Tau/P-Tau and Neurocognitive Outcomes in Children

NCT03511729 | Unknown

• 2 other identifiers: 2019P0007575R21HD098754-02
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 2

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.

Conditions

General Anesthetics Toxicity; Postoperative Cognitive Dysfunction; Child Development

Keywords

Tau/P-Tau; biomarker; neurocognitive; outcomes; children

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (8)

• Neurocognitive function before the surgery (baseline)

  Before the surgery

• Neurocognitive function at postoperative one year

  At postoperative one year

• Feces Tau/P-Tau level before the surgery (baseline)

  Before the surgery

• Feces Tau/P-Tau level at postoperative one day

  At postoperative one day

• Urine Tau/P-Tau level before the surgery (baseline)

  Before the surgery

Study Arms (2)

A single exposure to general anesthesia

Participants who have surgery under general anesthesia (without anesthesia/surgery before)

Multiple exposures to general anesthesia

Participants who have surgery under general anesthesia (had anesthesia/surgery before)

Eligibility Criteria

• Age: 3 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

Boston Childrens Hospital

Boston, Massachusetts, 02115, United States

Location

Zhongcong Xie

Boston, Massachusetts, 02129-2020, United States

Location

Related Publications (5)

• 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.

  PMID: 19293700 BACKGROUND

• 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.

  PMID: 21969289 BACKGROUND

• 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.

  PMID: 19293699 BACKGROUND

• 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.

  PMID: 21148656 BACKGROUND

• 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.

  PMID: 25144506 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

The investigators will harvest 300ul blood of participants before and 3, 6 hours after the surgery. Urine, feces and saliva from these participants will also be harvested.

MeSH Terms

Conditions

Postoperative Cognitive Complications

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Zhongcong Xie, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesia

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: April 30, 2018
• Study Start: June 1, 2018
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Individual participant data will be available 6 months after publication
• Access Criteria: Principle investigator will review the requests and determine what information should be shared.

Locations

US (2)