Effects of Brain Beta-Amyloid on Postoperative Cognition

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of California, San Francisco
Sponsor:
Collaborators:
Alzheimer’s Drug Discovery Foundation
Avid Radiopharmaceuticals
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01606488
First received: May 23, 2012
Last updated: April 15, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Postoperative Cognitive Dysfunction
Drug: Florbetapir F 18 (18F-AV-45)
Other: no intervention
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Effects of Brain Beta Amyloid on Postoperative Cognition and 18F-AV-45-A14: Clinical Evaluation of Florbetapir F 18 (18F-AV-45)

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Cognitive Decline [ Time Frame: At the time of discharge (or at the latest on the 7th postoperative day) ] [ Designated as safety issue: No ]
    Measured using comprehensive neurocognitive test battery


Secondary Outcome Measures:
  • Genetic Polymorphisms [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured by obtaining blood sample

  • Vagus nerve tone assessment [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using Heart Rate Variability (HRV)

  • Inflammatory Markers [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured by obtaining blood samples

  • Perioperative Complications [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: No ]
    Measured using patient medical records

  • Delirium [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: No ]
    Measured using the Confusion Assessment Method rating scale (CAM) or the CAM-ICU if admitted to the intensive care unit

  • Coma Assessment [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: No ]
    Measured using the Richmond Agitation Sedation Scale (RASS)

  • Hospital Length of Stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: No ]
    Measured using patient medical records

  • Postoperative Complications [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using patient medical records

  • Change in Cognition [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using comprehensive neurocognitive test battery

  • Quality of Life [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured by assessing functional status using the Functional Activities Questionnaire and depression using the Geriatric Depression Scale

  • Mortality [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using patient medical records

  • Pain intensity [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using the Numerical Rating Scale

  • Pain unpleasantness [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using the Numerical Rating Scale

  • Post-traumatic Stress Disorder symptomatology [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using the PTSD Checklist


Estimated Enrollment: 100
Study Start Date: May 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Surgical Group

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.

Drug: Florbetapir F 18 (18F-AV-45)
Single IV bolus injection of 370 MBq (10mCi) florbetapir will be administered approximately 50 minutes prior to a 10 minute PET scan.
Other Names:
  • Florbetapir
  • Amyvid 18F-AV-45
Non-surgical group

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.

Other: no intervention

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01606488

Contacts
Contact: Marek Brzezinski, MD, PhD 877-487-2838 brzezinm@anesthesia.ucsf.edu
Contact: Maren Gregersen 415-221-4810 ext 4385 gregersenm@anesthesia.ucsf.edu

Locations
United States, California
San Francisco VA Medical Center Recruiting
San Francisco, California, United States, 94121
Principal Investigator: Marek Brzezinski, MD, PhD         
Sub-Investigator: Kim Hubert, MD, PhD         
Sub-Investigator: Carina Mari Aparici, MD         
Sub-Investigator: Michael Weiner, MD         
Sub-Investigator: John Kornak, PhD         
Sub-Investigator: Joel H Kramer, PsyD         
Sub-Investigator: Mervyn Maze, MB, ChB         
Sponsors and Collaborators
University of California, San Francisco
Alzheimer’s Drug Discovery Foundation
Avid Radiopharmaceuticals
Investigators
Principal Investigator: Marek Brzezinski, MD, PhD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01606488     History of Changes
Other Study ID Numbers: 20110506, 18F-AV-45-A14
Study First Received: May 23, 2012
Last Updated: April 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
Postoperative Cognitive Dysfunction
Postoperative Cognitive Decline
POCD
Alzheimer's disease
Florbetapir F 18 (18F-AV-45)

Additional relevant MeSH terms:
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on July 28, 2014