General Anesthetics ToxicityNCT03511729
Tau/P-Tau and Neurocognitive Outcomes in Children
An observational study of General Anesthetics Toxicity and Postoperative Cognitive Dysfunction, run by Massachusetts General Hospital at 2 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 3 to 5 years
- Conditions the study is for
- General Anesthetics Toxicity, Postoperative Cognitive Dysfunction, Child Development
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jun 2018to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 5 years
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- between age 3 and 5 at the time of the first neurocognitive test;
- scheduled for surgery under general anesthesia
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Boston Childrens Hospital
Boston, Massachusetts, 02115
Zhongcong Xie
Boston, Massachusetts, 02129-2020
About this study
Official title: Tau/P-Tau as Biomarkers of Anesthesia/Surgery-associated Neurocognitive Outcomes in Children
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.
Read the detailed description
This proposed studies have two specific aims:
- 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.
- 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.
- Keywords
- Tau/P-Tau, biomarker, neurocognitive, outcomes, children
- Medical subject headings
- Postoperative Cognitive Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: At 6 hours after the surgery
Secondary outcomes (8)
Neurocognitive function before the surgery (baseline)
Cognitive function will be assessed by using a battery of neurocognitive tests before the surgery
Measured: Before the surgery
Neurocognitive function at postoperative one year
Cognitive function will be assessed by using a battery of neurocognitive tests at postoperative one year
Measured: At postoperative one year
Feces Tau/P-Tau level before the surgery (baseline)
Feces will be collected to measure the level of Tau/P-Tau before the surgery
Measured: Before the surgery
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
Measured: At postoperative one day
Urine Tau/P-Tau level before the surgery (baseline)
Urine will be collected to measure the level of Tau/P-Tau before the surgery
Measured: Before the surgery
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
Measured: At postoperative one day
Saliva Tau/P-Tau level before the surgery (baseline)
Saliva will be collected to measure the level of Tau/P-Tau before the surgery
Measured: Before the surgery
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
Measured: At postoperative one day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2018
- Study start1 Jun 2018
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for General Anesthetics ToxicityStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Zhongcong Xie, Massachusetts General Hospital
- Investigators
- Zhongcong Xie, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03511729
- Sponsor's protocol ID
- 2019P000757
- Other IDs
- 5R21HD098754-02
- Status last verified
- Apr 2022
- First submitted
- 11 Apr 2018
- Last updated
- 25 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data that underlie results in a publication will be available to other researchers.
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.
PubMed 19293700Flick 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.
PubMed 21969289Kalkman 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.
PubMed 19293699Sun 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.
PubMed 21148656Ing 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.
PubMed 25144506
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tau/P-Tau as Biomarkers of Anesthesia/Surgery-associated Neurocognitive Outcomes in Children
- ClinicalTrials.gov ID
- NCT03511729
- Acronym / sponsor ID
- 2019P000757
- Keywords
- Tau/P-Tau, biomarker, neurocognitive, outcomes, children
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 1 Jun 2018 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 30 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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) |
Who may qualify
- Ages
- 3 to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (2 listed)
- between age 3 and 5 at the time of the first neurocognitive test;
- scheduled for surgery under general anesthesia
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
Blood Tau/P-Tau level at postoperative 3 hours
Time frame: 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
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
8 secondary outcomes
Neurocognitive function before the surgery (baseline)
Time frame: Before the surgery
Neurocognitive function at postoperative one year
Time frame: At postoperative one year
Feces Tau/P-Tau level before the surgery (baseline)
Time frame: Before the surgery
Feces Tau/P-Tau level at postoperative one day
Time frame: At postoperative one day
Urine Tau/P-Tau level before the surgery (baseline)
Time frame: Before the surgery
Urine Tau/P-Tau level at postoperative one day
Time frame: At postoperative one day
Saliva Tau/P-Tau level before the surgery (baseline)
Time frame: Before the surgery
Saliva Tau/P-Tau level at postoperative one day
Time frame: At postoperative one day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2022.
- Background: PubMed 19293700Wilder 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.
- Background: PubMed 21969289Flick 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.
- Background: PubMed 19293699Kalkman 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.
- Background: PubMed 21148656Sun 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.
- Background: PubMed 25144506Ing 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.
- Individual participant dataSharing planned: Yes. All individual participant data that underlie results in a publication will be available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhongcong Xie, MD, PhD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of General Anesthetics Toxicity and Postoperative Cognitive Dysfunction, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood Tau/P-Tau level before the surgery (baseline) (time frame: Before the surgery). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03511729, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2022.