Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Total Intravenous Anesthesia with Propofol | Active Comparator | Patients in this arm will receive general anesthesia with propofol as the primary amnestic agent. |
|
| General anesthesia with Isoflurane | Active Comparator | Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Total intravenous anesthesia with propofol | Drug |
| ||
| General anesthesia with isoflurane |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Miles Berger, MD, PhD | Duke University Medical Center, Anesthesiology Department, Neuroanesthesia Division | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37271721 | Derived | 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. | |
| 35104057 |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | General Anesthesia With Isoflurane | Surgical patients randomized to receive inhalational anesthesia with isoflurane during surgery |
| FG001 | Total Intravenous Anesthesia With Propofol | Surgical patients randomized to receive intravenous anesthesia with propofol during surgery |
| FG002 | Non-Surgical Controls | Cohort of community dwelling healthy controls for tertiary comparison |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Subjects who returned for six-week follow-up visit.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | General Anesthesia With Isoflurane | Surgical patients randomized to receive inhalational anesthesia with isoflurane during surgery |
| BG001 | Total Intravenous Anesthesia With Propofol |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Analysis for the primary and secondary outcome 6 use the combination of both randomized treatment groups. The treatment groups are separated and compared in secondary analysis of outcomes 3-5, and the control group is only used in tertiary analyses. To be included in the outcome analysis patients must have returned for six-week follow-up visit. | Posted | Median | Full Range | pg/ml | Baseline to 6 weeks |
|
6 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | General Anesthesia With Isoflurane | Surgical patients randomized to receive inhalational anesthesia with isoflurane during surgery |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fever | General disorders | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Miles Berger, MD, PhD | Duke University | 919-684-8679 | miles.berger@duke.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 15, 2016 | Mar 20, 2023 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 5, 2017 | Mar 20, 2023 | SAP_002.pdf |
Not provided
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D000071257 | Emergence Delirium |
| D003693 | Delirium |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D015742 | Propofol |
| D000768 | Anesthesia, General |
| D007530 | Isoflurane |
| ID | Term |
|---|---|
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
|
| Baseline to 6 weeks |
| 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. | Baseline to 6 weeks |
| 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. | baseline to 6-weeks |
| 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. | Baseline to 24 hours |
| Derived |
| 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. |
| Death |
|
| Withdrawal by Subject |
|
Surgical patients randomized to receive iintravenous anesthesia with propofol during surgery
| BG002 | Non-Surgical Controls | Cohort of community dwelling healthy controls for tertiary comparison |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Baseline CSF levels | Median | Full Range | pg/ml |
|
| Baseline CSF ratio levels | Median | Full Range | ratio |
|
The combination of both surgical randomized treatment groups.
|
|
|
| Primary | 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. | Analysis for the primary and secondary outcome 6 use the combination of both randomized treatment groups. The treatment groups are separated and compared in secondary analysis of outcomes 3-5, and the control group is only used in tertiary analyses. To be included in the outcome analysis patients must have returned for six-week follow-up visit. | Posted | Median | Full Range | ratio | Baseline to 6 weeks |
|
|
|
|
| Secondary | 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. | Analysis for the primary and secondary outcome 6 use the combination of both randomized treatment groups. The treatment groups are separated and compared in secondary analysis of outcomes 3-5, and the control group is only used in tertiary analyses. To be included in the outcome analysis patients must have returned for six-week follow-up visit. | Posted | Mean | Standard Error | units on a scale | Baseline to 6 weeks |
|
|
|
|
| Secondary | 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. | Analysis for the primary and secondary outcome 6 use the combination of both randomized treatment groups. The treatment groups are separated and compared in secondary analysis of outcomes 3-5, and the control group is only used in tertiary analyses. To be included in the outcome analysis patients must have returned for six-week follow-up visit. | Posted | Median | Full Range | pg/ml | Baseline to 6 weeks |
|
|
|
|
| Secondary | 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. | Analysis for the primary and secondary outcome 6 use the combination of both randomized treatment groups. The treatment groups are separated and compared in secondary analysis of outcomes 3-5, and the control group is only used in tertiary analyses. To be included in the outcome analysis patients must have returned for six-week follow-up visit. | Posted | Median | Full Range | ratio | baseline to 6-weeks |
|
|
|
|
| Secondary | 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. | Analysis for the primary and secondary outcome 6 use the combination of both randomized treatment groups. The treatment groups are separated and compared in secondary analysis of outcomes 3-5, and the control group is only used in tertiary analyses. To be included in the outcome analysis patients must have returned for six-week follow-up visit. | Posted | Median | Full Range | ratio | Baseline to 24 hours |
|
|
|
|
| 0 |
| 72 |
| 0 |
| 72 |
| 2 |
| 72 |
| EG001 | Total Intravenous Anesthesia With Propofol | Surgical patients randomized to receive iintravenous anesthesia with propofol during surgery | 2 | 68 | 0 | 68 | 8 | 68 |
| EG002 | Non-Surgical Controls | Cohort of community dwelling healthy controls for comparison | 0 | 51 | 0 | 51 | 7 | 51 |
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Vagal Event | Cardiac disorders | Non-systematic Assessment |
|
| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Leg Pain and Swelling | General disorders | Non-systematic Assessment |
|
| Post-dural puncture headache | Nervous system disorders | Non-systematic Assessment |
|
| Back Pain | General disorders | Non-systematic Assessment |
|
| Elevated PTT | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Neck Stiffness | General disorders | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003221 | Confusion |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D003072 | Cognition Disorders |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D000758 | Anesthesia |
| D000760 | Anesthesia and Analgesia |
| D008738 | Methyl Ethers |
| D004987 | Ethers |
| Spearman Correlation |
| 0.16 |
| 2-Sided |
| 95 |
| -0.05 |
| 0.34 |
| Other |
| P-Tau |
|
| 0.565 |
| Other |
| Difference in 6-week P-Tau Change between anesthetic groups | Wilcoxon (Mann-Whitney) | 0.110 | Other |
| 0.082 |
| Other |