Effects of Brain Beta-Amyloid on Postoperative Cognition

Sponsor

University of California, San Francisco (Other)

Overall Status

Recruiting

CT.gov ID

NCT01606488

Collaborator

Alzheimer's Drug Discovery Foundation (Other), Avid Radiopharmaceuticals (Industry)

100

Enrollment

Location

Arms

121

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

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.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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)

Study Start Date :

May 1, 2012

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Other: 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
Other: 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

Arm

Intervention/Treatment

Other: 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

Other: 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

Outcome Measures

Primary Outcome Measures

Cognitive Decline [At the time of discharge (or at the latest on the 7th postoperative day)]
Measured using comprehensive neurocognitive test battery

Secondary Outcome Measures

Genetic Polymorphisms [Participants will be followed from preoperative baseline to 1 year postoperative]
Measured by obtaining blood sample
Vagus nerve tone assessment [Participants will be followed from preoperative baseline to 1 year postoperative]
Measured using Heart Rate Variability (HRV)
Inflammatory Markers [Participants will be followed from preoperative baseline to 1 year postoperative]
Measured by obtaining blood samples
Perioperative Complications [Participants will be followed for the duration of hospital stay, an expected average of 1 week]
Measured using patient medical records
Delirium [Participants will be followed for the duration of hospital stay, an expected average of 1 week]
Measured using the Confusion Assessment Method rating scale (CAM) or the CAM-ICU if admitted to the intensive care unit
Coma Assessment [Participants will be followed for the duration of hospital stay, an expected average of 1 week]
Measured using the Richmond Agitation Sedation Scale (RASS)
Hospital Length of Stay [Participants will be followed for the duration of hospital stay, an expected average of 1 week]
Measured using patient medical records
Postoperative Complications [Participants will be followed from preoperative baseline to 1 year postoperative]
Measured using patient medical records
Change in Cognition [Participants will be followed from preoperative baseline to 1 year postoperative]
Measured using comprehensive neurocognitive test battery
Quality of Life [Participants will be followed from preoperative baseline to 1 year postoperative]
Measured by assessing functional status using the Functional Activities Questionnaire and depression using the Geriatric Depression Scale
Mortality [Participants will be followed from preoperative baseline to 1 year postoperative]
Measured using patient medical records
Pain intensity [Participants will be followed from preoperative baseline to 1 year postoperative]
Measured using the Numerical Rating Scale
Pain unpleasantness [Participants will be followed from preoperative baseline to 1 year postoperative]
Measured using the Numerical Rating Scale
Post-traumatic Stress Disorder symptomatology [Participants will be followed from preoperative baseline to 1 year postoperative]
Measured using the PTSD Checklist

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts 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