Clinical trial NCT01640275: Markers of Alzheimers Disease After Propofol or Isoflurane Anesthesia
Official title: The Effect of Isoflurane Versus Propofol Anesthesia on Alzheimers Disease CSF Markers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: General Anesthesia
Keywords: General Anesthesia
Alzheimers Disease
Cognitive decline
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2012-07-13
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Ratio of cerebrospinal fluid tau to amyloid beta
timeFrame: twenty four hours after the induction of anesthesia
Secondary outcomes:
measure: the relationship between anesthetic exposure and CSF biomarker changes
timeFrame: up to 24 hrs after induction of anesthesia
measure: the relationship between anesthetic exposure and CSF biomarker changes, and demographics (age, gender, and race)
timeFrame: up to 24 hrs after induction of anesthesia
measure: the relationship between CSF biomarker changes and serum markers of metabolic and/or inflammatory status
timeFrame: up to 24 hrs after induction of anesthesia
measure: the relationship between anesthetic exposure and biomarker changes and serum markers of metabolic and/or inflammatory status
timeFrame: up to 24 hrs after induction of anesthesia
measure: the relationship between anesthetic exposure and biomarker changes and neuroimaging results obtained as dictated by routine standard of care
timeFrame: up to 24 hours after induction of anesthesia
measure: the relationship between anesthetic exposure and biomarker changes and depth of anesthesia, based on average BIS (bispectral index) monitoring signal
timeFrame: up to 24 hours after induction of anesthesia
measure: the relationship between anesthetic exposure and biomarker changes and the time of day that surgery is performed
timeFrame: up to 24 hours after induction of anesthesia
measure: 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
timeFrame: up to 24 hours after induction of anesthesia
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University Medical Center, Department of Anesthesiology
name: Miles Berger, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University Medical Center, Department of Anesthesiology
name: Michael L James, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University Medical Center, Department of Anesthesiology
name: David McDonagh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Berger 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.