NCT01993836

Brief Summary

This study will examine the hypothesis that changes in the cognition (i.e. thinking and memory) after anesthesia and surgery are correlated with changes in markers of Alzheimers Disease in the fluid around the brain and spinal cord (i.e. cerebrospinal fluid, or CSF), and/or changes in brain connectivity. The investigators will also examine whether different types of anesthesia have different effects on these CSF markers of Alzheimers disease, or different effects on thinking and memory after anesthesia and surgery, or differential effects on the correlation between cognitive changes and CSF marker changes.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
191

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Nov 2013

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2013

Completed
14 days until next milestone

First Submitted

Initial submission to the registry

November 15, 2013

Completed
10 days until next milestone

First Posted

Study publicly available on registry

November 25, 2013

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 10, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 10, 2019

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

May 5, 2020

Completed
Last Updated

March 22, 2023

Status Verified

March 1, 2023

Enrollment Period

5.2 years

First QC Date

November 15, 2013

Results QC Date

January 7, 2020

Last Update Submit

March 20, 2023

Conditions

Keywords

isofluranepropofoltotal intravenous anesthesiainhaled anestheticvolatile anestheticanesthesiadeliriumPost Operative Cognitive DysfunctionAlzheimer's DiseaseMild Cognitive Impairment

Outcome Measures

Primary Outcomes (2)

  • Correlation Between Perioperative Change in Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change

    Spearman correlation was used here as the CSF markers follow a skewed distribution. Spearman correlation describes the strength of the monotonic relationship between two measures and is bounded between -1 and 1. Negative values indicate an inverse relationship while positive values mean that the variables move in tandem.

    Baseline to 6 weeks

  • Correlation Between Perioperative Change in Ratios of Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change

    Spearman correlation was used here as the ratio of CSF markers follow a skewed distribution. Spearman correlation describes the strength of the monotonic relationship between two measures and is bounded between -1 and 1. Negative values indicate an inverse relationship while positive values mean that the variables move in tandem.

    Baseline to 6 weeks

Secondary Outcomes (4)

  • Continuous Cognitive Index Score Change Difference Between Anesthetic Agent Groups

    Baseline to 6 weeks

  • Change in CSF Markers of Alzheimers Disease by Anesthetic Agent Group

    Baseline to 6 weeks

  • Change in Ratio of CSF Markers of Alzheimers Disease by Anesthetic Agent Group

    baseline to 6-weeks

  • Perioperative CSF Tau/Abeta Ratio Change

    Baseline to 24 hours

Study Arms (2)

Total Intravenous Anesthesia with Propofol

ACTIVE COMPARATOR

Patients in this arm will receive general anesthesia with propofol as the primary amnestic agent.

Drug: Total intravenous anesthesia with propofol

General anesthesia with Isoflurane

ACTIVE COMPARATOR

Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent.

Drug: General anesthesia with isoflurane

Interventions

Total Intravenous Anesthesia with Propofol
General anesthesia with Isoflurane

Eligibility Criteria

Age60 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Surgical patients 60 years of age or older
  • Surgery scheduled to last at least 2 hours (including time for anesthesia induction, etc)
  • English speaking ability.
  • Ability to give informed consent

You may not qualify if:

  • Inmate of a correctional facility (i.e. prisoners).
  • Pregnancy
  • Documented or suspected family or personal history of malignant hyperthermia.
  • Patient unable to receive either propofol or isoflurane due to allergy or other specific contraindication.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (2)

  • Villalobos D, Reese M, Wright MC, Wong M, Syed A, Park J, Hall A, Browndyke JN, Martucci KT, Devinney MJ, Acker L, Moretti EW, Talbot L, Colin B, Ohlendorf B, Waligorska T, Shaw LM, Whitson HE, Cohen HJ, Mathew JP, Berger M. Perioperative changes in neurocognitive and Alzheimer's disease-related cerebrospinal fluid biomarkers in older patients randomised to isoflurane or propofol for anaesthetic maintenance. Br J Anaesth. 2023 Aug;131(2):328-337. doi: 10.1016/j.bja.2023.04.019. Epub 2023 Jun 2.

  • Berger M, Browndyke JN, Cooter Wright M, Nobuhara C, Reese M, Acker L, Bullock WM, Colin BJ, Devinney MJ, Moretti EW, Moul JW, Ohlendorf B, Laskowitz DT, Waligorska T, Shaw LM, Whitson HE, Cohen HJ, Mathew JP; MADCO-PC Investigators. Postoperative changes in cognition and cerebrospinal fluid neurodegenerative disease biomarkers. Ann Clin Transl Neurol. 2022 Feb;9(2):155-170. doi: 10.1002/acn3.51499. Epub 2022 Feb 1.

MeSH Terms

Conditions

Alzheimer DiseaseEmergence DeliriumDeliriumCognitive Dysfunction

Interventions

PropofolAnesthesia, GeneralIsoflurane

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental DisordersConfusionNeurobehavioral ManifestationsNeurologic ManifestationsPostoperative ComplicationsPathologic ProcessesPathological Conditions, Signs and SymptomsSigns and SymptomsCognition Disorders

Intervention Hierarchy (Ancestors)

PhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsAnesthesiaAnesthesia and AnalgesiaMethyl EthersEthers

Results Point of Contact

Title
Miles Berger, MD, PhD
Organization
Duke University

Study Officials

  • Miles Berger, MD, PhD

    Duke University Medical Center, Anesthesiology Department, Neuroanesthesia Division

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 15, 2013

First Posted

November 25, 2013

Study Start

November 1, 2013

Primary Completion

January 10, 2019

Study Completion

January 10, 2019

Last Updated

March 22, 2023

Results First Posted

May 5, 2020

Record last verified: 2023-03

Locations