Alzheimers DiseasePhase 4MADCO-PCNCT01993836
Markers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care
A Phase 4 study testing Total intravenous anesthesia with propofol and General anesthesia with isoflurane in people with Alzheimers Disease and Postoperative Delirium, run by Duke University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Alzheimers Disease, Postoperative Delirium, Post Operative Cognitive Dysfunction
- What is being tested?
- Total intravenous anesthesia with propofol and General anesthesia with isoflurane
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 191 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2013to 10 Jan 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
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.
- Being tested
- Total intravenous anesthesia with propofol, General anesthesia with isoflurane
- Keywords
- isoflurane, propofol, total intravenous anesthesia, inhaled anesthetic, volatile anesthetic, anesthesia, delirium, Post Operative Cognitive Dysfunction, Alzheimer's Disease, Mild Cognitive Impairment
- Medical subject headings
- Alzheimer Disease, Emergence Delirium, Delirium, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total intravenous anesthesia with propofolDrug
General anesthesia with isofluraneDrug
| Study group | Role | What they receive |
|---|---|---|
| Total Intravenous Anesthesia with Propofol | Active comparator | Patients in this arm will receive general anesthesia with propofol as the primary amnestic agent. Receives: 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. Receives: Drug: General anesthesia with isoflurane |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline to 6 weeks
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2013 (estimated)
- Study startNov 2013
- Primary completion10 Jan 2019
- Study completion10 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimers DiseaseStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 191 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Miles Berger, MD, PhD, Principal investigator, Duke University Medical Center, Anesthesiology Department, Neuroanesthesia Division
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01993836
- Sponsor's protocol ID
- Pro00045180
- Acronym
- MADCO-PC
- Status last verified
- Mar 2023
- First submitted
- 15 Nov 2013
- Last updated
- 22 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 37271721Berger 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.
PubMed 35104057
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Markers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care
- ClinicalTrials.gov ID
- NCT01993836
- Acronym / sponsor ID
- MADCO-PC / Pro00045180
- Keywords
- isoflurane, propofol, total intravenous anesthesia, inhaled anesthetic, volatile anesthetic, anesthesia, delirium, Post Operative Cognitive Dysfunction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 191 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- Nov 2013 (actual)
- Primary completion
- 10 Jan 2019 (actual)
- Study completion
- 10 Jan 2019 (actual)
- First posted
- 25 Nov 2013 (estimated)
- Results
- Posted 5 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Total Intravenous Anesthesia with Propofol | Active comparator | Drug: Total intravenous anesthesia with propofolPatients in this arm will receive general anesthesia with propofol as the primary amnestic agent. |
| General anesthesia with Isoflurane | Active comparator | Drug: General anesthesia with isofluranePatients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Total intravenous anesthesia with propofol | Drug | Total Intravenous Anesthesia with Propofol |
| General anesthesia with isoflurane | Drug | General anesthesia with Isoflurane |
Primary outcome
Correlation Between Perioperative Change in Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change
Time frame: Baseline to 6 weeks
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
Time frame: Baseline to 6 weeks
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.
4 secondary outcomes
Continuous Cognitive Index Score Change Difference Between Anesthetic Agent Groups
Time frame: Baseline to 6 weeks
Change in CSF Markers of Alzheimers Disease by Anesthetic Agent Group
Time frame: Baseline to 6 weeks
Change in Ratio of CSF Markers of Alzheimers Disease by Anesthetic Agent Group
Time frame: baseline to 6-weeks
Perioperative CSF Tau/Abeta Ratio Change
Time frame: Baseline to 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37271721Villalobos 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.
- Derived from this study: PubMed 35104057Berger 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.
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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.
Miles Berger, MD, PhD principal investigator
Duke University Medical Center, Anesthesiology Department, Neuroanesthesia Division
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Total intravenous anesthesia with propofol and General anesthesia with isoflurane in people with Alzheimers Disease and Postoperative Delirium, run by Duke University at 1 site 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 4 inclusion and 4 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: finished, as of the sponsor's last update on 22 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Correlation Between Perioperative Change in Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change (time frame: Baseline to 6 weeks). The study lists 2 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 NCT01993836, which also lists 2 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 22 Mar 2023.