Markers of Alzheimers Disease After Propofol or Isoflurane Anesthesia

NCT01640275 | Completed Phase 1

• 1 other identifier: Pro00030861
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

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.

Conditions

General Anesthesia

Keywords

General Anesthesia; Alzheimers Disease; Cognitive decline

Outcome Measures

Primary Outcomes (1)

• Ratio of cerebrospinal fluid tau to amyloid beta

  twenty four hours after the induction of anesthesia

Secondary Outcomes (8)

• 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

Study Arms (2)

Propofol based intravenous anesthesia

ACTIVE COMPARATOR

patients will receive propofol based intravenous anesthesia

Drug: Propofol

Isoflurane Based Inhaled Anesthesia

EXPERIMENTAL

patients will receive isoflurane based inhaled anesthesia

Drug: Isoflurane

Interventions

Propofol DRUG

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

Propofol based intravenous anesthesia

Isoflurane DRUG

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

Isoflurane Based Inhaled Anesthesia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27709, United States

Location

Related Publications (2)

• 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.

  PMID: 29181002 DERIVED

• 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.

  PMID: 27079717 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Propofol; Isoflurane

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Methyl Ethers; Ethers

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2012
• First Posted: July 13, 2012
• Study Start: March 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: August 4, 2015

Record last verified: 2015-03

Locations

US (1)