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Effects of Brain Beta-Amyloid on Postoperative Cognition

Primary Purpose

Postoperative Cognitive Dysfunction

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Florbetapir F 18 (18F-AV-45)
no intervention
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Postoperative Cognitive Dysfunction focused on measuring Postoperative Cognitive Dysfunction, Postoperative Cognitive Decline, POCD, Alzheimer's disease, Florbetapir F 18 (18F-AV-45)

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Scheduled for total knee arthroplasty or total hip arthroplasty under general anesthesia (primary arthroplasties and revisions)
  • English speaking
  • Anticipated stay in the hospital
  • Not anticipated to stay intubated postoperatively
  • Patients who live with or have regular visits from an individual ("study partner") willing to provide information about the patient's cognitive status
  • Willing and able to undergo all testing procedures including neuroimaging and agree to longitudinal follow up
  • Adequate visual and auditory acuity to allow neuropsychological testing
  • Subjects with Clinical Dementia Rating Scale (CDR) of 0-0.5
  • Patients who are not demented
  • Subjects sho signed an IRB approved informed consent prior to any study procedures

Exclusion Criteria:

  • Clinically significant hepatic, renal, pulmonary, metabolic, or endocrine disturbances as indicated by history, which in the opinion of the investigator might pose a potential safety risk to the subject
  • Current clinically significant cardiovascular disease.
  • History of drug or alcohol abuse within the last year, or prior prolonged history of abuse
  • Clinically significant infections disease, including Acquired Immune Deficiency Syndrome (AIDS) or Human Immunodeficiency Virus (HIV) infection or previous positive test for hepatitis
  • History of relevant severe drug allergy or hypersensitivity
  • Received an investigational medication under an FDA IND protocol within the last 30 days.
  • Current clinically significant unstable medical comorbidities, as indicated by history or physical exam, that pose a potential safety risk to the subject
  • Received a radiopharmaceutical for imaging or therapy within the past 24 hours prior to the imaging session for this study
  • Severe psychiatric disorders including schizophrenia, bipolar disorders, and major depression as described in DSM-IV within the past year (medical record, GDS score, interview with the patient and study partner)
  • Obvious causes for their cognitive impairment (e.g. onset coincides with recent head trauma or stroke)
  • Dementia of any cause
  • CDR score > 0.5
  • Expressed the preference to undergo the procedure under regional anesthesia in form of spinal or epidural anesthesia
  • Patients who, in the opinion of the investigator, are otherwise unsuitable for a study of this type

Sites / Locations

  • San Francisco VA Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Surgical Group

Non-surgical group

Arm Description

Subjects scheduled to undergo total knee or total hip replacement at the SFVAMC. Subjects in this arm of the study will undergo the florbetapir PET scan once prior to their surgery. Subjects in this arm of the study will undergo serial neurocognitive assessment, heart rate variability measurement, and blood draws for genetic and inflammatory markers.

Subjects being seen in at the SFVAMC orthopedic clinic for knee or hip pain but are not anticipating surgical intervention. Subjects in this arm will not undergo the florbetapir PET scan. Subjects in this arm of the study will undergo serial neurocognitive assessment, heart rate variability measurement, and blood draws for genetic and inflammatory markers.

Outcomes

Primary Outcome Measures

Cognitive Decline
Measured using comprehensive neurocognitive test battery

Secondary Outcome Measures

Genetic Polymorphisms
Measured by obtaining blood sample
Vagus nerve tone assessment
Measured using Heart Rate Variability (HRV)
Inflammatory Markers
Measured by obtaining blood samples
Perioperative Complications
Measured using patient medical records
Delirium
Measured using the Confusion Assessment Method rating scale (CAM) or the CAM-ICU if admitted to the intensive care unit
Coma Assessment
Measured using the Richmond Agitation Sedation Scale (RASS)
Hospital Length of Stay
Measured using patient medical records
Postoperative Complications
Measured using patient medical records
Change in Cognition
Measured using comprehensive neurocognitive test battery
Quality of Life
Measured by assessing functional status using the Functional Activities Questionnaire and depression using the Geriatric Depression Scale
Mortality
Measured using patient medical records
Pain intensity
Measured using the Numerical Rating Scale
Pain unpleasantness
Measured using the Numerical Rating Scale
Post-traumatic Stress Disorder symptomatology
Measured using the PTSD Checklist

Full Information

First Posted
May 23, 2012
Last Updated
December 16, 2022
Sponsor
University of California, San Francisco
Collaborators
Alzheimer's Drug Discovery Foundation, Avid Radiopharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01606488
Brief Title
Effects of Brain Beta-Amyloid on Postoperative Cognition
Official Title
Effects of Brain Beta Amyloid on Postoperative Cognition and 18F-AV-45-A14: Clinical Evaluation of Florbetapir F 18 (18F-AV-45)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 2012 (undefined)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
June 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Alzheimer's Drug Discovery Foundation, Avid Radiopharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Postoperative cognitive decline (POCD) affects up to 50% of non-cardiac surgical patients greater than or equal to 65 years of age. This study will test the hypothesis that preoperative presence of brain beta-amyloid plaques in non-demented subjects increases postoperative cognitive decline (POCD) in elderly subjects scheduled for hip or knee replacement. The investigators hypothesize that preoperative beta-amyloid plaques will predict postoperative cognitive decline.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postoperative Cognitive Dysfunction
Keywords
Postoperative Cognitive Dysfunction, Postoperative Cognitive Decline, POCD, Alzheimer's disease, Florbetapir F 18 (18F-AV-45)

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Surgical Group
Arm Type
Other
Arm Description
Subjects scheduled to undergo total knee or total hip replacement at the SFVAMC. Subjects in this arm of the study will undergo the florbetapir PET scan once prior to their surgery. Subjects in this arm of the study will undergo serial neurocognitive assessment, heart rate variability measurement, and blood draws for genetic and inflammatory markers.
Arm Title
Non-surgical group
Arm Type
Other
Arm Description
Subjects being seen in at the SFVAMC orthopedic clinic for knee or hip pain but are not anticipating surgical intervention. Subjects in this arm will not undergo the florbetapir PET scan. Subjects in this arm of the study will undergo serial neurocognitive assessment, heart rate variability measurement, and blood draws for genetic and inflammatory markers.
Intervention Type
Drug
Intervention Name(s)
Florbetapir F 18 (18F-AV-45)
Other Intervention Name(s)
Florbetapir, Amyvid 18F-AV-45
Intervention Description
Single IV bolus injection of 370 MBq (10mCi) florbetapir will be administered approximately 50 minutes prior to a 10 minute PET scan.
Intervention Type
Other
Intervention Name(s)
no intervention
Primary Outcome Measure Information:
Title
Cognitive Decline
Description
Measured using comprehensive neurocognitive test battery
Time Frame
At the time of discharge (or at the latest on the 7th postoperative day)
Secondary Outcome Measure Information:
Title
Genetic Polymorphisms
Description
Measured by obtaining blood sample
Time Frame
Participants will be followed from preoperative baseline to 1 year postoperative
Title
Vagus nerve tone assessment
Description
Measured using Heart Rate Variability (HRV)
Time Frame
Participants will be followed from preoperative baseline to 1 year postoperative
Title
Inflammatory Markers
Description
Measured by obtaining blood samples
Time Frame
Participants will be followed from preoperative baseline to 1 year postoperative
Title
Perioperative Complications
Description
Measured using patient medical records
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 1 week
Title
Delirium
Description
Measured using the Confusion Assessment Method rating scale (CAM) or the CAM-ICU if admitted to the intensive care unit
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 1 week
Title
Coma Assessment
Description
Measured using the Richmond Agitation Sedation Scale (RASS)
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 1 week
Title
Hospital Length of Stay
Description
Measured using patient medical records
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 1 week
Title
Postoperative Complications
Description
Measured using patient medical records
Time Frame
Participants will be followed from preoperative baseline to 1 year postoperative
Title
Change in Cognition
Description
Measured using comprehensive neurocognitive test battery
Time Frame
Participants will be followed from preoperative baseline to 1 year postoperative
Title
Quality of Life
Description
Measured by assessing functional status using the Functional Activities Questionnaire and depression using the Geriatric Depression Scale
Time Frame
Participants will be followed from preoperative baseline to 1 year postoperative
Title
Mortality
Description
Measured using patient medical records
Time Frame
Participants will be followed from preoperative baseline to 1 year postoperative
Title
Pain intensity
Description
Measured using the Numerical Rating Scale
Time Frame
Participants will be followed from preoperative baseline to 1 year postoperative
Title
Pain unpleasantness
Description
Measured using the Numerical Rating Scale
Time Frame
Participants will be followed from preoperative baseline to 1 year postoperative
Title
Post-traumatic Stress Disorder symptomatology
Description
Measured using the PTSD Checklist
Time Frame
Participants will be followed from preoperative baseline to 1 year postoperative

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Scheduled for total knee arthroplasty or total hip arthroplasty under general anesthesia (primary arthroplasties and revisions) English speaking Anticipated stay in the hospital Not anticipated to stay intubated postoperatively Patients who live with or have regular visits from an individual ("study partner") willing to provide information about the patient's cognitive status Willing and able to undergo all testing procedures including neuroimaging and agree to longitudinal follow up Adequate visual and auditory acuity to allow neuropsychological testing Subjects with Clinical Dementia Rating Scale (CDR) of 0-0.5 Patients who are not demented Subjects sho signed an IRB approved informed consent prior to any study procedures Exclusion Criteria: Clinically significant hepatic, renal, pulmonary, metabolic, or endocrine disturbances as indicated by history, which in the opinion of the investigator might pose a potential safety risk to the subject Current clinically significant cardiovascular disease. History of drug or alcohol abuse within the last year, or prior prolonged history of abuse Clinically significant infections disease, including Acquired Immune Deficiency Syndrome (AIDS) or Human Immunodeficiency Virus (HIV) infection or previous positive test for hepatitis History of relevant severe drug allergy or hypersensitivity Received an investigational medication under an FDA IND protocol within the last 30 days. Current clinically significant unstable medical comorbidities, as indicated by history or physical exam, that pose a potential safety risk to the subject Received a radiopharmaceutical for imaging or therapy within the past 24 hours prior to the imaging session for this study Severe psychiatric disorders including schizophrenia, bipolar disorders, and major depression as described in DSM-IV within the past year (medical record, GDS score, interview with the patient and study partner) Obvious causes for their cognitive impairment (e.g. onset coincides with recent head trauma or stroke) Dementia of any cause CDR score > 0.5 Expressed the preference to undergo the procedure under regional anesthesia in form of spinal or epidural anesthesia Patients who, in the opinion of the investigator, are otherwise unsuitable for a study of this type
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marek Brzezinski, MD, PhD
Phone
877-487-2838
Email
brzezinm@anesthesia.ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marek Brzezinski, MD, PhD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
San Francisco VA Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94121
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marek Brzezinski, MD, PhD
First Name & Middle Initial & Last Name & Degree
Kim Hubert, MD, PhD
First Name & Middle Initial & Last Name & Degree
Carina Mari Aparici, MD
First Name & Middle Initial & Last Name & Degree
Michael Weiner, MD
First Name & Middle Initial & Last Name & Degree
John Kornak, PhD
First Name & Middle Initial & Last Name & Degree
Joel H Kramer, PsyD
First Name & Middle Initial & Last Name & Degree
Mervyn Maze, MB, ChB

12. IPD Sharing Statement

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Effects of Brain Beta-Amyloid on Postoperative Cognition

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