Tau/P-Tau and Neurocognitive Outcomes in Children

• Conditions: General Anesthetics Toxicity; Postoperative Cognitive Dysfunction; Child Development

• Registration Number: NCT03511729
• Lead Sponsor: Massachusetts General 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.

Study Timeline

• Study First Submitted: 2018-04-11
• Study First Submitted QC: 2018-04-18
• Study First Posted: 2018-04-30
• Study Start: 2018-06-01
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-15
• Last Update Posted: 2022-04-25
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Blood Tau/P-Tau level before the surgery (baseline)	Before the surgery	300 ul venous blood before the surgery will be collected from the inserted intravenous catheter to measure the levels of Tau/P-Tau
Blood Tau/P-Tau level at postoperative 3 hours	At 3 hours after the surgery	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
Blood Tau/P-Tau level at postoperative 6 hours	At 6 hours after the surgery	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

Secondary Outcome Measures

Name	Time	Method
Neurocognitive function before the surgery (baseline)	Before the surgery	Cognitive function will be assessed by using a battery of neurocognitive tests before the surgery
Saliva Tau/P-Tau level before the surgery (baseline)	Before the surgery	Saliva will be collected to measure the level of Tau/P-Tau before the surgery
Feces Tau/P-Tau level before the surgery (baseline)	Before the surgery	Feces will be collected to measure the level of Tau/P-Tau before the surgery
Urine Tau/P-Tau level before the surgery (baseline)	Before the surgery	Urine will be collected to measure the level of Tau/P-Tau before the surgery
Neurocognitive function at postoperative one year	At postoperative one year	Cognitive function will be assessed by using a battery of neurocognitive tests at postoperative one year
Feces Tau/P-Tau level at postoperative one day	At postoperative one day	Feces will be collected to measure the level of Tau/P-Tau at postoperative one day
Urine Tau/P-Tau level at postoperative one day	At postoperative one day	Urine will be collected to measure the level of Tau/P-Tau at postoperative one day
Saliva Tau/P-Tau level at postoperative one day	At postoperative one day	Saliva will be collected to measure the level of Tau/P-Tau at postoperative one day

Trial Locations

Locations (2)

Zhongcong Xie; 🇺🇸 Boston, Massachusetts, United States

Boston Childrens Hospital; 🇺🇸 Boston, Massachusetts, United States