Clinical trial NCT03511729: Tau/P-Tau and Neurocognitive Outcomes in Children
Official title: Tau/P-Tau as Biomarkers of Anesthesia/Surgery-associated Neurocognitive Outcomes in Children
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: General Anesthetics Toxicity
Postoperative Cognitive Dysfunction
Child Development
Keywords: Tau/P-Tau
biomarker
neurocognitive
outcomes
children
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2018-04-30
Enrollment: 20
Sex: ALL
Minimum age (years): 3
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The investigators will enroll participants between age 3 and 5 years old who are scheduled for the surgery under general anesthesia from Shriners Hospital for Children or Boston Children Hospital.

Brief summary: The proposed studies are aimed to measure Tau and P-Tau levels in pre- and postoperative blood, urine, feces and saliva, as well as to assess pre- and postoperative neurocognitive function in children (3 to 5 years old) who will have surgery under general anesthesia (single versus multiple exposures). The studies will establish a system to study biomarkers of the anesthesia/surgery-associated neurocognitive impairment in children and generate hypothesis that Tau or P-Tau serves as the biomarker of such neurocognitive impairment in children.

Detailed description: This proposed studies have two specific aims:

1. To investigate the relationship between pre-operative or postoperative blood levels of Tau or P-Tau and neurocognitive outcomes. The working hypothesis is that pre- and postoperative blood Tau/P-Tau levels are higher in participants who develop neurocognitive impairment than those in the participants who do not develop it. The investigators will perform neurocognitive test before the surgery and then at 12 months after the surgery. The investigators will collect pre-operative and postoperative blood and measure Tau/P-Tau levels in the blood. Finally, the association of the changes in the Tau/P-Tau levels and neurocognitive scores will be assessed. More importantly, this Aim will establish an eligible: recruit ratio, retention rates, safety of the protocol, and power calculation, which will provide crucial information to guide better design of future R01 study.
2. To perform the feasibility studies of measuring Tau or P-Tau in urine, feces and saliva of the participants. The working hypothesis is that Tau/P-Tau in urine, feces or saliva of children can be measured. The investigators will use the nanobeam to measure Tau/P-Tau levels before and after the surgery. The investigators will then determine whether urine, feces and saliva can be used for the future studies to develop Tau/P-Tau as the biomarker of anesthesia/surgery-associated neurocognitive impairment in children.

Eligibility criteria: Inclusion Criteria:

1. between age 3 and 5 at the time of the first neurocognitive test;
2. scheduled for surgery under general anesthesia

Exclusion Criteria:

1. gestational age less than 36 weeks;
2. congenital heart disease that has required surgery or will require surgery or that requires ongoing pharmacotherapy;
3. known chromosomal abnormality or any other known acquired or congenital abnormalities which are likely to affect neurodevelopment;
4. known neurological injury such as cystic periventricular leukomalacia or grade 3 or 4 intra-ventricular hemorrhage (+/- post hemorrhage ventricular dilatation);
5. children for whom follow-up would be difficult for geographic or psychosocial reasons;
6. non-native English speaker (both child and parents);
7. severe visual or auditory disorder.

Primary outcomes:
measure: Blood Tau/P-Tau level before the surgery (baseline)
timeFrame: Before the surgery
measure: Blood Tau/P-Tau level at postoperative 3 hours
timeFrame: At 3 hours after the surgery
measure: Blood Tau/P-Tau level at postoperative 6 hours
timeFrame: At 6 hours after the surgery
Secondary outcomes:
measure: Neurocognitive function before the surgery (baseline)
timeFrame: Before the surgery
measure: Neurocognitive function at postoperative one year
timeFrame: At postoperative one year
measure: Feces Tau/P-Tau level before the surgery (baseline)
timeFrame: Before the surgery
measure: Feces Tau/P-Tau level at postoperative one day
timeFrame: At postoperative one day
measure: Urine Tau/P-Tau level before the surgery (baseline)
timeFrame: Before the surgery
measure: Urine Tau/P-Tau level at postoperative one day
timeFrame: At postoperative one day
measure: Saliva Tau/P-Tau level before the surgery (baseline)
timeFrame: Before the surgery
measure: Saliva Tau/P-Tau level at postoperative one day
timeFrame: At postoperative one day
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Childrens Hospital
state: Massachusetts
city: Boston
country: United States
facility: Zhongcong Xie
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Zhongcong Xie, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wilder RT, Flick RP, Sprung J, Katusic SK, Barbaresi WJ, Mickelson C, Gleich SJ, Schroeder DR, Weaver AL, Warner DO. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology. 2009 Apr;110(4):796-804. doi: 10.1097/01.anes.0000344728.34332.5d.
citation: Flick RP, Katusic SK, Colligan RC, Wilder RT, Voigt RG, Olson MD, Sprung J, Weaver AL, Schroeder DR, Warner DO. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics. 2011 Nov;128(5):e1053-61. doi: 10.1542/peds.2011-0351. Epub 2011 Oct 3.
citation: Kalkman CJ, Peelen L, Moons KG, Veenhuizen M, Bruens M, Sinnema G, de Jong TP. Behavior and development in children and age at the time of first anesthetic exposure. Anesthesiology. 2009 Apr;110(4):805-12. doi: 10.1097/ALN.0b013e31819c7124.
citation: Sun L. Early childhood general anaesthesia exposure and neurocognitive development. Br J Anaesth. 2010 Dec;105 Suppl 1(Suppl 1):i61-8. doi: 10.1093/bja/aeq302.
citation: Ing CH, DiMaggio CJ, Whitehouse AJ, Hegarty MK, Sun M, von Ungern-Sternberg BS, Davidson AJ, Wall MM, Li G, Sun LS. Neurodevelopmental outcomes after initial childhood anesthetic exposure between ages 3 and 10 years. J Neurosurg Anesthesiol. 2014 Oct;26(4):377-86. doi: 10.1097/ANA.0000000000000121.