Tau/P-Tau and Neurocognitive Outcomes in Children

• ClinicalTrials.gov Identifier: NCT03511729
• Recruitment Status: Recruiting
• First Posted: April 30, 2018
• Last Update Posted: February 23, 2021
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Zhongcong Xie, Massachusetts General Hospital

Study Description

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.

Condition or disease
General Anesthetics Toxicity; Postoperative Cognitive Dysfunction; Child Development

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 Design

• Study Type: Observational
• Estimated Enrollment: 300 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Tau/P-Tau as Biomarkers of Anesthesia/Surgery-associated Neurocognitive Outcomes in Children
• Actual Study Start Date: June 1, 2018
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2023

Groups and Cohorts

Group/Cohort
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)

Outcome Measures

Primary Outcome Measures :

1. Blood Tau/P-Tau level before the surgery (baseline) [ Time Frame: 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
2. Blood Tau/P-Tau level at postoperative 3 hours [ Time Frame: At 3 hours after the surger ]
   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
3. Blood Tau/P-Tau level at postoperative 6 hours [ Time Frame: 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 :

1. Neurocognitive function before the surgery (baseline) [ Time Frame: Before the surgery ]
   Cognitive function will be assessed by using a battery of neurocognitive tests before the surgery
2. Neurocognitive function at postoperative one year [ Time Frame: At postoperative one year ]
   Cognitive function will be assessed by using a battery of neurocognitive tests at postoperative one year
3. Feces Tau/P-Tau level before the surgery (baseline) [ Time Frame: Before the surgery ]
   Feces will be collected to measure the level of Tau/P-Tau before the surgery
4. Feces Tau/P-Tau level at postoperative one day [ Time Frame: At postoperative one day ]
   Feces will be collected to measure the level of Tau/P-Tau at postoperative one day
5. Urine Tau/P-Tau level before the surgery (baseline) [ Time Frame: Before the surgery ]
   Urine will be collected to measure the level of Tau/P-Tau before the surgery
6. Urine Tau/P-Tau level at postoperative one day [ Time Frame: At postoperative one day ]
   Urine will be collected to measure the level of Tau/P-Tau at postoperative one day
7. Saliva Tau/P-Tau level before the surgery (baseline) [ Time Frame: Before the surgery ]
   Saliva will be collected to measure the level of Tau/P-Tau before the surgery
8. Saliva Tau/P-Tau level at postoperative one day [ Time Frame: At postoperative one day ]
   Saliva will be collected to measure the level of Tau/P-Tau at postoperative one day

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.

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 5 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

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.

Contacts and Locations

Contacts

Contact: Zhongcong Xie, MD, PhD; 6177249308; ZXIE@mgh.harvard.edu

Contact: Zhongcong Xie, MD,PhD; 6177249308; zhongcong_xie@hms.harvard.edu

Locations

United States, Massachusetts

Shriners Hospitals for Children; Recruiting

Boston, Massachusetts, United States, 02114

Contact: J.A. Jeevendra Martyn, M.D. 617-726-8807 JMARTYN@mgh.harvard.edu

Zhongcong Xie; Recruiting

Boston, Massachusetts, United States, 02129-2020

Contact: Zhongcong Xie, PhD, MD 617-724-9308 zxie@mgh.harvard.edu

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

• Principal Investigator: Zhongcong Xie, MD, PhD; Massachusetts General Hospital

More Information

Publications:

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.

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.

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.

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.

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.

• Responsible Party: Zhongcong Xie, Professor of Anesthesia, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03511729
• Other Study ID Numbers: MassGH-002
• First Posted: April 30, 2018
• Last Update Posted: February 23, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All individual participant data that underlie results in a publication will be available to other researchers.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (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.
• URL: https://clinicaltrials.gov/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Zhongcong Xie, Massachusetts General Hospital:

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

Additional relevant MeSH terms:

Postoperative Cognitive Complications; Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Postoperative Complications; Pathologic Processes