Infants \<12 months will be considered seronegative regardless of their CMV IgG status (whether or not this testing was obtained by the local transplant center) UNLESS the infant has a positive pre-transplant CMV culture (from urine) or a positive pre-transplant CMV PCR (from urine, saliva, or blood). Infants \<12 months of age without evidence of prior CMV infection (as defined by these preceding criteria) will be excluded from post-transplant follow up IF they receive an organ from a CMV seronegative donor due to low risk for post-transplant CMV infection. Infants \<12 months of age with evidence of prior CMV infection (as defined above) will remain in the study following transplantation.
B) Removal from study due to age
a. Subjects who are enrolled at \<18 years of age but are not transplanted prior to their 18th birthday will be removed from the study and will not have further pre- or post-transplant follow up.
Inclusion Criteria
Inclusion Criteria:
1. \< 18 years of age at the time of pre-transplant enrollment
2. Potential subject is undergoing evaluation or is currently listed for isolated heart, kidney, or liver transplantation at a participating transplant center OR is anticipated to undergo living-donor kidney or liver transplantation
3. Anticipated to receive ≤ 200 days of antiviral chemoprophylaxis
Note: Subjects who are consented, enrolled, and undergo transplantation at \<18 years of age will remain in the study and be followed post-transplant according to the study plan after they turn 18 years of age. Subjects will be re-consented to remain in the study at their first study visit after turning 18 years of age.
1. \< 18 years of age at the time of pre-transplant enrollment
2. Potential subject is undergoing evaluation or is currently listed for isolated heart, kidney, or liver transplantation at a participating transplant center OR is anticipated to undergo living-donor kidney or liver transplantation
3. Anticipated to receive ≤ 200 days of antiviral chemoprophylaxis
Note: Subjects who are consented, enrolled, and undergo transplantation at \<18 years of age will remain in the study and be followed post-transplant according to the study plan after they turn 18 years of age. Subjects will be re-consented to remain in the study at their first study visit after turning 18 years of age.
Gender
All
Gender Based
false
Keywords
cmv
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
0 Years
NCT Id
NCT03924219
Org Class
Other
Org Full Name
Vanderbilt University Medical Center
Org Study Id
180947
Overall Status
Active, not recruiting
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Assessment of CMV-specific T Cell Responses by Flow Cytometry With Intracellular Cytokine Staining to Predict CMV Infection Risk in Pediatric Solid Organ Transplant Recipients
Primary Outcomes
Outcome Description
CMV Infection as measured by CMV DNAemia or CMV disease
Outcome Measure
CMV Infection Incidence
Outcome Time Frame
12 months post-transplantation
Secondary Outcomes
Outcome Description
Viracor T cell Immunity Assay
Outcome Time Frame
12 months post-transplantation
Outcome Measure
Frequency of detectable CMV T cell Immunity
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Study Population
Pediatric patients \<18 years of age listed or anticipated to undergo kidney, heart, or liver transplantation.
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Betsy Herold
Investigator Email
betsy.herold@einsteinmed.org
Investigator Phone
718-839-7460