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Blood Brain Barrier Dysfunction and Postoperative Neurocognitive Disorders (BBBSx)

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ClinicalTrials.gov Identifier: NCT04566562
Recruitment Status : Recruiting
First Posted : September 28, 2020
Last Update Posted : December 15, 2022
Sponsor:
Information provided by (Responsible Party):
Rajesh Kumar, PhD, University of California, Los Angeles

Study Description
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Brief Summary:

Postoperative neurocognitive disorders (PND), which include postoperative delirium and both acute and longlasting neurocognitive deficits, are a significant public health problem, leading to a cascade of deleterious complications. Older adults are particularly at-risk of developing PND both in the short and long term. Although age is consistently reported as an important risk factor, the exact pathophysiology of PND remains poorly understood, but may include postsurgery-compromised blood brain barrier (BBB) function. This project proposes that perioperative BBB dysfunction is associated with measurable brain morphologic findings in cognitive control areas that can be discovered with non-invasive magnetic resonance imaging (MRI). Patients scheduled for surgery with an age range of 65-75 years of age, will participate in brain diffusion-weighted pseudo-continuous arterial spin labeling (DW-pCASL) and diffusion tensor imaging (DTI), cognitive assessments, and evaluation of a BBB marker from blood (at baseline, at two weeks, and at six months after surgery).

All patients will have a brain scan (MRI) within before surgery and two weeks and six months after surgery. During this visit cognitive function will be assessed. Patients will also be asked to participate in a blood draw.


Condition or disease Intervention/treatment
Neurocognitive Disorders Postoperative Cognitive Dysfunction Diagnostic Test: Brain Imaging Diagnostic Test: Cognitive Testing Diagnostic Test: Blood Biomarkers

Detailed Description:

The investigators will examine the potential mechanisms contributing to PND in an older surgical population. It is proposed that BBB will be altered contributing to brain tissue changes in cognitive control areas that can be examined with MD measures and blood biomarkers. Therefore, the specific aims are to:

AIM #1: Examine BBB function, using DW-pCASL procedures, and BBB marker (S100β levels), in older adult subjects between pre- ) and post-surgery

AIM #2: Assess brain tissue changes, using DTI-based MD measures, and cognition function, between pre- and post-surgery in older adult subjects.

AIM #3: Examine the relationships between BBB blood biomarker, BBB function index, and MD values from cognitive control areas (prefrontal cortex, caudate, and hippocampus) between pre- and post-surgery in an older surgical population.

A One-group comparative and longitudinal study design will be used in this proposal. A total of 34 older subjects scheduled for surgery will be recruited. Patients of either sex, in the age range 65-75 years scheduled for abdominal, gynecologic or urologic.

To assess cognitive function, the WRAML2 and MoCA tests will be performed within one week before surgery and at two weeks and six months after surgery. These tests have been used by our team in several conditions, and will be introduced just before MRI procedures. An average mean score of 100±15 on WRAML2 and a score ≥26 on MoCA will be considered normal.

Examination of BBB integrity from blood. To account for interindividual variation, baseline systemic biomarkers will be measured preoperatively (within one week before surgery). Postoperative samples will also be collected at two weeks and 6 months of surgery. Samples will be batch analyzed using Enzyme-linked immunosorbent assay (S100β) by the UCLA Department of Pathology & Laboratory Medicine.

Magnetic Resonance Imaging. All brain MRI studies will be performed on a 3.0-Tesla MRI scanner (Siemens, Magnetom, Prisma) at the Department of Radiology, UCLA. MRI studies will be performed within one week before surgery, and at two weeks and six months after surgery.

Study Design
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Study Type : Observational
Estimated Enrollment : 34 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Blood Brain Barrier Dysfunction and Postoperative Neurocognitive Disorders in Older Adults
Actual Study Start Date : August 3, 2020
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : July 31, 2023
Groups and Cohorts
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Group/Cohort Intervention/treatment
Study Group
Brain scans, cognitive tests, blood biomarkers
 Diagnostic Test: Brain Imaging
Magnetic Resonance Imaging (MRI) using diffusion weighted pseudo-continuous arterial spin labeling (DW-pCASL) .

Diagnostic Test: Cognitive Testing
Wide Range Assessment of Memory and Learning (WRAML 2) and Montreal Cognitive Assessment (MoCA)

Diagnostic Test: Blood Biomarkers
Inflammatory Markers


Outcome Measures
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Primary Outcome Measures :
  1. Preoperative cognitive function [ Time Frame: pre-surgery (within five days before) ]
    Montreal Cognitive Assessment (MoCA) test

  2. Postoperative cognitive dysfunction - delayed cognitive recovery [ Time Frame: Post-surgery (within two weeks post surgery) ]
    Montreal Cognitive Assessment (MoCA) test

  3. Postoperative cognitive dysfunction - neurocognitive disorder [ Time Frame: Post-surgery (6 months after surgery) ]
    Montreal Cognitive Assessment (MoCA) test

  4. Preoperative cognitive function II [ Time Frame: Pre-surgery (within five days before surgery) ]
    Wide Range Assessment of Memory and Learning (WRAML2)

  5. Postoperative cognitive dysfunction - delayed cognitive recovery II [ Time Frame: Post-surgery (within two weeks post surgery) ]
    Wide Range Assessment of Memory and Learning (WRAML2)

  6. Postoperative cognitive dysfunction - neurocognitive disorder II [ Time Frame: Post-surgery (6 months after surgery) ]
    Assessment of Memory and Learning (WRAML2)


Secondary Outcome Measures :
  1. Blood Serum anti-inflammatory Biomarkers [ Time Frame: pre- (within five days before surgery) ]
    Assess blood inflammatory biomarkers (IL6, TNFa and IL1B) using enzyme-linked immunosorbent assay

  2. Blood Serum anti-inflammatory Biomarkers II [ Time Frame: post-surgery (within two weeks of surgery) ]
    Assess blood inflammatory biomarkers (IL6, TNFa and IL1B) using enzyme-linked immunosorbent assay

  3. Brain changes [ Time Frame: pre- surgery (within five days before) ]
    Using non-invasive magnetic resonance imaging diffusion weighted (DW) pseudo-continuous arterial spin labeling (pCASL)

  4. Brain changes II [ Time Frame: Post-surgery (within two days post surgery) ]
    non-invasive magnetic resonance imaging diffusion weighted (DW) pseudo-continuous arterial spin labeling (pCASL)

  5. Brain changes III [ Time Frame: Post-surgery (within six months post surgery) ]
    Using non-invasive magnetic resonance imaging diffusion weighted (DW) pseudo-continuous arterial spin labeling (pCASL)


Eligibility Criteria
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Ages Eligible for Study:   65 Years to 75 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients of either sex, in the age range 65-75 years scheduled for abdominal, gynecologic or urologic surgery.
Criteria

Inclusion Criteria:

  • 65-75 years old
  • Scheduled for abdominal, gynecologic or urological surgery

Exclusion Criteria:

  • Subjects undergoing surgery with a previous history of stroke, myocardial infarction, current pregnancy (if female), diagnosed neuropsychological and neuropsychiatric diseases, airway or chest deformities that would interfere with breathing, chronic obstructive pulmonary disease, cystic fibrosis, presence of space-occupying brain lesions, any history of drug abuse (e.g., cocaine or tobacco use), chronic kidney disease requiring dialysis.
  • Body weight >300 pounds (restrictions of MRI scanner table).
  • All subjects with any contraindication to the MRI procedures, such as metallic and electronic implants (phrenic or cardiac pacemakers), claustrophobia, metallic-based tattoos, will also be excluded. Non-english speaking patients will also be excluded as the cognitive tests have not been validated in other languages.
Contacts and Locations
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04566562


Contacts
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Contact: Stephanie-Dee Sarovich 310.206.4484 ssarovich@mednet.ucla.edu
Contact: Jennifer Scovotti, MA 310.206.4484 jscovotti@mednet.ucla.edu

Locations
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United States, California
Ronald Reagan UCLA Medical Center, Department of Anesthesiology & Perioperative Medicine Recruiting
Los Angeles, California, United States, 90095
Contact: Stephanie-Dee Sarovich    310-206-4484    ssarovich@mednet.ucla.edu   
Contact: Jennifer Scovotti, MA    310.206.4484    jscovotti@mednet.ucla.edu   
Principal Investigator: Rajesh Kumar, PhD         
Sponsors and Collaborators
University of California, Los Angeles
Investigators
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Principal Investigator: Rajesh Kumar, Ph.D rkumar@mednet.ucla.edu
Principal Investigator: Susana Vacas, M.D., Ph.D. Massachusetts General Hospital
More Information
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Responsible Party: Rajesh Kumar, PhD, Professor In-Residence, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT04566562    
Other Study ID Numbers: BBBSx 20-001456
First Posted: September 28, 2020    Key Record Dates
Last Update Posted: December 15, 2022
Last Verified: December 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rajesh Kumar, PhD, University of California, Los Angeles:
brain imaging, neurocognitive testing
Additional relevant MeSH terms:
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Postoperative Cognitive Complications
Cognitive Dysfunction
Neurocognitive Disorders
Pathologic Processes
 Cognition Disorders
Mental Disorders
Postoperative Complications