General AnesthesiaPhase 1MAD-PIANCT01640275
Markers of Alzheimers Disease After Propofol or Isoflurane Anesthesia
A Phase 1 study testing Propofol and Isoflurane in people with General Anesthesia, run by Duke University at 1 site in United States.
Trial summary
Previous work in animal models suggests that inhalational anesthetic agents may accelerate Alzheimer's disease pathogenesis, but it is unclear to what extent this may happen in humans. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- General Anesthesia
- What is being tested?
- Propofol and Isoflurane
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Mar 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age 18 and above
- seen in neurosurgical clinic, and scheduled for operative aneurysm repair or other neurosurgical procedure necessitating lumbar drain placement.
- ability to speak English.
- ability to understand consent forms, and to give informed consent.
Who cannot join
- age less than 18
- lumbar drain is not placed
- not eligible for one of the anesthetics (inhaled isoflurane or IV propofol)
- inmate of a correctional facility (i.e. prisoners).
- pregnancy. Pregnancy is ruled out as standard of care before cranial surgery, based on clinical history and/or HCG testing
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27709
About this study
Official title: The Effect of Isoflurane Versus Propofol Anesthesia on Alzheimers Disease CSF Markers
Previous work in animal models suggests that inhalational anesthetic agents may accelerate Alzheimer's disease pathogenesis, but it is unclear to what extent this may happen in humans. Here, the investigators propose to measure Alzheimer's disease-related neural markers in the cerebrospinal fluid (CSF) of patients exposed to anesthesia while undergoing neurosurgical procedures that require lumbar drain placement. Patients will be randomized to either receive inhalation anesthesia with isoflurane or intravenous anesthesia with propofol.
CSF and blood samples will each be collected at the induction of anesthesia, and then again ten and twenty-four hours later. CSF samples will be assayed for amyloid beta, tau, and other Alzheimer's disease-associated markers; blood samples will be assayed for serum inflammatory markers and used for genotyping studies. These studies should clarify the effect of common anesthetic agents on Alzheimer's disease related neural markers.
- Conditions
- General Anesthesia
- Being tested
- Propofol, Isoflurane
- Keywords
- General Anesthesia, Alzheimers Disease, Cognitive decline
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropofolDrug
patients randomized to the propofol arm of the study will receive general anesthesia with propofol
IsofluraneDrug
patients randomized to the isoflurane arm of the study will receive general anesthesia with isoflurane
| Study group | Role | What they receive |
|---|---|---|
| Propofol based intravenous anesthesia | Active comparator | patients will receive propofol based intravenous anesthesia Receives: Drug: Propofol |
| Isoflurane Based Inhaled Anesthesia | Experimental | patients will receive isoflurane based inhaled anesthesia Receives: Drug: Isoflurane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of cerebrospinal fluid tau to amyloid beta
Measured: twenty four hours after the induction of anesthesia
Secondary outcomes (8)
the relationship between anesthetic exposure and CSF biomarker changes
Measured: up to 24 hrs after induction of anesthesia
the relationship between anesthetic exposure and CSF biomarker changes, and demographics (age, gender, and race)
Measured: up to 24 hrs after induction of anesthesia
the relationship between CSF biomarker changes and serum markers of metabolic and/or inflammatory status
Measured: up to 24 hrs after induction of anesthesia
the relationship between anesthetic exposure and biomarker changes and serum markers of metabolic and/or inflammatory status
Measured: up to 24 hrs after induction of anesthesia
the relationship between anesthetic exposure and biomarker changes and neuroimaging results obtained as dictated by routine standard of care
Measured: up to 24 hours after induction of anesthesia
the relationship between anesthetic exposure and biomarker changes and depth of anesthesia, based on average BIS (bispectral index) monitoring signal
Measured: up to 24 hours after induction of anesthesia
the relationship between anesthetic exposure and biomarker changes and the time of day that surgery is performed
Measured: up to 24 hours after induction of anesthesia
the relationship between anesthetic exposure and biomarker changes with genetic polymorphisms in ApoE (apolipoprotein E) and other genes related to inflammation, metabolism, brain function and/or Alzheimer's disease
Measured: up to 24 hours after induction of anesthesia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2012 (estimated)
- Study startMar 2012
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for General AnesthesiaStudies 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 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 105 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, Department of AnesthesiologyMichael L James, MD, Principal investigator, Duke University Medical Center, Department of AnesthesiologyDavid McDonagh, MD, Principal investigator, Duke University Medical Center, Department of Anesthesiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01640275
- Sponsor's protocol ID
- Pro00030861
- Acronym
- MAD-PIA
- Status last verified
- Mar 2015
- First submitted
- 20 Jun 2012
- Last updated
- 4 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Berger M, Ponnusamy V, Greene N, Cooter M, Nadler JW, Friedman A, McDonagh DL, Laskowitz DT, Newman MF, Shaw LM, Warner DS, Mathew JP, James ML; MAD-PIA Investigators. The Effect of Propofol vs. Isoflurane Anesthesia on Postoperative Changes in Cerebrospinal Fluid Cytokine Levels: Results from a Randomized Trial. Front Immunol. 2017 Nov 13;8:1528. doi: 10.3389/fimmu.2017.01528. eCollection 2017.
PubMed 29181002Berger M, Nadler JW, Friedman A, McDonagh DL, Bennett ER, Cooter M, Qi W, Laskowitz DT, Ponnusamy V, Newman MF, Shaw LM, Warner DS, Mathew JP, James ML; MAD-PIA trial team. The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial. J Alzheimers Dis. 2016 Apr 15;52(4):1299-310. doi: 10.3233/JAD-151190.
PubMed 27079717
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Isoflurane Versus Propofol Anesthesia on Alzheimers Disease CSF Markers
- ClinicalTrials.gov ID
- NCT01640275
- Acronym / sponsor ID
- MAD-PIA / Pro00030861
- Conditions
- General Anesthesia
- Keywords
- General Anesthesia, Alzheimers Disease, Cognitive decline
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 13 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Previous work in animal models suggests that inhalational anesthetic agents may accelerate Alzheimer's disease pathogenesis, but it is unclear to what extent this may happen in humans. Here, the investigators propose to measure Alzheimer's disease-related neural markers in the cerebrospinal fluid (CSF) of patients exposed to anesthesia while undergoing neurosurgical procedures that require lumbar drain placement. Patients will be randomized to either receive inhalation anesthesia with isoflurane or intravenous anesthesia with propofol.
CSF and blood samples will each be collected at the induction of anesthesia, and then again ten and twenty-four hours later. CSF samples will be assayed for amyloid beta, tau, and other Alzheimer's disease-associated markers; blood samples will be assayed for serum inflammatory markers and used for genotyping studies. These studies should clarify the effect of common anesthetic agents on Alzheimer's disease related neural markers.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Propofol based intravenous anesthesia | Active comparator | Drug: Propofolpatients will receive propofol based intravenous anesthesia |
| Isoflurane Based Inhaled Anesthesia | Experimental | Drug: Isofluranepatients will receive isoflurane based inhaled anesthesia |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- age 18 and above
- seen in neurosurgical clinic, and scheduled for operative aneurysm repair or other neurosurgical procedure necessitating lumbar drain placement.
- ability to speak English.
- ability to understand consent forms, and to give informed consent.
Key exclusion criteria (5 listed)
- age less than 18
- lumbar drain is not placed
- not eligible for one of the anesthetics (inhaled isoflurane or IV propofol)
- inmate of a correctional facility (i.e. prisoners).
- pregnancy. Pregnancy is ruled out as standard of care before cranial surgery, based on clinical history and/or HCG testing
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 |
|---|---|---|
| Propofolpatients randomized to the propofol arm of the study will receive general anesthesia with propofol | Drug | Propofol based intravenous anesthesia |
| Isofluranepatients randomized to the isoflurane arm of the study will receive general anesthesia with isoflurane | Drug | Isoflurane Based Inhaled Anesthesia |
Primary outcome
Ratio of cerebrospinal fluid tau to amyloid beta
Time frame: twenty four hours after the induction of anesthesia
8 secondary outcomes
the relationship between anesthetic exposure and CSF biomarker changes
Time frame: up to 24 hrs after induction of anesthesia
the relationship between anesthetic exposure and CSF biomarker changes, and demographics (age, gender, and race)
Time frame: up to 24 hrs after induction of anesthesia
the relationship between CSF biomarker changes and serum markers of metabolic and/or inflammatory status
Time frame: up to 24 hrs after induction of anesthesia
the relationship between anesthetic exposure and biomarker changes and serum markers of metabolic and/or inflammatory status
Time frame: up to 24 hrs after induction of anesthesia
the relationship between anesthetic exposure and biomarker changes and neuroimaging results obtained as dictated by routine standard of care
Time frame: up to 24 hours after induction of anesthesia
the relationship between anesthetic exposure and biomarker changes and depth of anesthesia, based on average BIS (bispectral index) monitoring signal
Time frame: up to 24 hours after induction of anesthesia
the relationship between anesthetic exposure and biomarker changes and the time of day that surgery is performed
Time frame: up to 24 hours after induction of anesthesia
the relationship between anesthetic exposure and biomarker changes with genetic polymorphisms in ApoE (apolipoprotein E) and other genes related to inflammation, metabolism, brain function and/or Alzheimer's disease
Time frame: up to 24 hours after induction of anesthesia
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2015.
- Derived from this study: PubMed 29181002Berger M, Ponnusamy V, Greene N, Cooter M, Nadler JW, Friedman A, McDonagh DL, Laskowitz DT, Newman MF, Shaw LM, Warner DS, Mathew JP, James ML; MAD-PIA Investigators. The Effect of Propofol vs. Isoflurane Anesthesia on Postoperative Changes in Cerebrospinal Fluid Cytokine Levels: Results from a Randomized Trial. Front Immunol. 2017 Nov 13;8:1528. doi: 10.3389/fimmu.2017.01528. eCollection 2017.
- Derived from this study: PubMed 27079717Berger M, Nadler JW, Friedman A, McDonagh DL, Bennett ER, Cooter M, Qi W, Laskowitz DT, Ponnusamy V, Newman MF, Shaw LM, Warner DS, Mathew JP, James ML; MAD-PIA trial team. The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial. J Alzheimers Dis. 2016 Apr 15;52(4):1299-310. doi: 10.3233/JAD-151190.
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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, Department of Anesthesiology
Michael L James, MD principal investigator
Duke University Medical Center, Department of Anesthesiology
David McDonagh, MD principal investigator
Duke University Medical Center, Department of Anesthesiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Propofol and Isoflurane in people with General Anesthesia, 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 5 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 4 Aug 2015. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Ratio of cerebrospinal fluid tau to amyloid beta (time frame: twenty four hours after the induction of anesthesia). 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 NCT01640275, 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 4 Aug 2015.