Back to resultsMarkers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care (MADCO-PC)
Primary Purpose
Alzheimers Disease, Postoperative Delirium, Post Operative Cognitive Dysfunction
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Total intravenous anesthesia with propofol
General anesthesia with isoflurane
Sponsored by
About this trial
This is an interventional diagnostic trial for Alzheimers Disease focused on measuring isoflurane, propofol, total intravenous anesthesia, inhaled anesthetic, volatile anesthetic, anesthesia, delirium, Post Operative Cognitive Dysfunction, Alzheimer's Disease, Mild Cognitive Impairment
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- Duke University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Total Intravenous Anesthesia with Propofol
General anesthesia with Isoflurane
Arm Description
Patients in this arm will receive general anesthesia with propofol as the primary amnestic agent.
Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Continuous Cognitive Index Score Change Difference Between Anesthetic Agent Groups
To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the 10 cognitive test scores from baseline. To quantify overall cognitive function, a baseline cognitive index was first calculated as the mean of the preoperative domain scores. The cognitive index score has a mean of zero, thus any positive score is above the mean, any negative score is below the mean. A continuous change score was then calculated by subtracting the baseline from the 6-week cognitive index. A negative change score indicating decline and a positive score indicating improvement. The resulting outcome measure is unbounded with a standard deviation of 0.31 in the full surgical cohort.
Change in CSF Markers of Alzheimers Disease by Anesthetic Agent Group
CSF Markers of Alzheimer's Disease over time in the subjects treated with propofol versus those treated with isoflurane.
Change in Ratio of CSF Markers of Alzheimers Disease by Anesthetic Agent Group
Change in ratio of CSF Markers of Alzheimer's Disease over time in the subjects treated with propofol versus those treated with isoflurane.
Perioperative CSF Tau/Abeta Ratio Change
The perioperative change in the CSF tau/Abeta ratio from the start of anesthesia/surgery to 24 hours later.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01993836
Brief Title
Markers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care
Acronym
MADCO-PC
Official Title
Markers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
November 2013 (Actual)
Primary Completion Date
January 10, 2019 (Actual)
Study Completion Date
January 10, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimers Disease, Postoperative Delirium, Post Operative Cognitive Dysfunction
Keywords
isoflurane, propofol, total intravenous anesthesia, inhaled anesthetic, volatile anesthetic, anesthesia, delirium, Post Operative Cognitive Dysfunction, Alzheimer's Disease, Mild Cognitive Impairment
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
191 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Total Intravenous Anesthesia with Propofol
Arm Type
Active Comparator
Arm Description
Patients in this arm will receive general anesthesia with propofol as the primary amnestic agent.
Arm Title
General anesthesia with Isoflurane
Arm Type
Active Comparator
Arm Description
Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent.
Intervention Type
Drug
Intervention Name(s)
Total intravenous anesthesia with propofol
Intervention Type
Drug
Intervention Name(s)
General anesthesia with isoflurane
Primary Outcome Measure Information:
Title
Correlation Between Perioperative Change in Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change
Description
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.
Time Frame
Baseline to 6 weeks
Title
Correlation Between Perioperative Change in Ratios of Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change
Description
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.
Time Frame
Baseline to 6 weeks
Secondary Outcome Measure Information:
Title
Continuous Cognitive Index Score Change Difference Between Anesthetic Agent Groups
Description
To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the 10 cognitive test scores from baseline. To quantify overall cognitive function, a baseline cognitive index was first calculated as the mean of the preoperative domain scores. The cognitive index score has a mean of zero, thus any positive score is above the mean, any negative score is below the mean. A continuous change score was then calculated by subtracting the baseline from the 6-week cognitive index. A negative change score indicating decline and a positive score indicating improvement. The resulting outcome measure is unbounded with a standard deviation of 0.31 in the full surgical cohort.
Time Frame
Baseline to 6 weeks
Title
Change in CSF Markers of Alzheimers Disease by Anesthetic Agent Group
Description
CSF Markers of Alzheimer's Disease over time in the subjects treated with propofol versus those treated with isoflurane.
Time Frame
Baseline to 6 weeks
Title
Change in Ratio of CSF Markers of Alzheimers Disease by Anesthetic Agent Group
Description
Change in ratio of CSF Markers of Alzheimer's Disease over time in the subjects treated with propofol versus those treated with isoflurane.
Time Frame
baseline to 6-weeks
Title
Perioperative CSF Tau/Abeta Ratio Change
Description
The perioperative change in the CSF tau/Abeta ratio from the start of anesthesia/surgery to 24 hours later.
Time Frame
Baseline to 24 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miles Berger, MD, PhD
Organizational Affiliation
Duke University Medical Center, Anesthesiology Department, Neuroanesthesia Division
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
35104057
Citation
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.
Results Reference
derived
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Markers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care
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