Tau/P-Tau and Neurocognitive Outcomes in Children

Child Development Clinical Trial

Official title:

Tau/P-Tau as Biomarkers of Anesthesia/Surgery-associated Neurocognitive Outcomes in Children

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03511729
• Other study ID #: 2019P000757
• Secondary ID: 5R21HD098754-02
• Status: Active, not recruiting
• Start date: June 1, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: April 2022
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 5 Years

Eligibility

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.

Related Conditions & MeSH terms

• Child Development
• Cognitive Dysfunction
• General Anesthetics Toxicity
• Postoperative Cognitive Complications
• Postoperative Cognitive Dysfunction

Locations

Country	Name	City	State
United States	Boston Childrens Hospital	Boston	Massachusetts
United States	Zhongcong Xie	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. Erratum in: Pediatrics. 2012 Mar;129(3):595. — View 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. — View 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. — View Citation

Sun L. Early childhood general anaesthesia exposure and neurocognitive development. Br J Anaesth. 2010 Dec;105 Suppl 1:i61-8. doi: 10.1093/bja/aeq302. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood Tau/P-Tau level before the surgery (baseline)	300 ul venous blood before the surgery will be collected from the inserted intravenous catheter to measure the levels of Tau/P-Tau	Before the surgery
Primary	Blood Tau/P-Tau level at postoperative 3 hours	300 ul venous blood at 3 hours after the surgery will be collected from the inserted intravenous catheter to measure the levels of Tau/P-Tau	At 3 hours after the surgery
Primary	Blood Tau/P-Tau level at postoperative 6 hours	300 ul venous blood at 6 hours after the surgery will be collected from the inserted intravenous catheter to measure the levels of Tau/P-Tau	At 6 hours after the surgery
Secondary	Neurocognitive function before the surgery (baseline)	Cognitive function will be assessed by using a battery of neurocognitive tests before the surgery	Before the surgery
Secondary	Neurocognitive function at postoperative one year	Cognitive function will be assessed by using a battery of neurocognitive tests at postoperative one year	At postoperative one year
Secondary	Feces Tau/P-Tau level before the surgery (baseline)	Feces will be collected to measure the level of Tau/P-Tau before the surgery	Before the surgery
Secondary	Feces Tau/P-Tau level at postoperative one day	Feces will be collected to measure the level of Tau/P-Tau at postoperative one day	At postoperative one day
Secondary	Urine Tau/P-Tau level before the surgery (baseline)	Urine will be collected to measure the level of Tau/P-Tau before the surgery	Before the surgery
Secondary	Urine Tau/P-Tau level at postoperative one day	Urine will be collected to measure the level of Tau/P-Tau at postoperative one day	At postoperative one day
Secondary	Saliva Tau/P-Tau level before the surgery (baseline)	Saliva will be collected to measure the level of Tau/P-Tau before the surgery	Before the surgery
Secondary	Saliva Tau/P-Tau level at postoperative one day	Saliva will be collected to measure the level of Tau/P-Tau at postoperative one day	At postoperative one day