Trial Outcomes & Findings for Markers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care (NCT NCT01993836)
NCT ID: NCT01993836
Last Updated: 2023-03-22
Results Overview
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.
COMPLETED
PHASE4
191 participants
Baseline to 6 weeks
2023-03-22
Participant Flow
Participant milestones
| Measure |
General Anesthesia With Isoflurane
Surgical patients randomized to receive inhalational anesthesia with isoflurane during surgery
|
Total Intravenous Anesthesia With Propofol
Surgical patients randomized to receive intravenous anesthesia with propofol during surgery
|
Non-Surgical Controls
Cohort of community dwelling healthy controls for tertiary comparison
|
|---|---|---|---|
|
Overall Study
STARTED
|
72
|
68
|
51
|
|
Overall Study
COMPLETED
|
55
|
55
|
46
|
|
Overall Study
NOT COMPLETED
|
17
|
13
|
5
|
Reasons for withdrawal
| Measure |
General Anesthesia With Isoflurane
Surgical patients randomized to receive inhalational anesthesia with isoflurane during surgery
|
Total Intravenous Anesthesia With Propofol
Surgical patients randomized to receive intravenous anesthesia with propofol during surgery
|
Non-Surgical Controls
Cohort of community dwelling healthy controls for tertiary comparison
|
|---|---|---|---|
|
Overall Study
Surgery Cancelled
|
3
|
0
|
0
|
|
Overall Study
Physician Decision
|
2
|
1
|
0
|
|
Overall Study
Death
|
0
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
12
|
10
|
5
|
Baseline Characteristics
Markers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care
Baseline characteristics by cohort
| Measure |
General Anesthesia With Isoflurane
n=55 Participants
Surgical patients randomized to receive inhalational anesthesia with isoflurane during surgery
|
Total Intravenous Anesthesia With Propofol
n=55 Participants
Surgical patients randomized to receive iintravenous anesthesia with propofol during surgery
|
Non-Surgical Controls
n=46 Participants
Cohort of community dwelling healthy controls for tertiary comparison
|
Total
n=156 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
68.6 years
STANDARD_DEVIATION 6.1 • n=5 Participants
|
69.7 years
STANDARD_DEVIATION 6.9 • n=7 Participants
|
69.6 years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
69.3 years
STANDARD_DEVIATION 6.8 • n=4 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
59 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
97 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
52 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
135 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
55 participants
n=5 Participants
|
55 participants
n=7 Participants
|
46 participants
n=5 Participants
|
156 participants
n=4 Participants
|
|
Baseline CSF levels
Tau
|
47 pg/ml
n=5 Participants
|
50 pg/ml
n=7 Participants
|
58.5 pg/ml
n=5 Participants
|
49 pg/ml
n=4 Participants
|
|
Baseline CSF levels
Abeta
|
369 pg/ml
n=5 Participants
|
352 pg/ml
n=7 Participants
|
330.5 pg/ml
n=5 Participants
|
347 pg/ml
n=4 Participants
|
|
Baseline CSF levels
P-Tau
|
26 pg/ml
n=5 Participants
|
28 pg/ml
n=7 Participants
|
21.0 pg/ml
n=5 Participants
|
25 pg/ml
n=4 Participants
|
|
Baseline CSF ratio levels
Tau/Abeta Ratio
|
0.13 ratio
n=5 Participants
|
0.14 ratio
n=7 Participants
|
0.16 ratio
n=5 Participants
|
0.14 ratio
n=4 Participants
|
|
Baseline CSF ratio levels
P-Tau/Abeta Ratio
|
0.08 ratio
n=5 Participants
|
0.08 ratio
n=7 Participants
|
0.06 ratio
n=5 Participants
|
0.07 ratio
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to 6 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Combined Surgical Cohort
n=110 Participants
The combination of both surgical randomized treatment groups.
|
General Anesthesia With Isoflurane
Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent.
General anesthesia with isoflurane
|
|---|---|---|
|
Correlation Between Perioperative Change in Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change
Tau
|
-1.21 pg/ml
Interval -26.0 to 32.0
|
—
|
|
Correlation Between Perioperative Change in Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change
Abeta
|
-5.09 pg/ml
Interval -189.0 to 211.0
|
—
|
|
Correlation Between Perioperative Change in Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change
P-Tau
|
-0.44 pg/ml
Interval -31.0 to 85.0
|
—
|
PRIMARY outcome
Timeframe: Baseline to 6 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Combined Surgical Cohort
n=110 Participants
The combination of both surgical randomized treatment groups.
|
General Anesthesia With Isoflurane
Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent.
General anesthesia with isoflurane
|
|---|---|---|
|
Correlation Between Perioperative Change in Ratios of Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change
Tau/Abeta Ratio
|
0.001 ratio
Interval -0.2 to 0.21
|
—
|
|
Correlation Between Perioperative Change in Ratios of Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change
P-Tau/Abeta Ratio
|
0.002 ratio
Interval -0.1 to 0.41
|
—
|
SECONDARY outcome
Timeframe: Baseline to 6 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Combined Surgical Cohort
n=55 Participants
The combination of both surgical randomized treatment groups.
|
General Anesthesia With Isoflurane
n=55 Participants
Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent.
General anesthesia with isoflurane
|
|---|---|---|
|
Continuous Cognitive Index Score Change Difference Between Anesthetic Agent Groups
|
0.019 units on a scale
Standard Error 0.05
|
0.061 units on a scale
Standard Error 0.04
|
SECONDARY outcome
Timeframe: Baseline to 6 weeksPopulation: 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.
CSF Markers of Alzheimer's Disease over time in the subjects treated with propofol versus those treated with isoflurane.
Outcome measures
| Measure |
Combined Surgical Cohort
n=55 Participants
The combination of both surgical randomized treatment groups.
|
General Anesthesia With Isoflurane
n=55 Participants
Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent.
General anesthesia with isoflurane
|
|---|---|---|
|
Change in CSF Markers of Alzheimers Disease by Anesthetic Agent Group
Tau
|
-0.80 pg/ml
Interval -26.0 to 25.0
|
-1.67 pg/ml
Interval -25.0 to 32.0
|
|
Change in CSF Markers of Alzheimers Disease by Anesthetic Agent Group
Abeta
|
-2.10 pg/ml
Interval -189.0 to 211.0
|
-9.50 pg/ml
Interval -127.0 to 158.0
|
|
Change in CSF Markers of Alzheimers Disease by Anesthetic Agent Group
P-Tau
|
-2.25 pg/ml
Interval -31.0 to 49.0
|
1.10 pg/ml
Interval -25.0 to 85.0
|
SECONDARY outcome
Timeframe: baseline to 6-weeksPopulation: 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.
Change in ratio of CSF Markers of Alzheimer's Disease over time in the subjects treated with propofol versus those treated with isoflurane.
Outcome measures
| Measure |
Combined Surgical Cohort
n=55 Participants
The combination of both surgical randomized treatment groups.
|
General Anesthesia With Isoflurane
n=55 Participants
Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent.
General anesthesia with isoflurane
|
|---|---|---|
|
Change in Ratio of CSF Markers of Alzheimers Disease by Anesthetic Agent Group
Tau/Abeta Ratio
|
0.00 ratio
Interval -0.11 to 0.21
|
-0.00 ratio
Interval -0.2 to 0.13
|
|
Change in Ratio of CSF Markers of Alzheimers Disease by Anesthetic Agent Group
P-Tau/Abeta Ratio
|
-0.00 ratio
Interval -0.1 to 0.28
|
0.01 ratio
Interval -0.08 to 0.41
|
SECONDARY outcome
Timeframe: Baseline to 24 hoursPopulation: 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.
The perioperative change in the CSF tau/Abeta ratio from the start of anesthesia/surgery to 24 hours later.
Outcome measures
| Measure |
Combined Surgical Cohort
n=110 Participants
The combination of both surgical randomized treatment groups.
|
General Anesthesia With Isoflurane
Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent.
General anesthesia with isoflurane
|
|---|---|---|
|
Perioperative CSF Tau/Abeta Ratio Change
|
-0.001 ratio
Interval -0.19 to 0.22
|
—
|
Adverse Events
General Anesthesia With Isoflurane
Total Intravenous Anesthesia With Propofol
Non-Surgical Controls
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
General Anesthesia With Isoflurane
n=72 participants at risk
Surgical patients randomized to receive inhalational anesthesia with isoflurane during surgery
|
Total Intravenous Anesthesia With Propofol
n=68 participants at risk
Surgical patients randomized to receive iintravenous anesthesia with propofol during surgery
|
Non-Surgical Controls
n=51 participants at risk
Cohort of community dwelling healthy controls for comparison
|
|---|---|---|---|
|
General disorders
Fever
|
0.00%
0/72 • 6 weeks
|
1.5%
1/68 • Number of events 1 • 6 weeks
|
0.00%
0/51 • 6 weeks
|
|
Nervous system disorders
Headache
|
0.00%
0/72 • 6 weeks
|
1.5%
1/68 • Number of events 1 • 6 weeks
|
0.00%
0/51 • 6 weeks
|
|
Cardiac disorders
Vagal Event
|
1.4%
1/72 • Number of events 1 • 6 weeks
|
4.4%
3/68 • Number of events 3 • 6 weeks
|
3.9%
2/51 • Number of events 2 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of Breath
|
0.00%
0/72 • 6 weeks
|
1.5%
1/68 • Number of events 1 • 6 weeks
|
0.00%
0/51 • 6 weeks
|
|
General disorders
Leg Pain and Swelling
|
1.4%
1/72 • Number of events 1 • 6 weeks
|
0.00%
0/68 • 6 weeks
|
0.00%
0/51 • 6 weeks
|
|
Nervous system disorders
Post-dural puncture headache
|
0.00%
0/72 • 6 weeks
|
1.5%
1/68 • Number of events 1 • 6 weeks
|
3.9%
2/51 • Number of events 2 • 6 weeks
|
|
General disorders
Back Pain
|
0.00%
0/72 • 6 weeks
|
1.5%
1/68 • Number of events 1 • 6 weeks
|
5.9%
3/51 • Number of events 5 • 6 weeks
|
|
Blood and lymphatic system disorders
Elevated PTT
|
0.00%
0/72 • 6 weeks
|
1.5%
1/68 • Number of events 1 • 6 weeks
|
0.00%
0/51 • 6 weeks
|
|
General disorders
Neck Stiffness
|
0.00%
0/72 • 6 weeks
|
1.5%
1/68 • Number of events 1 • 6 weeks
|
0.00%
0/51 • 6 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place