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

Primary Purpose

General Anesthesia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Propofol
Isoflurane
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for General Anesthesia focused on measuring General Anesthesia, Alzheimers Disease, Cognitive decline

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Duke University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Propofol based intravenous anesthesia

Isoflurane Based Inhaled Anesthesia

Arm Description

patients will receive propofol based intravenous anesthesia

patients will receive isoflurane based inhaled anesthesia

Outcomes

Primary Outcome Measures

Ratio of cerebrospinal fluid tau to amyloid beta

Secondary Outcome Measures

the relationship between anesthetic exposure and CSF biomarker changes
the relationship between anesthetic exposure and CSF biomarker changes, and demographics (age, gender, and race)
the relationship between CSF biomarker changes and serum markers of metabolic and/or inflammatory status
the relationship between anesthetic exposure and biomarker changes and serum markers of metabolic and/or inflammatory status
the relationship between anesthetic exposure and biomarker changes and neuroimaging results obtained as dictated by routine standard of care
the relationship between anesthetic exposure and biomarker changes and depth of anesthesia, based on average BIS (bispectral index) monitoring signal
the relationship between anesthetic exposure and biomarker changes and the time of day that surgery is performed
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

Full Information

First Posted
June 20, 2012
Last Updated
August 3, 2015
Sponsor
Duke University
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1. Study Identification

Unique Protocol Identification Number
NCT01640275
Brief Title
Markers of Alzheimers Disease After Propofol or Isoflurane Anesthesia
Acronym
MAD-PIA
Official Title
The Effect of Isoflurane Versus Propofol Anesthesia on Alzheimers Disease CSF Markers
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
General Anesthesia
Keywords
General Anesthesia, Alzheimers Disease, Cognitive decline

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
105 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Propofol based intravenous anesthesia
Arm Type
Active Comparator
Arm Description
patients will receive propofol based intravenous anesthesia
Arm Title
Isoflurane Based Inhaled Anesthesia
Arm Type
Experimental
Arm Description
patients will receive isoflurane based inhaled anesthesia
Intervention Type
Drug
Intervention Name(s)
Propofol
Intervention Description
patients randomized to the propofol arm of the study will receive general anesthesia with propofol
Intervention Type
Drug
Intervention Name(s)
Isoflurane
Intervention Description
patients randomized to the isoflurane arm of the study will receive general anesthesia with isoflurane
Primary Outcome Measure Information:
Title
Ratio of cerebrospinal fluid tau to amyloid beta
Time Frame
twenty four hours after the induction of anesthesia
Secondary Outcome Measure Information:
Title
the relationship between anesthetic exposure and CSF biomarker changes
Time Frame
up to 24 hrs after induction of anesthesia
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miles Berger, MD, PhD
Organizational Affiliation
Duke University Medical Center, Department of Anesthesiology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael L James, MD
Organizational Affiliation
Duke University Medical Center, Department of Anesthesiology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David McDonagh, MD
Organizational Affiliation
Duke University Medical Center, Department of Anesthesiology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27709
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29181002
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.
Results Reference
derived
PubMed Identifier
27079717
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.
Results Reference
derived

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Markers of Alzheimers Disease After Propofol or Isoflurane Anesthesia

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