Brain Beta-Amyloid for Postoperative Cognitive Dysfunction

Overseen By Marek Brzezinski, MD, PhD

Age: 65+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Disqualifiers: Cardiovascular disease, Severe psychiatric disorders, Dementia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether beta-amyloid plaques (protein deposits often linked to Alzheimer's) in the brain before surgery can predict cognitive decline after hip or knee replacement in older adults. It includes two groups: one undergoing surgery, receiving a special brain scan with Florbetapir F 18 (a diagnostic imaging agent) and various assessments, and another with similar joint pain but not undergoing surgery, who will also receive assessments. Ideal participants are those planning hip or knee replacement surgery, able to speak English, and living with someone who can report on their cognitive status. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, aiming to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What is the safety track record for Florbetapir F 18 (18F-AV-45)?

Research has shown that florbetapir F 18, the treatment being tested in this study, has undergone thorough safety checks. It has been studied in many people and already holds FDA approval for other uses, indicating general safety when used correctly.

However, due to the small amount of radiation involved, specific safety steps must be followed to minimize radiation exposure. These precautions are standard for this type of imaging agent. Overall, evidence indicates that florbetapir F 18 is safe for use in clinical settings. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Florbetapir F 18 (18F-AV-45) because it offers a new way to address postoperative cognitive dysfunction (POCD), which is a common issue after surgeries like knee or hip replacements. Unlike standard treatments, which often focus on managing symptoms with cognitive and physical therapy, Florbetapir F 18 uses a PET scan to visualize brain beta-amyloid plaques, potentially identifying those at risk for POCD before surgery. This approach could lead to more personalized interventions, aiming to prevent cognitive issues rather than simply treating them after they occur. The ability to identify at-risk patients through imaging is what makes this approach particularly unique and promising.

What evidence suggests that this trial's treatment could be effective for postoperative cognitive decline?

Research shows that Florbetapir F 18 has been used safely in over 2,000 people. This imaging agent helps identify beta-amyloid plaques in the brain. In this trial, participants in the Surgical Group will undergo the florbetapir PET scan to assess these plaques before surgery. Some studies suggest that a higher presence of these plaques might increase the risk of memory and thinking problems post-surgery. However, other studies found that these plaques don't always predict who will experience these issues. While the predictive ability of this imaging for cognitive decline is still under investigation, it remains a valuable tool for understanding brain changes related to aging and surgery. ^{3 6 7 8 9}

Who Is on the Research Team?

Marek Brzezinski, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 65 or older with mild cognitive issues, scheduled for knee or hip replacement surgery under general anesthesia. They must have someone to report on their cognition, be able to undergo tests including brain scans, and not expect post-surgery intubation. Excluded are those with significant heart disease, unstable conditions, recent radiopharmaceutical use, substance abuse history, severe allergies or infections like HIV/AIDS or hepatitis.

Inclusion Criteria

I am not expected to need a breathing tube after surgery.

Subjects with Clinical Dementia Rating Scale (CDR) of 0-0.5

I can see and hear well enough for brain function tests.

Exclusion Criteria

CDR score > 0.5

I haven't had any radiopharmaceuticals for imaging or therapy in the last 24 hours.

History of relevant severe drug allergy or hypersensitivity

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Assessment

Participants undergo florbetapir PET scan and baseline neurocognitive assessments

1 week

1 visit (in-person)

Surgery and Immediate Postoperative

Participants undergo surgery and are monitored for cognitive decline and other complications

1 week

Daily monitoring during hospital stay

Follow-up

Participants are monitored for cognitive decline, quality of life, and other outcomes

1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Florbetapir F 18 (18F-AV-45)

Trial Overview The study examines if the presence of beta-amyloid plaques in the brain before surgery can predict worsening of mental functions after surgery in elderly patients undergoing hip or knee replacements. It involves no direct intervention but uses a tracer called Florbetapir F 18 during brain imaging to detect these plaques.

How Is the Trial Designed?

Group I: Surgical Group Experimental Treatment 1 Intervention

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.

Group II: Non-surgical group Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Alzheimer's Drug Discovery Foundation

Collaborator

Trials

22

Recruited

3,100+

Avid Radiopharmaceuticals

Industry Sponsor

Trials

66

Recruited

9,700+

Dr. Daniel M. Skovronsky

Avid Radiopharmaceuticals

Chief Executive Officer since 2004

MD and PhD in Neuroscience from the University of Pennsylvania

Dr. Adam S. Fleisher

Avid Radiopharmaceuticals

Chief Medical Officer since 2022

MD, MAS

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5849499/

18F-florbetapir PET-determined Cerebral β-Amyloid ... We hypothesized that 6-week 18F-florbetapir cortical amyloid burden would be greater in those patients manifesting postoperative cognitive dysfunction at 6 ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT01606488

Effects of Brain Beta-Amyloid on Postoperative Cognition Summary. Postoperative cognitive decline (POCD) affects up to 50% of non-cardiac surgical patients greater than or equal to 65 years of age.

3. withpower.com withpower.com/trial/phase-4-postoperative-cognitive-complications-4-2012-06606

Brain Beta-Amyloid for Postoperative Cognitive Dysfunction Florbetapir F 18 has been well-tolerated in studies involving more than 2000 human subjects, with no significant safety concerns reported.

4. researchgate.net researchgate.net/publication/322872698_18F-florbetapir_Positron_Emission_Tomography-determined_Cerebral_b-Amyloid_Deposition_and_Neurocognitive_Performance_after_Cardiac_Surgery

(PDF) 18F-florbetapir Positron Emission Tomography ... Results: The authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29389750/

18F-florbetapir Positron Emission Tomography-determined ... Results: The authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) at 6 weeks ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/202008s046lbl.pdf

AMYVID (florbetapir F 18 injection), for intravenous use Handle AMYVID with appropriate safety measures to minimize radiation exposure during administration [see Warnings and Precautions (5.2)]. Use waterproof gloves ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3780320/

Cortical β-amyloid levels and neurocognitive performance ... We chose 18F-florbetapir because: (1) it is the only tracer that has completed phase 2 and phase 3 studies; (2) it has safety data from a large ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0883944117303945

Florbetapir-PET β-amyloid imaging and associated ... Data suggest that a significant percentage of patients will experience marked cognitive impairment after critical illness [3], [4], [5], [6], [7], yet questions ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01518374

Clinical Evaluation of Florbetapir F 18 (18F-AV-45) This protocol is designed to standardize imaging studies using florbetapir F 18 PET to provide information on amyloid burden in subjects participating in ...