MAD-PIA: Markers of Alzheimers Disease After Propofol or Isoflurane Anesthesia

Sponsor

Duke University (Other)

Overall Status

Completed

CT.gov ID

NCT01640275

Collaborator

(none)

105

Enrollment

Location

Arms

Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
General Anesthesia	Drug: Propofol Drug: Isoflurane	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

105 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Diagnostic

Official Title:

The Effect of Isoflurane Versus Propofol Anesthesia on Alzheimers Disease CSF Markers

Study Start Date :

Mar 1, 2012

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Propofol based intravenous anesthesia patients will receive propofol based intravenous anesthesia	Drug: Propofol patients randomized to the propofol arm of the study will receive general anesthesia with propofol
Experimental: Isoflurane Based Inhaled Anesthesia patients will receive isoflurane based inhaled anesthesia	Drug: Isoflurane patients randomized to the isoflurane arm of the study will receive general anesthesia with isoflurane

Arm

Intervention/Treatment

Active Comparator: Propofol based intravenous anesthesia

patients will receive propofol based intravenous anesthesia

Drug: Propofol

patients randomized to the propofol arm of the study will receive general anesthesia with propofol

Experimental: Isoflurane Based Inhaled Anesthesia

patients will receive isoflurane based inhaled anesthesia

Drug: Isoflurane

patients randomized to the isoflurane arm of the study will receive general anesthesia with isoflurane

Outcome Measures

Primary Outcome Measures

Ratio of cerebrospinal fluid tau to amyloid beta [twenty four hours after the induction of anesthesia]

Secondary Outcome Measures

the relationship between anesthetic exposure and CSF biomarker changes [up to 24 hrs after induction of anesthesia]
the relationship between anesthetic exposure and CSF biomarker changes, and demographics (age, gender, and race) [up to 24 hrs after induction of anesthesia]
the relationship between CSF biomarker changes and serum markers of metabolic and/or inflammatory status [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 [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 [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 [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 [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 [up to 24 hours after induction of anesthesia]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27709

Sponsors and Collaborators

Duke University

Investigators

Principal Investigator: Miles Berger, MD, PhD, Duke University Medical Center, Department of Anesthesiology
Principal Investigator: Michael L James, MD, Duke University Medical Center, Department of Anesthesiology
Principal Investigator: David McDonagh, MD, Duke University Medical Center, Department of Anesthesiology