Effects of Brain Beta-Amyloid on Postoperative Cognition

NCT01606488 | Active Not Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2011050618F-AV-45-A14
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Postoperative Cognitive Dysfunction

Keywords

Postoperative Cognitive Dysfunction; Postoperative Cognitive Decline; POCD; Alzheimer's disease; Florbetapir F 18 (18F-AV-45)

Outcome Measures

Primary Outcomes (1)

• Cognitive Decline

  Measured using comprehensive neurocognitive test battery

  At the time of discharge (or at the latest on the 7th postoperative day)

Secondary Outcomes (14)

• Genetic Polymorphisms

  Participants will be followed from preoperative baseline to 1 year postoperative

• Vagus nerve tone assessment

  Participants will be followed from preoperative baseline to 1 year postoperative

• Inflammatory Markers

  Participants will be followed from preoperative baseline to 1 year postoperative

• Perioperative Complications

  Participants will be followed for the duration of hospital stay, an expected average of 1 week

• Delirium

  Participants will be followed for the duration of hospital stay, an expected average of 1 week

Study Arms (2)

Surgical Group

OTHER

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)

Non-surgical group

OTHER

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

Interventions

Florbetapir F 18 (18F-AV-45) DRUG

Single IV bolus injection of 370 MBq (10mCi) florbetapir will be administered approximately 50 minutes prior to a 10 minute PET scan.

Also known as: Florbetapir, Amyvid 18F-AV-45

Surgical Group

no intervention OTHER

Non-surgical group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Alzheimer's Drug Discovery Foundation: collaborator
• Avid Radiopharmaceuticals: collaborator

Study Sites (1)

San Francisco VA Medical Center

San Francisco, California, 94121, United States

Location

MeSH Terms

Conditions

Postoperative Cognitive Complications; Alzheimer Disease

Interventions

florbetapir

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Officials

• Marek Brzezinski, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2012
• First Posted: May 25, 2012
• Study Start: May 1, 2012
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)